WorldWideScience

Sample records for cells initial evaluation

  1. Pulmonary langerhans cell histiocytosis: PET/CT for initial workup and treatment response evaluation.

    Science.gov (United States)

    Hansen, Neil J; Hankins, Jordan H

    2015-02-01

    A 40-year-old man underwent pan-endoscopy owing to abdominal pain. Biopsies of the gastrointestinal tract demonstrated diffuse Langerhans cell histiocytosis. PET/CT was done, with CT demonstrating classic pulmonary manifestations of Langerhans cell histiocytosis that had association with intense FDG uptake on PET. Bowel appeared normal. Treatment was initiated with smoking cessation and 6 cycles of cytarabine. Follow-up PET/CT after initial treatment demonstrated improvement of parenchymal abnormalities seen on CT, with resolution of hypermetabolic activity. Maintenance chemotherapy was initiated. PET/CT is increasingly being used for initial staging and treatment response assessment in this rare disorder. PMID:24999688

  2. Evaluation and Evaluating the Community Initiative "URBAN"

    DEFF Research Database (Denmark)

    Alves, Sonia

    2013-01-01

    greater focus on a more open and democratic process of evaluation. This paper presents and compares different conceptual and methodological frameworks created for the assessment of the European initiative Urban II, including the one that was used by the author in the context of an academic evaluation in...

  3. Teaching Evaluation: Waiting for Initiatives

    Directory of Open Access Journals (Sweden)

    Alejandro Canales Sánchez

    2008-08-01

    Full Text Available In this text, it is sustained that, despite the fact that the teaching activity is one of the main functions of higher education institutions or even the only one in most of them, it hasn’t been reflected in the leading initiatives that have been set in motion in this area for the last two decades. In particular, it points out that the wide evaluation politics established in the education system during the late eighties, didn’t consider the teaching activity as a concern issue for the mechanisms or rewards in the evaluation system. Even though the implementation of new actions tried to repair the situation, mainly by improving the quality of working time and the qualifications of the personnel performing these activities; teaching, in strict sense, and the design or application of a new evaluation scheme to strengthen it, didn’t get better.

  4. Evaluation of commercial lithium-ion cells based on composite positive electrode for plug-in hybrid electric vehicle applications. Part I: Initial characterizations

    International Nuclear Information System (INIS)

    Evaluating commercial Li-ion batteries presents some unique benefits. One of them is to use cells made from established fabrication process and form factor, such as those offered by the 18650 cylindrical configuration, to provide a common platform to investigate and understand performance deficiency and aging mechanism of target chemistry. Such an approach shall afford us to derive relevant information without influence from processing or form factor variability that may skew our understanding on cell-level issues. A series of 1.9 Ah 18650 lithium ion cells developed by a commercial source using a composite positive electrode comprising (LiMn1/3Ni1/3Co1/3O2 + LiMn2O4) is being used as a platform for the investigation of certain key issues, particularly path-dependent aging and degradation in future plug-in hybrid electric vehicle (PHEV) applications, under the US Department of Energy's Applied Battery Research (ABR) program. Here we report in Part I the initial characterizations of the cell performance and Part II some aspects of cell degradation in 2C cycle aging. The initial characterizations, including cell-to-cell variability, are essential for life cycle performance characterization in the second part of the report when cell-aging phenomena are discussed. Due to the composite nature of the positive electrode, the features (or signature) derived from the incremental capacity (IC) of the cell appear rather complex. In this work, the method to index the observed IC peaks is discussed. Being able to index the IC signature in details is critical for analyzing and identifying degradation mechanism later in the cycle aging study.

  5. Framework for Evaluation of Equity Initiatives

    Science.gov (United States)

    Bexley, Emmaline; Harris, Kerri-Lee; James, Richard

    2010-01-01

    The Framework for Evaluation of Equity Initiatives has been prepared to support the Go8 Equity Strategy. Its purpose is to assist Group of Eight (Go8) universities to evaluate the effectiveness of their equity initiatives and interventions in the context of federal policies and the distinctive missions and responsibilities of the individual Go8…

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

    Science.gov (United States)

    Harkness, J. D.

    1975-01-01

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

  7. Metastasis-Initiating Cells in Renal Cancer

    OpenAIRE

    Khan, Mohammed I.; Czarnecka, Anna M; Duchnowska, Renata; Kukwa, Wojciech; Szczylik, Cezary

    2013-01-01

    Metastasis is a complex process that propagates cells from the primary or initial site of the cancer occurrence to distant parts of the body. Cancer cells break from the cancer site and circulate through the bloodstream or lymph vessels, allowing them to reach nearly all parts of the body. These circulating tumour cells (CTCs) contain specialized metastasis-initiating cells (MICs) that reside in the biological heterogeneous primary tumour. Researchers have hypothesized that metastasis of rena...

  8. Evaluating the Bush Climate Change Initiative

    NARCIS (Netherlands)

    Moor APG de; Berk MM; Elzen MGJ den; Vuuren DP van; MNV

    2002-01-01

    This report evaluates the Climate Change Initiative as presented by President Bush on February 14, 2002. The President's proposal aims to reduce the greenhouse gas intensity of the US economy by 18 per cent between 2002 and 2012. This policy target can be regarded as being very modest, when compared

  9. Subcutaneous panniculitis-like T-cell lymphoma in a child: whole-body MRI in the initial and follow-up evaluations

    International Nuclear Information System (INIS)

    Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is classified as an unusual subtype of peripheral T-cell lymphoma that preferentially infiltrates the subcutaneous tissue without overt lymph node involvement. SPTCL is particularly rare in children, and there have been only a few case reports describing the US and CT findings of SPTCL. To our knowledge, the use of whole-body (WB) MRI as the initial and follow-up diagnostic method to assess the extent of disease and relapse of SPTCL has not been reported in children. In our case report involving one child, WB MRI was useful as both the initial and follow-up diagnostic method to assess the extent of disease and to monitor the patient's response to therapy for SPTCL. (orig.)

  10. Evaluation program for secondary spacecraft cells: Initial evaluation tests of General Electric Company 40.0 ampere-hour nickel-cadmium spacecraft cells for the tracking data relay satellite system

    Science.gov (United States)

    Harkness, J. D.

    1978-01-01

    Five cells provided by NASA's Goddard Space Flight Center were evaluated at room temperature and pressure (25 C plus or minus 2 C) with discharges at the 2 hour rate. Measurements of the cell containers following test, indicated an average increase of .006 inches at the plate thickness. Average end of charge voltages and pressures, and capacity output in ampere hours were determined. Three cells exceeded the voltage requirements of 1.52 volts during both c/10 charges at 20 C. All cells exceeded the voltage requirement of 1.52 volts during the 0 C overcharge test, although their end charges were below 1.50 volts. The pressure requirement of 65 psia was exceeded by both pressure transducer cells during c/10 charges at 25 C and 20 C and also during the 0 C overcharge test. The cells with pressure transducers reached a pressure of 20 psia before reaching the voltage limit of 1.550 volts during the pressure versus capacity test, and exhibited a pressure decay of 2 psia during the last 30 minutes of the 1 hour open circuit stand. Average capacity was 51.3 ampere hours.

  11. Prostate cancer and metastasis initiating stem cells

    Institute of Scientific and Technical Information of China (English)

    Kathleen Kelly; Juan Juan Yin

    2008-01-01

    Androgen refractory prostate cancer metastasis is a major clinical challenge.Mechanism-based approaches to treating prostate cancer metastasis require an understanding of the developmental origin of the metastasis-initiating cell.Properties of prostate cancer metastases such as plasticity with respect to differentiated phenotype and androgen independence are consistent with the transformation of a prostate epithelial progenitor or stem cell leading to metastasis.This review focuses upon current evidence and concepts addressing the identification and properties of normal prostate stem or progenitor cells and their transformed counterparts.

  12. Effects of Recombinant Erythropoietin on Breast Cancer-Initiating Cells

    OpenAIRE

    Tiffany M. Phillips; Kwanghee Kim; Erina Vlashi; McBride, William H.; Frank Pajonk

    2007-01-01

    BACKGROUND: Cancer anemia causes fatigue and correlates with poor treatment outcome. Erythropoietin has been introduced in an attempt to correct these defects. However, five recent clinical trials reported a negative impact of erythropoietin on survival and/or tumor control, indicating that experimental evaluation of a possible direct effect of erythropoietin on cancer cells is required. Cancer recurrence is thought to rely on the proliferation of cancer initiating cells (CICs). In breast can...

  13. Systematic evaluation program. Status report and initial evaluation

    International Nuclear Information System (INIS)

    The MHB Ongoing Systematic Evaluation Program (SEP) Assessment Study was initiated by the Swedish Nuclear Power Inspectorate (SKI) in 1980. This MHB report is a status report and initial evaluation of SEP. The methodology and results of SEP are disscused with particular emphasis on the first two SEP plant reviews - the Palisades and R.E. Ginna nuclear power plants. The comments of cognizant persons in the NRC and the ACRS, as well as private consultants, are included herein. MHBs major findings are as follows: The SEP plant review methodology was acceptable to the NRC Commissioners, the ACRS, and the NRC Staffs consultants who evaluated the first two SEP plant reviews. A concern raised by all who commented on SEP was the absence of Three Mile Island Action Plan Items and Unresolved Safety Issues from current SEP reviews. The SEP reviews of the Palisades and R.E. Ginna plants concluded that the two plant designs were adequate with respect to a majority of safety topics. Several topics remain unresolved in both the Palisades and R.E. Ginna SEP reviews. In the case of the Ginna plant, several related topics have been grouped together in a major structural reevaluation study. In general, due to the number of unresolved and excluded topics, SEP has not at this time produced a plant safety evaluation which can be considered complete and integrated. (author)

  14. Initial evaluation of automated treatment planning software.

    Science.gov (United States)

    Gintz, Dawn; Latifi, Kujtim; Caudell, Jimmy; Nelms, Benjamin; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

    2016-01-01

    Even with advanced inverse-planning techniques, radiation treatment plan opti-mization remains a very time-consuming task with great output variability, which prompted the development of more automated approaches. One commercially available technique mimics the actions of experienced human operators to pro-gressively guide the traditional optimization process with automatically created regions of interest and associated dose-volume objectives. We report on the initial evaluation of this algorithm on 10 challenging cases of locoreginally advanced head and neck cancer. All patients were treated with VMAT to 70 Gy to the gross disease and 56 Gy to the elective bilateral nodes. The results of post-treatment autoplanning (AP) were compared to the original human-driven plans (HDP). We used an objective scoring system based on defining a collection of specific dosimetric metrics and corresponding numeric score functions for each. Five AP techniques with different input dose goals were applied to all patients. The best of them averaged the composite score 8% lower than the HDP, across the patient population. The difference in median values was statistically significant at the 95% confidence level (Wilcoxon paired signed-rank test p = 0.027). This result reflects the premium the institution places on dose homogeneity, which was consistently higher with the HDPs. The OAR sparing was consistently better with the APs, the differences reaching statistical significance for the mean doses to the parotid glands (p < 0.001) and the inferior pharyngeal constrictor (p = 0.016), as well as for the maximum doses to the spinal cord (p = 0.018) and brainstem (p = 0.040). If one is prepared to accept less stringent dose homogeneity criteria from the RTOG 1016 protocol, nine APs would comply with the protocol, while providing lower OAR doses than the HDPs. Overall, AP is a promising clinical tool, but it could benefit from a better process for shifting the balance between the target dose

  15. Proliferation resistance: issues, initiatives and evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Pilat, Joseph F [Los Alamos National Laboratory

    2009-01-01

    The vision of a nuclear renaissance has highlighted the issue of proliferation resistance. The prospects for a dramatic growth in nuclear power may depend on the effectiveness of, and the resources devoted to, plans to develop and implement technologies and approaches that strengthen proliferation resistance. The GenIV International Forum (GIF) and others have devoted attention and resources to proliferation resistance. However, the hope of finding a way to make the peaceful uses of nuclear energy resistant to proliferation has reappeared again and again in the history of nuclear power with little practical consequence. The concept of proliferation resistance has usually focused on intrinsic (technological) as opposed to extrinsic (institutional) factors. However, if there are benefits that may yet be realized from reactors and other facilities designed to minimize proliferation risks, it is their coupling with effective safeguards and other nonproliferation measures that likely will be critical. Proliferation resistance has also traditionally been applied only to state threats. Although there are no technologies that can wholly eliminate the risk of proliferation by a determined state, technology can play a limited role in reducing state threats and perhaps in eliminating many non-state threats. These and other issues are not academic. They affect efforts to evaluate proliferation resistance, including the methodology developed by GIF's Proliferation Resistance and Physical Protection (PR&PP) Working Group as well as the proliferation resistance initiatives that are being pursued or may be developed in the future. This paper will offer a new framework for thinking about proliferation resistance issues, including the ways the output of the methodology could be developed to inform the decisions that states, the International Atomic Energy (IAEA) and others will have to make in order to fully realize the promise of a nuclear renaissance.

  16. Employer engagement initiative evaluation: Main report

    OpenAIRE

    Johnston, Brenda; Fuller, Alison

    2011-01-01

    The Employer Engagement Initiative (EEI) at the University of Southampton aimed to increase the coherence of the University’s approach to employer engagement, especially its ability to offer flexible education at postgraduate level in the shape of work-based learning (WBL), online/e-learning and flexible programmes. In doing this, the Initiative sought to facilitate employee learning, address employer needs, and contribute to the long-term development of the University in line wit...

  17. Evaluation program for secondary spacecraft cells: Initial evaluation tests of General Electric Company 40.0 ampere hour nickel cadmium spacecraft cells for the tracking data relay satellite system

    Science.gov (United States)

    Hall, S. W.

    1980-01-01

    Average end of charge voltages and pressures, and capacity output in ampere hours are presented. Test limits specify those values at which a cell is to be terminated from charge or discharge. Requirements are based on past cell performance data. The requirement does not constitute a limit for discontinuance from testing. The nickel cadmium batteries were screened for internal shorts, low capacity, electrolyte leakage, or inability of any cell to recover its open circuit voltage above 1.150 volts during the internal short test.

  18. Evaluating the Bush Climate Change Initiative

    NARCIS (Netherlands)

    Moor APG de; Berk MM; Elzen MGJ den; Vuuren DP van; MNV

    2002-01-01

    Deze rapportage evalueert het Climate Change Initiative dat President Bush op 14 februari 2002 heeft gepresenteerd. Dit Initiatief beoogt de broeikasgasintensiteit van de Amerikaanse economie tussen 2002 en 2012 met 18 procent te verminderen. Deze beleidsambitie valt als zeer bescheiden te typer

  19. Fusion with stem cell makes the hepatocellular carcinoma cells similar to liver tumor-initiating cells

    OpenAIRE

    Wang, Ran; Chen, Shuxun; Li, Changxian; Ng, Kevin Tak Pan; Kong, Chi-Wing; Cheng, Jinping; Cheng, Shuk Han; Li, Ronald A.; Lo, Chung Mau; Man, Kwan; Sun, Dong

    2016-01-01

    Background Cell fusion is a fast and highly efficient technique for cells to acquire new properties. The fusion of somatic cells with stem cells can reprogram somatic cells to a pluripotent state. Our research on the fusion of stem cells and cancer cells demonstrates that the fused cells can exhibit stemness and cancer cell-like characteristics. Thus, tumor-initiating cell-like cells are generated. Methods We employed laser-induced single-cell fusion technique to fuse the hepatocellular carci...

  20. Open Access Initiatives in India - an Evaluation

    OpenAIRE

    Leila Fernandez

    2006-01-01

    Developing countries have embraced open access with a view to promoting visibility of research done in these regions. Open access initiatives described in this paper are based on interviews with information professionals responsible for creation and maintenance of online research repositories in India. Open access journals, e-print archives and e-theses repositories are covered with an emphasis on the sciences including the physical sciences, mathematics and the biomedical sciences. Existing ...

  1. Initial evaluation of the use of USPIO cell labeling and noninvasive MR monitoring of human tissue-engineered vascular grafts in vivo

    OpenAIRE

    Nelson, G. N.; Roh, J. D.; Mirensky, T. L.; Y Wang; Yi, T.; Tellides, G.; Pober, J S; Shkarin, P.; Shapiro, E. M.; Saltzman, W M; Papademetris, X.; Fahmy, T. M.; Breuer, C.K.

    2008-01-01

    This pilot study examines noninvasive MR monitoring of tissue-engineered vascular grafts (TEVGs) in vivo using cells labeled with iron oxide nanoparticles. Human aortic smooth muscle cells (hASMCs) were labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. The labeled hASMCs, along with human aortic endothelial cells, were incorporated into eight TEVGs and were then surgically implanted as aortic interposition grafts in a C.B-17 SCID/bg mouse host. USPIO-labeled hASMCs p...

  2. JOA Back Pain Evaluation Questionnaire: initial report

    OpenAIRE

    ,; Fukui, Mitsuru; Chiba, Kazuhiro; Kawakami, Mamoru; Kikuchi, Shinichi; Konno, Shinichi; Miyamoto, Masabumi; Seichi, Atsushi; Shimamura, Tadashi; Shirado, Osamu; Taguchi, Toshihiko; Takahashi, Kazuhisa; Takeshita, Katsushi; Tani, Toshikazu; Toyama, Yoshiaki

    2007-01-01

    Background There is no widely accepted objective evaluation for lumbar spine disorders. New outcome measures should be patient-oriented and should measure symptoms and self-reported functional status in multiple dimensions. The aim of this study was to identify items to be included in the disease-specific quality of life (QOL) questionnaire for the assessments of patients with lumbar spine disorders. Methods The draft of the QOL questionnaire that consisted of a total of 60 items, including 2...

  3. 40 CFR 8.7 - Initial environmental evaluation.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Initial environmental evaluation. 8.7 Section 8.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL ENVIRONMENTAL IMPACT ASSESSMENT OF NONGOVERNMENTAL ACTIVITIES IN ANTARCTICA § 8.7 Initial environmental evaluation. (a)...

  4. 45 CFR 641.17 - Initial environmental evaluation.

    Science.gov (United States)

    2010-10-01

    ... transitory impact on the Antarctic environment, no further environmental review of the action is necessary... 45 Public Welfare 3 2010-10-01 2010-10-01 false Initial environmental evaluation. 641.17 Section... Initial environmental evaluation. (a) Contents. An IEE shall contain sufficient detail to assess whether...

  5. Open Access Initiatives in India - an Evaluation

    Directory of Open Access Journals (Sweden)

    Leila Fernandez

    2006-03-01

    Full Text Available Developing countries have embraced open access with a view to promoting visibility of research done in these regions. Open access initiatives described in this paper are based on interviews with information professionals responsible for creation and maintenance of online research repositories in India. Open access journals, e-print archives and e-theses repositories are covered with an emphasis on the sciences including the physical sciences, mathematics and the biomedical sciences. Existing repositories were identified from the Registry of Open Access Repositories located at http://archives.eprints.org. Key contacts were facilitated by well-known local open access advocates. Participants were contacted by e-mail and sites visited wherever possible. Many universities in India are at present lacking in infrastructure for establishing institutional repositories, so most of the institutions visited were research institutes and informatics centres. Semi-structured interviews were conducted to ascertain the background of participants, institutional culture, software selection, nature of funding, submission policies and future plans of these repositories. Also covered were promotion methods, user feedback and institutional support. Barriers to setting up institutional repositories are identified in this paper. Special features are described. Based on participant feedback a list of best practices is presented. The study has definite implications for the role of Canadian librarians in the promotion of Canadian research.

  6. Initial evaluation of the "Trauma surgery course"

    Directory of Open Access Journals (Sweden)

    Tugnoli Gregorio

    2006-03-01

    Full Text Available Abstract Background The consequence of the low rate of penetrating injuries in Europe and the increase in non-operative management of blunt trauma is a decrease in surgeons' confidence in managing traumatic injuries has led to the need for new didactic tools. The aim of this retrospective study was to present the Corso di Chirurgia del Politrauma (Trauma Surgery Course, developed as a model for teaching operative trauma techniques, and assess its efficacy. Method the two-day course consisted of theoretical lectures and practical experience on large-sized swine. Data of the first 126 participants were collected and analyzed. Results All of the 126 general surgeons who had participated in the course judged it to be an efficient model to improve knowledge about the surgical treatment of trauma. Conclusion A two-day course, focusing on trauma surgery, with lectures and life-like operation situations, represents a model for simulated training and can be useful to improve surgeons' confidence in managing trauma patients. Cooperation between organizers of similar initiatives would be beneficial and could lead to standardizing and improving such courses.

  7. The pool of preactivated Lck in the initiation of T-cell signaling: a critical re-evaluation of the Lck standby model

    Czech Academy of Sciences Publication Activity Database

    Ballek, Ondřej; Valečka, Jan; Manning, Jasper; Filipp, Dominik

    2014-01-01

    Roč. 93, spring (2014), s. 384-395. ISSN 0818-9641 R&D Projects: GA ČR GA310/09/2084 Institutional support: RVO:68378050 Keywords : Lck standby model * Lck kinase * TCR triggering * kinetic-segregation model * CD45-deficient T-cell Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.147, year: 2014

  8. The pool of preactivated Lck in the initiation of T-cell signaling: a critical re-evaluation of the Lck standby model

    Czech Academy of Sciences Publication Activity Database

    Ballek, Ondřej; Valečka, Jan; Manning, Jasper; Filipp, Dominik

    2015-01-01

    Roč. 93, č. 4 (2015), s. 384-395. ISSN 0818-9641 R&D Projects: GA ČR GA310/09/2084 Institutional support: RVO:68378050 Keywords : Lck, T-cell * proximal TCR * signaling Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.147, year: 2014

  9. The Western Canada Fuel Cell Initiative (WCFCI)

    International Nuclear Information System (INIS)

    Vision: Western Canada will become an international centre for stationary power generation technology using high temperature fuel cells that use a wide variety of fossil and biomass fuels. Current research areas of investigation: 1. Clean efficient use of hydrocarbons 2. Large-scale electricity generation 3. CO2 sequestration 4. Direct alcohol fuel cells 5. Solid oxide fuel cells. (author)

  10. National Evaluation of the Youth Firearms Violence Initiative.

    Science.gov (United States)

    Dunworth, Terence

    Between 1985 and 1994 the rate of violent criminal acts committed by juveniles rose sharply. Juvenile homicides committed with a handgun more than doubled. This bulletin discusses the national evaluation of the Youth Firearms Violence Initiative (YFVI), a program initiated by the Office of Community Oriented Policing Services (COPS) to fund…

  11. Recommendations for evaluation of health care improvement initiatives.

    Science.gov (United States)

    Parry, Gareth J; Carson-Stevens, Andrew; Luff, Donna F; McPherson, Marianne E; Goldmann, Donald A

    2013-01-01

    Intensive efforts are underway across the world to improve the quality of health care. It is important to use evaluation methods to identify improvement efforts that work well before they are replicated across a broad range of contexts. Evaluation methods need to provide an understanding of why an improvement initiative has or has not worked and how it can be improved in the future. However, improvement initiatives are complex, and evaluation is not always well aligned with the intent and maturity of the intervention, thus limiting the applicability of the results. We describe how initiatives can be grouped into 1 of 3 improvement phases-innovation, testing, and scale-up and spread-depending on the degree of belief in the associated interventions. We describe how many evaluation approaches often lead to a finding of no effect, consistent with what has been termed Rossi's Iron Law of Evaluation. Alternatively, we recommend that the guiding question of evaluation in health care improvement be, "How and in what contexts does a new model work or can be amended to work?" To answer this, we argue for the adoption of formative, theory-driven evaluation. Specifically, evaluations start by identifying a program theory that comprises execution and content theories. These theories should be revised as the initiative develops by applying a rapid-cycle evaluation approach, in which evaluation findings are fed back to the initiative leaders on a regular basis. We describe such evaluation strategies, accounting for the phase of improvement as well as the context and setting in which the improvement concept is being deployed. Finally, we challenge the improvement and evaluation communities to come together to refine the specific methods required so as to avoid the trap of Rossi's Iron Law. PMID:24268081

  12. Initial TMX central-cell ICRH experiments

    International Nuclear Information System (INIS)

    Four topics are discussed in this report: the feasibility of applying ion cyclotron resonance heating (ICRH) in the TMX central cell, some applications of heating, the results of preliminary experiments, and plans for further ICRH experiments

  13. The Role of Ultrasound in Initial Evaluation of Renal Colic

    OpenAIRE

    Abu-Ghazzeh Yaser; Abdu-Alro'f Salah

    2000-01-01

    The objective of this study is to evaluate the use of ultrasound in the initial evaluation of renal colic. We studied prospectively 21 patients referred for radiographic evaluation for renal colic from January 1998 through April 1998. All sonographic studies were performed with real-time sector scanner (Kertz, Compeson 410 using 3.5 MHz Probe). Our sonographic criteria for a positive examination consisted of the visualization of urinary tract calculus and/or unilateral hydronephrosis with or ...

  14. Conjunctival Metastasis as an Initial Sign of Small Cell Lung Cancer

    OpenAIRE

    Afsun Sahin; Nilgun Yildirim; Deniz Goren Sahin; Hikmet Basmak; Mustafa Acikalin

    2014-01-01

    Introduction. To report a case of a conjunctival metastasis as the initial manifestation of small cell lung cancer. Methods. Observational case report. Results. A 50-year-old man without known systemic disease developed a conjunctival mass in his right eye. He underwent incisional biopsy of the tumor and systemic evaluation. Histopathologically, the conjunctival mass was a metastatic small cell carcinoma. Further evaluation revealed a primary small cell lung carcinoma with metastasis to liver...

  15. The role of initial cells in maize anther morphogenesis.

    Science.gov (United States)

    Dawe, R K; Freeling, M

    1992-12-01

    The near absence of cell movement in plants makes clonal analysis a particularly informative method for reconstructing the early events of organ formation. We traced the patterns of cell division during maize anther development by inducing sector boundaries that preceded the earliest events of anther initiation. In doing this, we were able to estimate the smallest number of cells that are fated to form an anther, characteristic cell division patterns that occur during anther morphogenesis, and the relationship between the pre-existing symmetry of the initial cells and the final symmetry of the mature anther. Four general conclusions are made: (1) anthers are initiated from small groups of 12 or fewer cells in each of two floral meristematic layers; (2) the early growth of the anther is more like a shoot than a glume or leaf; (3) cell ancestry does not dictate basic structure and (4) the orientation of initial cells predicts the orientation of the four pollen-containing microsporangia, which define the axes of symmetry on the mature anther. The final point is discussed with other data, and an explanation involving a 'structural template' is invoked. The idea is that the orientation of initial cells within the floral meristem establishes an architectural pattern into which anther cells are recruited without regard to their cellular lineages. The structural template hypothesis may prove to be generally applicable to problems of pattern formation in plants. PMID:1295730

  16. Effects of Recombinant Erythropoietin on Breast Cancer-Initiating Cells

    Directory of Open Access Journals (Sweden)

    Tiffany M. Phillips

    2007-12-01

    Full Text Available BACKGROUND: Cancer anemia causes fatigue and correlates with poor treatment outcome. Erythropoietin has been introduced in an attempt to correct these defects. However, five recent clinical trials reported a negative impact of erythropoietin on survival and/or tumor control, indicating that experimental evaluation of a possible direct effect of erythropoietin on cancer cells is required. Cancer recurrence is thought to rely on the proliferation of cancer initiating cells (CICs. In breast cancer, CICs can be identified by phenotypic markers and their fate is controlled by the Notch pathway. METHODS: In this study, we investigated the effect of erythropoietin on CICs in breast cancer cell lines. Levels of erythropoietin receptor (EpoR, CD24, CD44, Jagged-1 expression, activation of Notch-1 were assessed by flow cytometry. Self-renewing capacity of CICs was investigated in sphere formation assays. RESULTS: EpoR expression was found on the surface of CICs. Recombinant human Epo (rhEpo increased the numbers of CICs and self-renewing capacity in a Notch-dependent fashion by induction of Jagged-1. Inhibitors of the Notch pathway and P13-kinase blocked both effects. CONCLUSIONS: Erythropoietin functionally affects CICs directly. Our observation may explain the negative impact of recombinant Epo on local control and survival of cancer patients with EpoR-positive tumors.

  17. Evaluating School Travel Initiatives and Promoting "Healthy Travel" through PSHCE

    Science.gov (United States)

    Baslington, Hazel

    2010-01-01

    The number of primary school children travelling to school by car in the UK has almost doubled from 22% to 43% in 20 years. A governmental policy response is school travel plans (STPs). This paper reports the findings of an empirical evaluation designed to measure the effectiveness of the travel initiative at three schools. Quantitative and…

  18. Evaluating Business Intelligence Initiatives With Respect To BI Governance

    OpenAIRE

    Muntean, Mihaela; Cornelia MUNTEAN; Cabau, Liviu Gabriel

    2013-01-01

    The BI governance concept is introduced and with respect to the established framework for approaching Business Intelligence strategies, a demarche for evaluating BI initiatives will be proposed. Monte Carlo simulation method will be used to fundament the decision to move forward with a Business Intelligence project.

  19. Evaluating U.S. States climate change initiatives

    International Nuclear Information System (INIS)

    This paper evaluates sub-federal efforts to mitigate climate change in the United States through a range of climate-relevant initiatives, identifying principal trends and detailing climate-relevant initiatives in several states. These strategies include renewable electricity mandates, State and regional greenhouse gas emissions inventories, mandatory greenhouse gas emissions reporting, State greenhouse gas emissions caps, greenhouse gas emissions reductions from motor vehicles, and greenhouse gas emissions cap-and-trade programs for electric generation in several States. Many municipalities in the United States are also pursuing a range of climate-relevant initiatives, those actions are beyond the scope of this paper, but it should be noted they also influence state and national consideration of climate-relevant initiatives in the United States. (author)

  20. A theory-driven evaluation of a wellness initiative

    Directory of Open Access Journals (Sweden)

    Carren Field

    2012-07-01

    Full Text Available Orientation: By reporting on an evaluation of a wellness initiative, this article brings together an element of organisational development (employee wellness with an approach to programme evaluation (programme theory-driven evaluation. Research purpose: Two questions were addressed: ‘What is the causal logic of the wellness initiative?’ and ‘Is this a plausible programme theory according to social science research and literature?’Motivation for the study: A study that could demonstrate the usefulness of the theory-driven evaluation approach, especially in the local human resource (HR domain, was considered to be valuable. In addition, this evaluation provided a careful consideration of how plausible it is for such interventions to achieve what they set out to do.Research design, approach and method: The evaluation relied mainly on qualitative methods (the examination of secondary data and interviewing to extract programme theory, and on literature to assess plausibility.Main findings: The study had two main outcomes: the finalisation of a model of how the programme is supposed to work according to programme staff, and the conclusion that the model is plausible, provided it is implemented at full strength.Practical/managerial implications: Programme staff are advised to pay particular attention to implementation fidelity, especially to employee participation and involvement in the programme’s activities. A number of strategies are recommended to strengthen the effect of the model.Contribution/value-add: This evaluation showed the importance of conducting a theory- driven evaluation, not only in order to understand the programme and its context, but also to provide a basis for an implementation and outcome evaluation.

  1. Evaluating a questionnaire to measure improvement initiatives in Swedish healthcare

    Directory of Open Access Journals (Sweden)

    Andersson Ann-Christine

    2013-02-01

    Full Text Available Abstract Background Quality improvement initiatives have expanded recently within the healthcare sector. Studies have shown that less than 40% of these initiatives are successful, indicating the need for an instrument that can measure the progress and results of quality improvement initiatives and answer questions about how quality initiatives are conducted. The aim of the present study was to develop and test an instrument to measure improvement process and outcome in Swedish healthcare. Methods A questionnaire, founded on the Minnesota Innovation Survey (MIS, was developed in several steps. Items were merged and answer alternatives were revised. Employees participating in a county council improvement program received the web-based questionnaire. Data was analysed by descriptive statistics and correlation analysis. The questionnaire psychometric properties were investigated and an exploratory factor analysis was conducted. Results The Swedish Improvement Measurement Questionnaire consists of 27 items. The Improvement Effectiveness Outcome dimension consists of three items and has a Cronbach’s alpha coefficient of 0.67. The Internal Improvement Processes dimension consists of eight sub-dimensions with a total of 24 items. Cronbach’s alpha coefficient for the complete dimension was 0.72. Three significant item correlations were found. A large involvement in the improvement initiative was shown and the majority of the respondents were satisfied with their work. Conclusions The psychometric property tests suggest initial support for the questionnaire to study and evaluate quality improvement initiatives in Swedish healthcare settings. The overall satisfaction with the quality improvement initiative correlates positively to the awareness of individual responsibilities.

  2. Metastatic Renal Cell Carcinoma Initially Presented as a Tongue Mass

    Directory of Open Access Journals (Sweden)

    Deniz ALTINEL

    2010-09-01

    Full Text Available Renal cell carcinoma is one of the most common tumours after lung and breast cancer to metastasize to the head and neck. Initial presentation by tongue metastasis is extremely rare. A 67-year-oldmale presented with a 4.8 cm mass on his tongue. The result of the punch biopsy from the tongue was diagnosed as a clear cell variant of squamous cell carcinoma. The biopsy was reevaluated due to the renal mass found during the check-up and the rapid enlargement of the mass. The excision of the tongue mass and the radical nephrectomy material confirmed the diagnosis of a metastatic renal cell carcinoma in the tongue and renal cell carcinoma in the kidney. Since metastasis of renal cell carcinoma to the tongue is uncommon it may cause difficulties in diagnosis and proper management. The metastasis of renal cell carcinoma should always be considered in the differential diagnosis among the clear cell neoplasms.

  3. The Role of Ultrasound in Initial Evaluation of Renal Colic

    Directory of Open Access Journals (Sweden)

    Abu-Ghazzeh Yaser

    2000-01-01

    Full Text Available The objective of this study is to evaluate the use of ultrasound in the initial evaluation of renal colic. We studied prospectively 21 patients referred for radiographic evaluation for renal colic from January 1998 through April 1998. All sonographic studies were performed with real-time sector scanner (Kertz, Compeson 410 using 3.5 MHz Probe. Our sonographic criteria for a positive examination consisted of the visualization of urinary tract calculus and/or unilateral hydronephrosis with or without ureterectasis. The presence of urinary calculi was proven in 18 out of 21 patients (85%. The absence of calculi was established in three cases either by negative I.V.U. (2 cases or by the clinical and sonographic demonstration of epididymitis as the cause in one patient. In the 18 patients with proven urinary calculi, ultrasound correctly identified the diagnosis in 15 cases (83%. Of those 15 visualized calculi, 11 were located at the ureterovesicular junction, two in the renal pelvis, one in the proximal third of the ureter, and one in the distal third. The sensitivity of ultasonography to detect renal calculi was 83% and the specificity, 100%. The one false positive examination with unilateral hydronephrosis proved to be due to a retroperitoneal liposarcoma. There were two cases in which the urinary tract ultrasound examination was negative. We conclude that ultrasound has a high diagnostic value when used as the first line investigation for the initial evaluation of renal colic.

  4. Initial evaluation of continuous fiber reinforced NiAl composites

    Science.gov (United States)

    Noebe, R. D.; Bowman, R. R.; Eldridge, J. I.

    1990-01-01

    NiAl is being evaluated as a potential matrix material as part of an overall program to develop and understand high-temperature structural composites. Currently, continuous fiber composites have been fabricated by the powder cloth technique incorporating either W(218) or single crystal Al2O3 fibers as reinforcements in both binary NiAl and a solute strengthened NiAl(.05 at. pct Zr) matrix. Initial evaluation of these composite systems have included: fiber push-out testing to measure matrix/fiber bond strengths, bend testing to determine strength as a function of temperature and composite structure, and thermal cycling to establish the effect of matrix and fiber properties on composite life. The effect of matrix/fiber bond strength and matrix strength on several composite properties will be discussed.

  5. Initial evaluation of continuous fiber reinforced NiAl composites

    International Nuclear Information System (INIS)

    NiAl is being evaluated as a potential matrix material as part of an overall program to develop and understand high-temperature structural composites. Currently, continuous fiber composites have been fabricated by the powder cloth technique incorporating either W(218) or single crystal Al2O3 fibers as reinforcements in both binary NiAl and a solute strengthened NiAl(.05 at. pct Zr) matrix. Initial evaluation of these composite systems have included: fiber push-out testing to measure matrix/fiber bond strengths, bend testing to determine strength as a function of temperature and composite structure, and thermal cycling to establish the effect of matrix and fiber properties on composite life. The effect of matrix/fiber bond strength and matrix strength on several composite properties will be discussed. 18 refs

  6. Computer generation of initial spatial distribution for cell automata

    OpenAIRE

    GuangHua Liu; WenJun Zhang

    2011-01-01

    The algorithm to generate spatial distribution patterns was developed and presented in this study. Three typical spatial distribution patterns, i.e., Poisson distribution, binomial distribution, and negative binomial distribution were included in the algorithm. The Java program was also provided. The algorithm can be used to generate initial distribution in cell automata modeling.

  7. Mitochondria: An intriguing target for killing tumour-initiating cells

    Czech Academy of Sciences Publication Activity Database

    Yan, B.; Dong, L.; Neužil, Jiří

    2016-01-01

    Roč. 26, JAN 2016 (2016), s. 86-93. ISSN 1567-7249 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * ALPHA-TOCOPHERYL SUCCINATE * Therapeutic resistance * Mitochondria Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.249, year: 2014

  8. Future use of mitocans against tumour-initiating cells?

    Czech Academy of Sciences Publication Activity Database

    Morrison, B.J.; Anděra, Ladislav; Reynolds, B.A.; Ralph, S.J.; Neužil, Jiří

    2009-01-01

    Roč. 53, č. 1 (2009), s. 147-153. ISSN 1613-4125 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : mitocans * tumour-initiating cells * metastasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.356, year: 2009

  9. Distributed Initial Synchronization for 5G small cells

    DEFF Research Database (Denmark)

    Berardinelli, Gilberto; Tavares, Fernando Menezes Leitão; Tirkkonen, Olav;

    2014-01-01

    Time synchronization in a large network of small cells enables efficient interference management as well as advanced transmission techniques which can boost the network throughput. In this paper, we focus on the distributed initial synchronization problem and propose different solutions aiming at...

  10. Metastatic Renal Cell Carcinoma Initially Presented as a Tongue Mass

    OpenAIRE

    Altinel, Deniz; Demet ETİT; Tan, Ayça; Ümit BAYOL; Volkan BULUT; Gökçöl Erdoğan, Işın; Beyhan, Rafet; Yusuf YALÇIN

    2010-01-01

    Renal cell carcinoma is one of the most common tumours after lung and breast cancer to metastasize to the head and neck. Initial presentation by tongue metastasis is extremely rare. A 67-year-oldmale presented with a 4.8 cm mass on his tongue. The result of the punch biopsy from the tongue was diagnosed as a clear cell variant of squamous cell carcinoma. The biopsy was reevaluated due to the renal mass found during the check-up and the rapid enlargement of the mass. The excision of the tongue...

  11. Session Initiation Protocol (SIP) Server Overload Control: Design and Evaluation

    CERN Document Server

    Shen, Charles; Nahum, Erich

    2008-01-01

    A Session Initiation Protocol (SIP) server may be overloaded by emergency-induced call volume, ``American Idol'' style flash crowd effects or denial of service attacks. The SIP server overload problem is interesting especially because the costs of serving or rejecting a SIP session can be similar. For this reason, the built-in SIP overload control mechanism based on generating rejection messages cannot prevent the server from entering congestion collapse under heavy load. The SIP overload problem calls for a pushback control solution in which the potentially overloaded receiving server may notify its upstream sending servers to have them send only the amount of load within the receiving server's processing capacity. The pushback framework can be achieved by either a rate-based feedback or a window-based feedback. The centerpiece of the feedback mechanism is the algorithm used to generate load regulation information. We propose three new window-based feedback algorithms and evaluate them together with two exis...

  12. Short telomeres initiate telomere recombination in primary and tumor cells.

    Directory of Open Access Journals (Sweden)

    Tammy A Morrish

    2009-01-01

    Full Text Available Human tumors that lack telomerase maintain telomeres by alternative lengthening mechanisms. Tumors can also form in telomerase-deficient mice; however, the genetic mechanism responsible for tumor growth without telomerase is unknown. In yeast, several different recombination pathways maintain telomeres in the absence of telomerase-some result in telomere maintenance with minimal effects on telomere length. To examine non-telomerase mechanisms for telomere maintenance in mammalian cells, we used primary cells and lymphomas from telomerase-deficient mice (mTR-/- and Emumyc+mTR-/- and CAST/EiJ mouse embryonic fibroblast cells. These cells were analyzed using pq-ratio analysis, telomere length distribution outliers, CO-FISH, Q-FISH, and multicolor FISH to detect subtelomeric recombination. Telomere length was maintained during long-term growth in vivo and in vitro. Long telomeres, characteristic of human ALT cells, were not observed in either late passage or mTR-/- tumor cells; instead, we observed only minimal changes in telomere length. Telomere length variation and subtelomeric recombination were frequent in cells with short telomeres, indicating that length maintenance is due to telomeric recombination. We also detected telomere length changes in primary mTR-/- cells that had short telomeres. Using mouse mTR+/- and human hTERT+/- primary cells with short telomeres, we found frequent length changes indicative of recombination. We conclude that telomere maintenance by non-telomerase mechanisms, including recombination, occurs in primary cells and is initiated by short telomeres, even in the presence of telomerase. Most intriguing, our data indicate that some non-telomerase telomere maintenance mechanisms occur without a significant increase in telomere length.

  13. Mesenchymal stem cells secretomes' affect multiple myeloma translation initiation.

    Science.gov (United States)

    Marcus, H; Attar-Schneider, O; Dabbah, M; Zismanov, V; Tartakover-Matalon, S; Lishner, M; Drucker, L

    2016-06-01

    Bone marrow mesenchymal stem cells' (BM-MSCs) role in multiple myeloma (MM) pathogenesis is recognized. Recently, we have published that co-culture of MM cell lines with BM-MSCs results in mutual modulation of phenotype and proteome (via translation initiation (TI) factors eIF4E/eIF4GI) and that there are differences between normal donor BM-MSCs (ND-MSCs) and MM BM-MSCs (MM-MSCs) in this crosstalk. Here, we aimed to assess the involvement of soluble BM-MSCs' (ND, MM) components, more easily targeted, in manipulation of MM cell lines phenotype and TI with specific focus on microvesicles (MVs) capable of transferring critical biological material. We applied ND and MM-MSCs 72h secretomes to MM cell lines (U266 and ARP-1) for 12-72h and then assayed the cells' (viability, cell count, cell death, proliferation, cell cycle, autophagy) and TI (factors: eIF4E, teIF4GI; regulators: mTOR, MNK1/2, 4EBP; targets: cyclin D1, NFκB, SMAD5, cMyc, HIF1α). Furthermore, we dissected the secretome into >100kDa and autophagy and proliferation. The dissected secretome yielded different effects on MM cell lines phenotype and TI according to fraction (>100kDa- repressed; autophagy and TI whereas MM-MSCs MVs stimulated them. These observations highlight the very complex communication between MM and BM-MSCs and underscore its significance to major processes in the malignant cells. Studies into the influential MVs cargo are underway and expected to uncover targetable signals in the regulation of the TI/proliferation/autophagy cascade. PMID:26976208

  14. Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

    International Nuclear Information System (INIS)

    Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.

  15. Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Li, Qiuping [Zhongshan Hospital of Fudan University, Shanghai 200032 (China); Yang, Zhiyuan; Wu, Guoqiang [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Sun, Shuhui [Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Gu, Jianxin [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Institutes of Biomedical Sciences of Fudan University, Shanghai 200032 (China); Wei, Yuanyan, E-mail: yywei@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Jiang, Jianhai, E-mail: jianhaijiang@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China)

    2010-07-09

    Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.

  16. Ovarian tumor-initiating cells display a flexible metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Angela S. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Roberts, Paul C. [Biomedical Science and Pathobiology, Virginia Tech, Blacksburg, VA (United States); Frisard, Madlyn I. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Hulver, Matthew W., E-mail: hulvermw@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Schmelz, Eva M., E-mail: eschmelz@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States)

    2014-10-15

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

  17. Ovarian tumor-initiating cells display a flexible metabolism

    International Nuclear Information System (INIS)

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-LFFLv (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth

  18. Durability evaluation of reversible solid oxide cells

    Science.gov (United States)

    Zhang, Xiaoyu; O'Brien, James E.; O'Brien, Robert C.; Housley, Gregory K.

    2013-11-01

    An experimental investigation on the performance and durability of single solid oxide cells (SOCs) is under way at the Idaho National Laboratory. Reversible operation of SOCs includes electricity generation in the fuel cell mode and hydrogen generation in the electrolysis mode. Degradation is a more significant issue when operating SOCs in the electrolysis mode. In order to understand and mitigate the degradation issues in high temperature electrolysis, single SOCs with different configurations from several manufacturers have been evaluated for initial performance and long-term durability. Cells were obtained from four industrial partners. Cells from Ceramatec Inc. and Materials and Systems Research Inc. (MSRI) showed improved durability in electrolysis mode compared to previous stack tests. Cells from Saint Gobain Advanced Materials Inc. (St. Gobain) and SOFCPower Inc. demonstrated stable performance in the fuel cell mode, but rapid degradation in the electrolysis mode, especially at high current density. Electrolyte-electrode delamination was found to have a significant impact on degradation in some cases. Enhanced bonding between electrolyte and electrode and modification of the electrode microstructure helped to mitigate degradation. Polarization scans and AC impedance measurements were performed during the tests to characterize cell performance and degradation.

  19. Initial ACTR retrieval technology evaluation test material recommendations

    International Nuclear Information System (INIS)

    Millions of gallons of radiaoctive waste are contained in underground storage tanks at Hanford (SE Washington). Techniques for retrieving much of this waste from the storage tanks have been developed. Current baseline approach is to use sluice jets for single-shell tanks and mixer pumps for double-shell tanks. The Acquire Commercial Technology for Retrieval (ACTR) effort was initiated to identify potential improvements in or alternatives to the baseline waste retrieval methods. Communications with a variety of vendors are underway to identify improved methods that can be implemented at Hanford with little or no additional development. Commercially available retrieval methods will be evaluated by a combination of testing and system-level cost estimation. Current progress toward developing waste simulants for testing ACTR candidate methods is reported; the simulants are designed to model 4 different types of tank waste. Simulant recipes are given for wet sludge, hardpan/dried sludge,hard saltcake, and soft saltcake. Comparisons of the waste and simulant properties are documented in this report

  20. Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

    International Nuclear Information System (INIS)

    There is accumulating evidence that breast cancer may arise from mutated mammary stem/progenitor cells which have been termed breast cancer-initiating cells (BCIC). BCIC identified in clinical specimens based on membrane phenotype (CD44+/CD24−/low and/or CD133+ expression) or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1+), have been demonstrated to have stem/progenitor cell properties, and are tumorigenic when injected in immunocompromized mice at very low concentrations. BCIC have also been isolated and in vitro propagated as non-adherent spheres of undifferentiated cells, and stem cell patterns have been recognized even in cancer cell lines. Recent findings indicate that aberrant regulation of self renewal is central to cancer stem cell biology. Alterations in genes involved in self-renewal pathways, such as Wnt, Notch, sonic hedgehog, PTEN and BMI, proved to play a role in breast cancer progression. Hence, targeting key elements mediating the self renewal of BCIC represents an attractive option, with a solid rationale, clearly identifiable molecular targets, and adequate knowledge of the involved pathways. Possible concerns are related to the poor knowledge of tolerance and efficacy of inhibiting self-renewal mechanisms, because the latter are key pathways for a variety of biological functions and it is unknown whether their interference would kill BCIC or simply temporarily stop them. Thus, efforts to develop BCIC-targeted therapies should not only be focused on interfering on self-renewal, but could seek to identify additional molecular targets, like those involved in regulating EMT-related pathways, in reversing the MDR phenotype, in inducing differentiation and controlling cell survival pathways

  1. Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

    Directory of Open Access Journals (Sweden)

    Maria Grazia Daidone

    2011-03-01

    Full Text Available There is accumulating evidence that breast cancer may arise from mutated mammary stem/progenitor cells which have been termed breast cancer-initiating cells (BCIC. BCIC identified in clinical specimens based on membrane phenotype (CD44+/CD24−/low and/or CD133+ expression or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1+, have been demonstrated to have stem/progenitor cell properties, and are tumorigenic when injected in immunocompromized mice at very low concentrations. BCIC have also been isolated and in vitro propagated as non-adherent spheres of undifferentiated cells, and stem cell patterns have been recognized even in cancer cell lines. Recent findings indicate that aberrant regulation of self renewal is central to cancer stem cell biology. Alterations in genes involved in self-renewal pathways, such as Wnt, Notch, sonic hedgehog, PTEN and BMI, proved to play a role in breast cancer progression. Hence, targeting key elements mediating the self renewal of BCIC represents an attractive option, with a solid rationale, clearly identifiable molecular targets, and adequate knowledge of the involved pathways. Possible concerns are related to the poor knowledge of tolerance and efficacy of inhibiting self-renewal mechanisms, because the latter are key pathways for a variety of biological functions and it is unknown whether their interference would kill BCIC or simply temporarily stop them. Thus, efforts to develop BCIC-targeted therapies should not only be focused on interfering on self-renewal, but could seek to identify additional molecular targets, like those involved in regulating EMT-related pathways, in reversing the MDR phenotype, in inducing differentiation and controlling cell survival pathways.

  2. Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Santilli, Guido; Binda, Mara; Zaffaroni, Nadia; Daidone, Maria Grazia, E-mail: mariagrazia.daidone@istitutotumori.mi.it [Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS-Istituto Nazionale dei Tumori, Via Amadeo 42, Milan 20133 (Italy)

    2011-03-16

    There is accumulating evidence that breast cancer may arise from mutated mammary stem/progenitor cells which have been termed breast cancer-initiating cells (BCIC). BCIC identified in clinical specimens based on membrane phenotype (CD44{sup +}/CD24{sup −/low} and/or CD133{sup +} expression) or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1{sup +}), have been demonstrated to have stem/progenitor cell properties, and are tumorigenic when injected in immunocompromized mice at very low concentrations. BCIC have also been isolated and in vitro propagated as non-adherent spheres of undifferentiated cells, and stem cell patterns have been recognized even in cancer cell lines. Recent findings indicate that aberrant regulation of self renewal is central to cancer stem cell biology. Alterations in genes involved in self-renewal pathways, such as Wnt, Notch, sonic hedgehog, PTEN and BMI, proved to play a role in breast cancer progression. Hence, targeting key elements mediating the self renewal of BCIC represents an attractive option, with a solid rationale, clearly identifiable molecular targets, and adequate knowledge of the involved pathways. Possible concerns are related to the poor knowledge of tolerance and efficacy of inhibiting self-renewal mechanisms, because the latter are key pathways for a variety of biological functions and it is unknown whether their interference would kill BCIC or simply temporarily stop them. Thus, efforts to develop BCIC-targeted therapies should not only be focused on interfering on self-renewal, but could seek to identify additional molecular targets, like those involved in regulating EMT-related pathways, in reversing the MDR phenotype, in inducing differentiation and controlling cell survival pathways.

  3. Experimental evaluation of cell liners

    International Nuclear Information System (INIS)

    Cell liners may be used in breeder reactor sodium pipe ways, sodium cells, and lower cavity region to provide a leak-tight cell and to protect the concrete from sodium in the unlikely event of a sodium spill. The objectives of the HEDL liner verification test program are to evaluate the integrity of liner concepts under postulated accident conditions and to develop the experimental data base which will demonstrate that liners will not fail. Two specific tests are reported; a high temperature liner feature test, and a large-scale liner sodium spill test. In both tests no failures of the liners or tendencies toward failure were detected. The discussed liner designs appeared to be conservative, and the liner strength appeared to be more than adequate

  4. Positive correlation between size at initiation of chromosome replication in Escherichia coli and size at initiation of cell constriction.

    OpenAIRE

    Koppes, L J; Nanninga, N.

    1980-01-01

    The variability of (i) the length (size) at which cells initiate chromosome replication, (ii) the length at which they initiate cell constriction, and (iii) the time interval between these events has been estimated for Escherichia coli B/r K at two different slow growth rates. Steady-state cultures were pulse-labeled with [3H]thymidine and, after fixation, analyzed by electron microscopic radioautography. The coefficient of variation of length at initiation of chromosome replication was found...

  5. 38 CFR 21.376 - Travel expenses for initial evaluation and counseling.

    Science.gov (United States)

    2010-07-01

    ... initial evaluation and counseling. 21.376 Section 21.376 Pensions, Bonuses, and Veterans' Relief... Travel expenses for initial evaluation and counseling. When VA asks a disabled veteran to report to a designated place for an initial evaluation, reevaluation or counseling (including personal or...

  6. Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance

    International Nuclear Information System (INIS)

    Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 103 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 105 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, Si

  7. Long-lived intestinal tuft cells serve as colon cancer–initiating cells

    Science.gov (United States)

    Westphalen, C. Benedikt; Asfaha, Samuel; Hayakawa, Yoku; Takemoto, Yoshihiro; Lukin, Dana J.; Nuber, Andreas H.; Brandtner, Anna; Setlik, Wanda; Remotti, Helen; Muley, Ashlesha; Chen, Xiaowei; May, Randal; Houchen, Courtney W.; Fox, James G.; Gershon, Michael D.; Quante, Michael; Wang, Timothy C.

    2014-01-01

    Doublecortin-like kinase 1 protein (DCLK1) is a gastrointestinal tuft cell marker that has been proposed to identify quiescent and tumor growth–sustaining stem cells. DCLK1+ tuft cells are increased in inflammation-induced carcinogenesis; however, the role of these cells within the gastrointestinal epithelium and their potential as cancer-initiating cells are poorly understood. Here, using a BAC-CreERT–dependent genetic lineage–tracing strategy, we determined that a subpopulation of DCLK1+ cells is extremely long lived and possesses rare stem cell abilities. Moreover, genetic ablation of Dclk1 revealed that DCLK1+ tuft cells contribute to recovery following intestinal and colonic injury. Surprisingly, conditional knockdown of the Wnt regulator APC in DCLK1+ cells was not sufficient to drive colonic carcinogenesis under normal conditions; however, dextran sodium sulfate–induced (DSS-induced) colitis promoted the development of poorly differentiated colonic adenocarcinoma in mice lacking APC in DCLK1+ cells. Importantly, colonic tumor formation occurred even when colitis onset was delayed for up to 3 months after induced APC loss in DCLK1+ cells. Thus, our data define an intestinal DCLK1+ tuft cell population that is long lived, quiescent, and important for intestinal homeostasis and regeneration. Long-lived DCLK1+ cells maintain quiescence even following oncogenic mutation, but are activated by tissue injury and can serve to initiate colon cancer. PMID:24487592

  8. Tumor-Initiating and -Propagating Cells: Cells That We Would to Identify and Control

    OpenAIRE

    Berit Bølge Tysnes

    2010-01-01

    Identification of the cell types capable of initiating and sustaining growth of the neoplastic clone in vivo is a fundamental problem in cancer research. It is likely that tumor growth can be sustained both by rare cancer stem-like cells and selected aggressive clones and that the nature of the mutations, the cell of origin, and its environment will contribute to tumor propagation. Genomic instability, suggested as a driving force in tumorigenesis, may be induced by genetic and epigenetic cha...

  9. Tumor-Initiating and -Propagating Cells: Cells That We Would Like to Identify and Control1

    OpenAIRE

    Tysnes, Berit Bølge

    2010-01-01

    Identification of the cell types capable of initiating and sustaining growth of the neoplastic clone in vivo is a fundamental problem in cancer research. It is likely that tumor growth can be sustained both by rare cancer stem-like cells and selected aggressive clones and that the nature of the mutations, the cell of origin, and its environment will contribute to tumor propagation. Genomic instability, suggested as a driving force in tumorigenesis, may be induced by genetic and epigenetic cha...

  10. Apoptosis and cell-cycle arrest in human and murine tumor cells are initiated by isoprenoids.

    Science.gov (United States)

    Mo, H; Elson, C E

    1999-04-01

    Diverse classes of phytochemicals initiate biological responses that effectively lower cancer risk. One class of phytochemicals, broadly defined as pure and mixed isoprenoids, encompasses an estimated 22,000 individual components. A representative mixed isoprenoid, gamma-tocotrienol, suppresses the growth of murine B16(F10) melanoma cells, and with greater potency, the growth of human breast adenocarcinoma (MCF-7) and human leukemic (HL-60) cells. beta-Ionone, a pure isoprenoid, suppresses the growth of B16 cells and with greater potency, the growth of MCF-7, HL-60 and human colon adenocarcinoma (Caco-2) cells. Results obtained with diverse cell lines differing in ras and p53 status showed that the isoprenoid-mediated suppression of growth is independent of mutated ras and p53 functions. beta-Ionone suppressed the growth of human colon fibroblasts (CCD-18Co) but only when present at three-fold the concentration required to suppress the growth of Caco-2 cells. The isoprenoids initiated apoptosis and, concomitantly arrested cells in the G1 phase of the cell cycle. Both suppress 3-hydroxy-3-methylglutaryl CoA reductase activity. beta-Ionone and lovastatin interfered with the posttranslational processing of lamin B, an activity essential to assembly of daughter nuclei. This interference, we postulate, renders neosynthesized DNA available to the endonuclease activities leading to apoptotic cell death. Lovastatin-imposed mevalonate starvation suppressed the glycosylation and translocation of growth factor receptors to the cell surface. As a consequence, cells were arrested in the G1 phase of the cell cycle. This rationale may apply to the isoprenoid-mediated G1-phase arrest of tumor cells. The additive and potentially synergistic actions of these isoprenoids in the suppression of tumor cell proliferation and initiation of apoptosis coupled with the mass action of the diverse isoprenoid constituents of plant products may explain, in part, the impact of fruit, vegetable

  11. Lidamycin inhibits tumor initiating cells of hepatocellular carcinoma Huh7 through GSK3β/β-catenin pathway.

    Science.gov (United States)

    Chen, Yi; Yu, Dongke; Zhang, Caixia; Shang, Boyang; He, Hongwei; Chen, Jinjing; Zhang, Hao; Zhao, Wuli; Wang, Zhen; Xu, Xiaoyu; Zhen, Yongsu; Shao, Rong-guang

    2015-01-01

    Recently, tumor initiating cells are considered as the central role of tumorigenicity in hepatocellular carcinoma. Enediyne anticancer antibiotic lidamycin with great potential antitumor activity is currently evaluated in Phase II clinical trials. In this study, we evaluated the effect of lidamycin on tumor initiating cells of hepatocellular carcinoma Huh7 and identified the potential mechanism. Flow cytometry analysis and sorting assay, surface marker assay, sphere formation assay, and aldefluor assay were used to evaluate the effect of lidamycin on Huh7 tumor initiating cells in vitro. To investigate the potential mechanism, the activity of GSK3β/β-catenin pathway was detected by Western blot and T cell factors transcriptional activity assay. Subcutaneous tumor model in nude mice was used to observe in vivo effect of lidamycin on Huh7 cells. Lidamycin decreased the proportion of EpCAM+ cells and the expression of EpCAM protein. Lidamycin inhibited sphere formation of sorted EpCAM+ cells in 7 d, and of parental cells in three serial passages. The population of aldehyde dehydrogenase-positive cells was reduced by lidamycin. In addition, lidamycin restrained tumor volume and incidence in vivo. Lidamycin activated GSK3β, and degraded the activity of β-catenin. Consequently, transcriptional activity of β-catenin/T cell factors was decreased. In brief, these results suggest that lidamycin suppressed Huh7 tumor initiating cells via GSK3β/β-catenin pathway. These findings reveal the potential mechanism of lidamycin on tumor initiating cells and the benefit for further clinical evaluation. PMID:23857500

  12. The Evaluation of Large Research Initiatives: A Participatory Integrative Mixed-Methods Approach

    Science.gov (United States)

    Trochim, William M.; Marcus, Stephen E.; Masse, Louise C.; Moser, Richard P.; Weld, Patrick C.

    2008-01-01

    Over the past few decades there has been a rise in the number of federally funded large scientific research initiatives, with increased calls to evaluate their processes and outcomes. This article describes efforts to evaluate such initiatives in one agency within the U.S. federal government. The authors introduce the Evaluation of Large…

  13. Identification of tumor-initiating cells in a canine hepatocellular carcinoma cell line.

    Science.gov (United States)

    Michishita, Masaki; Ezaki, Shiori; Ogihara, Kikumi; Naya, Yuko; Azakami, Daigo; Nakagawa, Takayuki; Sasaki, Nobuo; Arai, Toshiro; Shida, Takuo; Takahashi, Kimimasa

    2014-04-01

    Tumor-initiating cells (TICs) or cancer stem cells (CSCs), a small subset of tumor cells, are involved in tumor initiation, progression, recurrence and metastasis. In human hepatocellular carcinoma (HCC), TICs are enriched with cell surface markers and have the ability to self-renew and differentiate tumors at a high frequency. We established a canine HCC cell line, HCC930599, and analyzed it for stem and progenitor cell marker expression using flow cytometry. HCC930599 showed high CD44 and CD29, moderate CD90, and low CD133, CD34, CD24, CD117, and CD13 expression. CD90(+)CD44(+) and CD90(-)CD44(+) cells were characterized using the in vitro sphere assay and an in vivo transplant model. CD90(+)CD44(+) cells acquired enhanced self-renewal capacity, proliferative activity and tumourigenicity compared with CD90(-)CD44(+) cells, suggesting that TICs exist in the HCC930599 cell line and that CD90 is a marker for enriched TICs. Understanding TIC characteristics may help elucidate hepatic carcinogenesis and HCC therapy development. PMID:24534130

  14. Initial activation of EpCAM cleavage via cell-to-cell contact

    International Nuclear Information System (INIS)

    Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein, which is frequently over-expressed in simple epithelia, progenitors, embryonic and tissue stem cells, carcinoma and cancer-initiating cells. Besides functioning as a homophilic adhesion protein, EpCAM is an oncogenic receptor that requires regulated intramembrane proteolysis for activation of its signal transduction capacity. Upon cleavage, the extracellular domain EpEX is released as a soluble ligand while the intracellular domain EpICD translocates into the cytoplasm and eventually into the nucleus in combination with four-and-a-half LIM domains protein 2 (FHL2) and β-catenin, and drives cell proliferation. EpCAM cleavage, induction of the target genes, and transmission of proliferation signals were investigated under varying density conditions using confocal laser scanning microscopy, immunoblotting, cell counting, and conditional cell systems. EpCAM cleavage, induction of the target genes, and transmission of proliferation signals were dependent on adequate cell-to-cell contact. If cell-to-cell contact was prohibited EpCAM did not provide growth advantages. If cells were allowed to undergo contact to each other, EpCAM transmitted proliferation signals based on signal transduction-related cleavage processes. Accordingly, the pre-cleaved version EpICD was not dependent on cell-to-cell contact in order to induce c-myc and cell proliferation, but necessitated nuclear translocation. For the case of contact-inhibited cells, although cleavage of EpCAM occurred, nuclear translocation of EpICD was reduced, as were EpCAM effects. Activation of EpCAM's cleavage and oncogenic capacity is dependent on cellular interaction (juxtacrine) to provide for initial signals of regulated intramembrane proteolysis, which then support signalling via soluble EpEX (paracrine)

  15. Tumour-initiating cells vs. cancer 'stem' cells and CD133: What's in the name?

    International Nuclear Information System (INIS)

    Recent evidence suggests that a subset of cells within a tumour have 'stem-like' characteristics. These tumour-initiating cells, distinct from non-malignant stem cells, show low proliferative rates, high self-renewing capacity, propensity to differentiate into actively proliferating tumour cells, resistance to chemotherapy or radiation, and they are often characterised by elevated expression of the stem cell surface marker CD133. Understanding the molecular biology of the CD133+ cancer cells is now essential for developing more effective cancer treatments. These may include drugs targeting organelles, such as mitochondria or lysosomes, using highly efficient and selective inducers of apoptosis. Alternatively, agents or treatment regimens that enhance sensitivity of these therapy-resistant 'tumour stem cells' to the current or emerging anti-tumour drugs would be of interest as well

  16. Initial evaluation of a continuous speech recognition program for radiology

    OpenAIRE

    Kanal, KM; Hangiandreou, NJ; Sykes, AM; Eklund, HE; Araoz, PA; Leon, JA; Erickson, BJ

    2001-01-01

    The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers, and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging ex...

  17. Session Initiation Protocol (SIP) Server Overload Control: Design and Evaluation

    OpenAIRE

    Shen, Charles; Schulzrinne, Henning; Nahum, Erich

    2008-01-01

    A Session Initiation Protocol (SIP) server may be overloaded by emergency-induced call volume, ``American Idol'' style flash crowd effects or denial of service attacks. The SIP server overload problem is interesting especially because the costs of serving or rejecting a SIP session can be similar. For this reason, the built-in SIP overload control mechanism based on generating rejection messages cannot prevent the server from entering congestion collapse under heavy load. The SIP overload pro...

  18. Long-lived intestinal tuft cells serve as colon cancer-initiating cells.

    Science.gov (United States)

    Westphalen, C Benedikt; Asfaha, Samuel; Hayakawa, Yoku; Takemoto, Yoshihiro; Lukin, Dana J; Nuber, Andreas H; Brandtner, Anna; Setlik, Wanda; Remotti, Helen; Muley, Ashlesha; Chen, Xiaowei; May, Randal; Houchen, Courtney W; Fox, James G; Gershon, Michael D; Quante, Michael; Wang, Timothy C

    2014-03-01

    Doublecortin-like kinase 1 protein (DCLK1) is a gastrointestinal tuft cell marker that has been proposed to identify quiescent and tumor growth-sustaining stem cells. DCLK1⁺ tuft cells are increased in inflammation-induced carcinogenesis; however, the role of these cells within the gastrointestinal epithelium and their potential as cancer-initiating cells are poorly understood. Here, using a BAC-CreERT-dependent genetic lineage-tracing strategy, we determined that a subpopulation of DCLK1⁺ cells is extremely long lived and possesses rare stem cell abilities. Moreover, genetic ablation of Dclk1 revealed that DCLK1⁺ tuft cells contribute to recovery following intestinal and colonic injury. Surprisingly, conditional knockdown of the Wnt regulator APC in DCLK1⁺ cells was not sufficient to drive colonic carcinogenesis under normal conditions; however, dextran sodium sulfate-induced (DSS-induced) colitis promoted the development of poorly differentiated colonic adenocarcinoma in mice lacking APC in DCLK1⁺ cells. Importantly, colonic tumor formation occurred even when colitis onset was delayed for up to 3 months after induced APC loss in DCLK1⁺ cells. Thus, our data define an intestinal DCLK1⁺ tuft cell population that is long lived, quiescent, and important for intestinal homeostasis and regeneration. Long-lived DCLK1⁺ cells maintain quiescence even following oncogenic mutation, but are activated by tissue injury and can serve to initiate colon cancer. PMID:24487592

  19. Treatment of initially metastatic small-cell lung cancer

    International Nuclear Information System (INIS)

    Lung cancer (LC) is the most common cause of death associated with neoplasms. The incidence of LC in 2007 was 71.3/100,000 men and 18.6/100,000 women in Slovakia. Small-cell lung cancer (SCLC) includes 15 - 18% of all cases. The diagnosis of LC is based on patient's history, physical examination, basic laboratory tests, x-ray imaging and computed tomography (CT) imaging and histology. The material required for histology can be obtained by means of endoscopy or surgery. Ultrasonography (USG) and/or CT of abdomen is commonly performed as a part of staging process, along with CT or MRI of brain. Bone scan is performed in case of suspicion of bone involvement. According to TNM classification, seventh edition, the same classification can be used for SCLC and non-small cell lung cancer (NSCLC). Chemotherapy and radiotherapy are available for treatment of initially metastatic SCLC. First-line chemotherapy regimen should be based on combination of cisplatin or carboplatin with etoposide (PE). Alternatively, CAV regimen (cyclophosphamide, doxorubicin, vincristine) can be used. Newer regimens did not provide benefit when compared to standard regimens. If progression occurs later than 3 months after finishing first-line chemotherapy, the same regimen may be used in second-line chemotherapy. If progression occurs earlier than 3 months after finishing first-line chemotherapy, topotecan-based regimen is an option for second-line line chemotherapy. Despite promising outcomes of amrubicin-based second-line chemotherapy in Japan, amrubicin is not available in countries of E U. Standard therapy schedules do not include radiotherapy targeted on primary tumor and affected lymph-nodes. According to American and European guidelines, prophylactic cranial irradiation is recommended for patients with extensive disease-SCLC with good performance status after achieving complete or partial response to first-line chemotherapy. (author)

  20. Endothelial cell-initiated extravasation of cancer cells visualized in zebrafish

    Directory of Open Access Journals (Sweden)

    Masamitsu Kanada

    2014-12-01

    Full Text Available The extravasation of cancer cells, a key step for distant metastasis, is thought to be initiated by disruption of the endothelial barrier by malignant cancer cells. An endothelial covering-type extravasation of cancer cells in addition to conventional cancer cell invasion-type extravasation was dynamically visualized in a zebrafish hematogenous metastasis model. The inhibition of VEGF-signaling impaired the invasion-type extravasation via inhibition of cancer cell polarization and motility. Paradoxically, the anti-angiogenic treatment showed the promotion, rather than the inhibition, of the endothelial covering-type extravasation of cancer cells, with structural changes in the endothelial walls. These findings may be a set of clues to the full understanding of the metastatic process as well as the metastatic acceleration by anti-angiogenic reagents observed in preclinical studies.

  1. Tumour-initiating cells vs. cancer "stem" cells and CD133: What's in the name?

    Czech Academy of Sciences Publication Activity Database

    Neužil, Jiří; Stantic, M.; Zobalová, Renata; Chladová, Jaromíra; Wang, X. F.; Procházka, L.; Dong, L.; Anděra, Ladislav; Ralph, S.J.

    2007-01-01

    Roč. 255, č. 4 (2007), s. 855-859. ISSN 0006-291X Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : tumour-initiating cells * CD133 * resistance to treatment Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.749, year: 2007

  2. Mission essential service: evaluation and enrichment of afloat MWR initiatives

    OpenAIRE

    David A. Kennett

    1996-01-01

    This thesis evaluates the effectiveness of medium-sized surface combatants with respect to managed MWR programming and positive organizational outcomes that relate to mission readiness. These social and professional outcomes include morale, cohesion, job satisfaction, organizational commitment, work stress reduction, wellness, good order and discipline, and productivity. Substantial evidence exists that well-managed afloat MWR and comparable private sector programs have a significant impact o...

  3. Electricity in Zanzibar's Unguja Island: Initial Evaluation Findings

    OpenAIRE

    Denzel Hankinson; Lauren Pierce; Duncan Chaplin; Arif Mamun; Minki Chatterji; Shawn Powers; Elana Safran

    2011-01-01

    This issue brief presents baseline findings from the impact evaluation and the case study before the installation of a new electricity cable connecting Unguja Island in Zanzibar to the electricity grid of mainland Tanzania. Information for the baseline analysis comes from electricity data provided by the Millennium Challenge Account-Tanzania and the Zanzibar Electricity Company. The case study is based on a survey of 30 hotels. A follow-up analysis will take place in 2013.

  4. The Effect of Initial Cell Concentration on Xylose Fermentation by Pichia stipitis

    Science.gov (United States)

    Agbogbo, Frank K.; Coward-Kelly, Guillermo; Torry-Smith, Mads; Wenger, Kevin; Jeffries, Thomas W.

    Xylose was fermented using Pichia stipitis CBS 6054 at different initial cell concentrations. A high initial cell concentration increased the rate of xylose utilization, ethanol formation, and the ethanol yield. The highest ethanol concentration of 41.0 g/L and a yield of 0.38 g/g was obtained using an initial cell concentration of 6.5 g/L. Even though more xylitol was produced when the initial cell concentrations were high, cell density had no effect on the final ethanol yield. A two-parameter mathematical model was used to predict the cell population dynamics at the different initial cell concentrations. The model parameters, a and b correlate with the initial cell concentrations used with an R 2 of 0.99.

  5. Predictors of Late HIV Diagnosis among Adult People Living with HIV/AIDS Who Undertake an Initial CD4 T Cell Evaluation, Northern Ethiopia: A Case-Control Study

    OpenAIRE

    Beyene, Melkamu Bedimo; Beyene, Habtamu Bedimo

    2015-01-01

    Introduction Early HIV testing and timely initiation of ART is critical for the improved quality of life of PLWHIV. Having identified a higher rates of Late HIV diagnosis, this study was aimed to determine Determinants of late diagnosis of HIV among adult HIV patients in Bahir Dar, Northern Ethiopia. Methods A case control study was conducted between January 2010 to December 2011 at Bahir Dar Felege Hiwot Referral Hospital. The study subjects consisted of 267 cases and 267 controls. Cases wer...

  6. Primitive human hematopoietic cells give rise to differentially specified daughter cells upon their initial cell division.

    NARCIS (Netherlands)

    Giebel, B.; Zhang, T.; Beckmann, J.; Spanholtz, J.; Wernet, P.; Ho, A.; Punzel, M.

    2006-01-01

    It is often predicted that stem cells divide asymmetrically, creating a daughter cell that maintains the stem-cell capacity, and 1 daughter cell committed to differentiation. While asymmetric stem-cell divisions have been proven to occur in model organisms (eg, in Drosophila), it remains illusive wh

  7. Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

    Directory of Open Access Journals (Sweden)

    Nicolas Goffart

    2013-08-01

    Full Text Available Glioblastoma multiforme (GBM, WHO grade IV is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.

  8. Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

    Energy Technology Data Exchange (ETDEWEB)

    Goffart, Nicolas [Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liège, Liège 4000 (Belgium); Kroonen, Jérôme [Human Genetics, CHU and University of Liège, Liège 4000 (Belgium); The T& P Bohnenn Laboratory for Neuro-Oncology, Department of Neurology and Neurosurgery, UMC Utrecht, Utrecht 3556 (Netherlands); Rogister, Bernard, E-mail: Bernard.Register@ulg.ac.be [Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liège, Liège 4000 (Belgium); Department of Neurology, CHU and University of Liège, Liège 4000 (Belgium); GIGA-Development, Stem Cells and Regenerative Medicine, University of Liège, Liège 4000 (Belgium)

    2013-08-14

    Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.

  9. Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

    International Nuclear Information System (INIS)

    Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology

  10. Initial evaluation of a full breast digital system

    International Nuclear Information System (INIS)

    Full-field digital mammography systems have been developed for overcoming the limitations of the screen-film mammography. This work is focused on the system from GE Medical Systems (Senographe 2000) which has been recently installed in our institution. The imager consists of a thin Ics:Tl scintillator which is in narrow contact with an array of amorphous silicon detectors mounted in a single panel. The flat-panel detector is integrated in a x-ray system with a high-frequency generator Senographe DM and dual track anode of Mo and Rh with Mo and Rh filtration. The aim of this work is to analyse the defaults exposure factors set at the installation of the x-ray unit. The image quality has been evaluated by using one of the two phantoms recommended in the ACR Accreditation Program. Phantom images were obtained at each of the three available imaging modes: contrast (CNT), standard (STD) and DOSE. While maintaining the defaults of kilovoltage and anode/filter combination, phantom images were obtained at lower dose vales. The contrast noise ratio (CNR) was calculated for each of the low contrast objects (masses) of the phantom images and the detail visibility was also evaluated. The results obtained for both parameters reveal that similar image quality can be obtained with significant reductions of the average glandular dose. (author)

  11. Initial clinical evaluation of stationary digital chest tomosynthesis

    Science.gov (United States)

    Hartman, Allison E.; Shan, Jing; Wu, Gongting; Lee, Yueh Z.; Zhou, Otto; Lu, Jianping; Heath, Michael; Wang, Xiaohui; Foos, David

    2016-03-01

    Computed Tomography (CT) is the gold standard for image evaluation of lung disease, including lung cancer and cystic fibrosis. It provides detailed information of the lung anatomy and lesions, but at a relatively high cost and high dose of radiation. Chest radiography is a low dose imaging modality but it has low sensitivity. Digital chest tomosynthesis (DCT) is an imaging modality that produces 3D images by collecting x-ray projection images over a limited angle. DCT is less expensive than CT and requires about 1/10th the dose of radiation. Commercial DCT systems acquire the projection images by mechanically scanning an x-ray tube. The movement of the tube head limits acquisition speed. We recently demonstrated the feasibility of stationary digital chest tomosynthesis (s-DCT) using a carbon nanotube (CNT) x-ray source array in benchtop phantom studies. The stationary x-ray source allows for fast image acquisition. The objective of this study is to demonstrate the feasibility of s-DCT for patient imaging. We have successfully imaged 31 patients. Preliminary evaluation by board certified radiologists suggests good depiction of thoracic anatomy and pathology.

  12. Mexico City Air Quality Research Initiative; Volume 5, Strategic evaluation

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-03-01

    Members of the Task HI (Strategic Evaluation) team were responsible for the development of a methodology to evaluate policies designed to alleviate air pollution in Mexico City. This methodology utilizes information from various reports that examined ways to reduce pollutant emissions, results from models that calculate the improvement in air quality due to a reduction in pollutant emissions, and the opinions of experts as to the requirements and trade-offs that are involved in developing a program to address the air pollution problem in Mexico City. The methodology combines these data to produce comparisons between different approaches to improving Mexico City`s air quality. These comparisons take into account not only objective factors such as the air quality improvement or cost of the different approaches, but also subjective factors such as public acceptance or political attractiveness of the different approaches. The end result of the process is a ranking of the different approaches and, more importantly, the process provides insights into the implications of implementing a particular approach or policy.

  13. Initial evaluation of discrete orthogonal basis reconstruction of ECT images

    International Nuclear Information System (INIS)

    Discrete orthogonal basis restoration (DOBR) is a linear, non-iterative, and robust method for solving inverse problems for systems characterized by shift-variant transfer functions. This simulation study evaluates the feasibility of using DOBR for reconstructing emission computed tomographic (ECT) images. The imaging system model uses typical SPECT parameters and incorporates the effects of attenuation, spatially-variant PSF, and Poisson noise in the projection process. Sample reconstructions and statistical error analyses for a class of digital phantoms compare the DOBR performance for Hartley and Walsh basis functions. Test results confirm that DOBR with either basis set produces images with good statistical properties. No problems were encountered with reconstruction instability. The flexibility of the DOBR method and its consistent performance warrants further investigation of DOBR as a means of ECT image reconstruction

  14. A Systematic Analysis of Cell Cycle Regulators in Yeast Reveals That Most Factors Act Independently of Cell Size to Control Initiation of Division

    OpenAIRE

    Scott A Hoose; Jeremy A Rawlings; Kelly, Michelle M.; M Camille Leitch; Ababneh, Qotaiba O; Robles, Juan P.; David Taylor; Hoover, Evelyn M.; Bethel Hailu; McEnery, Kayla A.; S Sabina Downing; Deepika Kaushal; Yi Chen; Alex Rife; Kirtan A Brahmbhatt

    2012-01-01

    Upstream events that trigger initiation of cell division, at a point called START in yeast, determine the overall rates of cell proliferation. The identity and complete sequence of those events remain unknown. Previous studies relied mainly on cell size changes to identify systematically genes required for the timely completion of START. Here, we evaluated panels of non-essential single gene deletion strains for altered DNA content by flow cytometry. This analysis revealed that most gene dele...

  15. Chemo-radionuclide therapy for thyroid cancer. Initial experimental study with cultured cells

    Energy Technology Data Exchange (ETDEWEB)

    Misaki, Takashi; Iwata, Masahiro; Iida, Yasuhiro; Kasagi, Kanji; Konishi, Junji [Kyoto Univ. (Japan). Graduate School of Medicine

    2002-09-01

    Radioiodine therapy has long been used for distant metastases of thyroid cancer. Although partially effective in most cases, it can render a complete cure only in a limited number of patients. One way to enhance its efficacy would be to combine it with antineoplastic agents. Here we describe an initial in vitro evaluation with 4 thyroid cancer cell lines. Cells were sparsely seeded in microtiter plates and allowed to grow for 2 days; then they were exposed to sublethal concentrations of cisplatin (CDDP), doxorubicin (Dox), or 5-fluorouracil (5-FU), followed by treatment with I-131 for 48 hr. Cell survival was measured with a commercial kit based on the colorimetry of succinate dehydrogenase activity. Chemotherapeutic drugs exerted similar concentration-dependent cytotoxic effects in all 4 cell lines. The doses necessary to reduce the surviving fraction to half of the control were about 3 {mu}g/ml for CDDP, 0.3 {mu}g/ml for Dox, and 3 {mu}g/ml for 5-FU (when used continuously for 48 hours). On the other hand, sensitivity to I-131 irradiation differed among the lines; same doses (7.4-14.8 MBq/ml) caused the greatest damage in FRO cells, a modest effect in NPA and WRO, and only minimal change in B-CPAP. The combined effect was most demonstrable in wells treated with Dox and radioiodine, whereas the addition of CDDP or 5-FU had marginal or insignificant merit, respectively. In FRO cells, half-lethal doses of the above mentioned CDDP, Dox, and 5-FU, when used together with 14.8 MBq/ml I-131, reduced cell survival to 54.5%, 29.4% and 33.4%, respectively, vs. 60.2% with radioiodine alone. In vitro, clinical concentrations of Dox can accelerate the killing of thyroid cancer cells by radioiodine. These favorable experimental results warrant future studies to evaluate whether this new bidisciplinary approach is clinically relevant and feasible. (author)

  16. Chemo-radionuclide therapy for thyroid cancer. Initial experimental study with cultured cells

    International Nuclear Information System (INIS)

    Radioiodine therapy has long been used for distant metastases of thyroid cancer. Although partially effective in most cases, it can render a complete cure only in a limited number of patients. One way to enhance its efficacy would be to combine it with antineoplastic agents. Here we describe an initial in vitro evaluation with 4 thyroid cancer cell lines. Cells were sparsely seeded in microtiter plates and allowed to grow for 2 days; then they were exposed to sublethal concentrations of cisplatin (CDDP), doxorubicin (Dox), or 5-fluorouracil (5-FU), followed by treatment with I-131 for 48 hr. Cell survival was measured with a commercial kit based on the colorimetry of succinate dehydrogenase activity. Chemotherapeutic drugs exerted similar concentration-dependent cytotoxic effects in all 4 cell lines. The doses necessary to reduce the surviving fraction to half of the control were about 3 μg/ml for CDDP, 0.3 μg/ml for Dox, and 3 μg/ml for 5-FU (when used continuously for 48 hours). On the other hand, sensitivity to I-131 irradiation differed among the lines; same doses (7.4-14.8 MBq/ml) caused the greatest damage in FRO cells, a modest effect in NPA and WRO, and only minimal change in B-CPAP. The combined effect was most demonstrable in wells treated with Dox and radioiodine, whereas the addition of CDDP or 5-FU had marginal or insignificant merit, respectively. In FRO cells, half-lethal doses of the above mentioned CDDP, Dox, and 5-FU, when used together with 14.8 MBq/ml I-131, reduced cell survival to 54.5%, 29.4% and 33.4%, respectively, vs. 60.2% with radioiodine alone. In vitro, clinical concentrations of Dox can accelerate the killing of thyroid cancer cells by radioiodine. These favorable experimental results warrant future studies to evaluate whether this new bidisciplinary approach is clinically relevant and feasible. (author)

  17. A robust evaluation of sustainability initiatives with analytic network process (ANP)

    OpenAIRE

    Lanndon Ocampo; Christine Omela Ocampo

    2015-01-01

    This paper presents a methodology on evaluating sustainable manufacturing initiatives using analytic network process (ANP) as its base.The evaluation method is anchored on the comprehensive sustainable manufacturing framework proposed recently in literature. A numerical example that involves an evaluation of five sustainable manufacturing initiatives is shown in this work. Results show that sustainable manufacturing implies enhancing customer and community well-being by means of addressing en...

  18. Advanced Topics in Emergency Medicine: Curriculum Development and Initial Evaluation

    Directory of Open Access Journals (Sweden)

    Sorabh Khandelwal

    2011-05-01

    Full Text Available Background: Emergency medicine (EM is a young specialty and only recently has a recommended medical student curriculum been developed. Currently, many schools do not require students to complete a mandatory clerkship in EM, and if one is required, it is typically an overview of the specialty. Objectives: We developed a 10-month longitudinal elective to teach subject matter and skills in EM to fourth-year medical students interested in the specialty. Our goal was producing EM residents with the knowledge and skills to excel at the onset of their residency. We hoped to prove that students participating in this rigorous 10-month longitudinal EM elective would feel well prepared for residency. Methods: We studied the program with an end-of-the-year, Internet-based, comprehensive course evaluation completed by each participant of the first 2 years of the course. Graduates rated each of the course components by using a 5-point Likert format from ‘‘strongly disagree’’ to ‘‘strongly agree,’’ either in terms of whether the component was beneficial to them or whether the course expectations were appropriate, or their perceptions related to the course. Results: Graduates of this elective have reported feeling well prepared to start residency. The resident-led teaching shifts, Advanced Pediatric Life Support certification, Grand Rounds presentations, Advanced Cardiovascular Life Support proficiency testing, and ultrasound component, were found to be beneficial by all students. Conclusions: Our faculty believes that participating students will be better prepared for an EM residency than those students just completing a 1-month clerkship. Our data, although limited, lead us to believe that a longitudinal, immersion-type experience assists fourth-year medical students in preparation for residency. [West J Emerg Med. 2011;12(4:543–550.

  19. Endothelial cell-initiated signaling promotes the survival and self-renewal of cancer stem cells

    Science.gov (United States)

    Krishnamurthy, Sudha; Dong, Zhihong; Vodopyanov, Dmitry; Imai, Atsushi; Helman, Joseph I.; Prince, Mark E.; Wicha, Max S.; Nör, Jacques E.

    2010-01-01

    Recent studies have demonstrated that cancer stem cells play an important role in the pathobiology of head and neck squamous cell carcinomas (HNSCC). However, little is known about functional interactions between head and neck cancer stem-like cells (CSC) and surrounding stromal cells. Here, we used Aldehyde Dehydrogenase activity and CD44 expression to sort putative stem cells from primary human HNSCC. Implantation of 1,000 CSC (ALDH+CD44+Lin−) led to tumors in 13 (out of 15) mice, while 10,000 non-cancer stem cells (NCSC; ALDH−CD44−Lin−) resulted in 2 tumors in 15 mice. These data demonstrated that ALDH and CD44 select a sub-population of cells that are highly tumorigenic. The ability to self-renew was confirmed by the observation that ALDH+CD44+Lin− cells sorted from human HNSCC formed more spheroids (orospheres) in 3-D agarose matrices or ultra-low attachment plates than controls and were serially passaged in vivo. We observed that approximately 80% of the CSC were located in close proximity (within 100-µm radius) of blood vessels in human tumors, suggesting the existence of perivascular niches in HNSCC. In vitro studies demonstrated that endothelial cell-secreted factors promoted self-renewal of CSC, as demonstrated by the upregulation of Bmi-1 expression and the increase in the number of orospheres as compared to controls. Notably, selective ablation of tumor-associated endothelial cells stably transduced with a caspase-based artificial death switch (iCaspase-9) caused a marked reduction in the fraction of CSC in xenograft tumors. Collectively, these findings indicate that endothelial cell-initiated signaling can enhance the survival and self-renewal of head and neck cancer stem cells. PMID:21098716

  20. Initial Evaluation of a New Electromechanical Cooler for Safeguards Applications

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, RL

    2002-10-21

    The use of liquid nitrogen (LN{sub 2}) constitutes the current state of the art in cryogenic cooling for high-purity germanium (HPGe) detectors, which are widely used for {gamma}-ray and characteristic X-ray spectroscopy because of their excellent energy discrimination. Use of LN{sub 2} requires a liquid nitrogen supply, cumbersome storage tanks and plumbing, and the frequent attention of personnel to be sure that nitrogen levels are sufficient to maintain the detectors at a sufficiently low operating temperature. Safety hazards also are associated with the use of LN{sub 2}, both because of the potential for severe frostbite on exposure to skin and because it displaces ambient oxygen when it evaporates in closed spaces. Existing electromechanical coolers have, until now, been more expensive to procure and maintain than LN{sub 2} systems. Performance and reliability have also been serious issues because of microphonic degradation of photon energy peak resolution and cooler failures due to compressor oil becoming entrained in the refrigerant. This report describes the results of tests of a new HPGe detector cooling technology, the PerkinElmer ORTEC{reg_sign} Products X-Cooler{trademark} that, according to the manufacturer, significantly reduces the lifetime cost of the cooling system without degradation of the output signal. The manufacturer claims to have overcome cost, performance and reliability problems of older-generation electromechanical coolers, but the product has no significant history of use, and this project is the first independent evaluation of its performance for Total cost savings for the DOE and other agencies that use HPGe systems extensively for safeguards monitoring is expected to be quite significant if the new electromechanical cooler technology is shown to be reliable and if performance characteristics indicate its usefulness for this application. The technology also promises to make HPGe monitoring, characterization and detection available for

  1. Local calcium elevation and cell elongation initiate guided motility in electrically stimulated osteoblast-like cells.

    Directory of Open Access Journals (Sweden)

    Nurdan Ozkucur

    Full Text Available BACKGROUND: Investigation of the mechanisms of guided cell migration can contribute to our understanding of many crucial biological processes, such as development and regeneration. Endogenous and exogenous direct current electric fields (dcEF are known to induce directional cell migration, however the initial cellular responses to electrical stimulation are poorly understood. Ion fluxes, besides regulating intracellular homeostasis, have been implicated in many biological events, including regeneration. Therefore understanding intracellular ion kinetics during EF-directed cell migration can provide useful information for development and regeneration. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the initial events during migration of two osteogenic cell types, rat calvarial and human SaOS-2 cells, exposed to strong (10-15 V/cm and weak (< or = 5 V/cm dcEFs. Cell elongation and perpendicular orientation to the EF vector occurred in a time- and voltage-dependent manner. Calvarial osteoblasts migrated to the cathode as they formed new filopodia or lamellipodia and reorganized their cytoskeleton on the cathodal side. SaOS-2 cells showed similar responses except towards the anode. Strong dcEFs triggered a rapid increase in intracellular calcium levels, whereas a steady state level of intracellular calcium was observed in weaker fields. Interestingly, we found that dcEF-induced intracellular calcium elevation was initiated with a local rise on opposite sides in calvarial and SaOS-2 cells, which may explain their preferred directionality. In calcium-free conditions, dcEFs induced neither intracellular calcium elevation nor directed migration, indicating an important role for calcium ions. Blocking studies using cadmium chloride revealed that voltage-gated calcium channels (VGCCs are involved in dcEF-induced intracellular calcium elevation. CONCLUSION/SIGNIFICANCE: Taken together, these data form a time scale of the morphological and physiological

  2. Cell wall synthesis and initiation of deoxyribonucleic acid replication in Bacillus subtilis.

    OpenAIRE

    Sandler, N.; Keynan, A

    1981-01-01

    We have observed a connection between cell wall synthesis and the initiation of chromosome replication in Bacillus subtilis. Initiation of chromosome replication was prevented in synchronous cultures in the presence of the cell wall synthesis inhibitor vancomycin. When vancomycin was added to the cultures after initiation of chromosome replication, one round of replication was completed but no reinitiation occurred. Similar results were obtained when cell wall synthesis was inhibited by risto...

  3. Characterization of human embryonic stem cell lines by the International Stem Cell Initiative

    Czech Academy of Sciences Publication Activity Database

    Adewumi, O.; Aflatoonian, B.; Ahrlund-Richter, L.; Amit, M.; Andrews, P.W.; Beighton, G.; Bello, P.A.; Benvenisty, N.; Berry, L.S.; Bevan, S.; Blum, B.; Brooking, J.; Chen, K.G.; Choo, A.B.H.; Churchill, G.A.; Corbel, M.; Damjanov, I.; Draper, J.S.; Dvořák, Petr; Emanuelsson, K.; Fleck, R.A.; Ford, A.; Gertow, K.; Gertsenstein, M.; Gokhale, P.J.; Hamilton, R.S.; Hampl, Aleš; Healy, L.E.; Hovatta, O.; Hyllner, J.; Imreh, M.P.; Itskovitz-Eldor, J.; Jackson, J.; Johnson, J.L.; Jones, M.; Kee, K.; King, B.L.; Knowles, B.B.; Lako, M.; Lebrin, F.; Mallon, B.S.; Manning, D.; Mayshar, Y.; Mckay, D.G.; Michalska, A.E.; Mikkola, M.; Mileikovsky, M.; Minger, S.L.; Moore, H.D.; Mummery, Ch.L.; Nagy, A.; Nakutsuji, N.; O´Brien, C.M.; Oh, S.K.W.; Olsson, C.; Otonkoski, T.; Park, K.Y.; Passier, R.; Patel, H.; Patel, M.; Pedersen, R.; Pera, M.F.; Piekarczyk, M.S.; Pera, R.A.P.; Reubinoff, B.E.; Robins, A.J.; Rossant, J.; Rugg-Gunn, P.; Schulz, T.C.; Semb, H.; Sherrer, E.S.; Siemen, H.; Stacey, G.N.; Stojkovic, M.; Suemori, H.; Szatkiewicz, J.; Turetsky, T.; Tuuri, T.; Van den Brink, S.; Vintersten, K.; Vuoristo, S.; Ward, D.; Weaver, T.A.; Young, L.A.; Zhang, W.

    2007-01-01

    Roč. 25, č. 7 (2007), s. 803-816. ISSN 1087-0156 R&D Projects: GA MŠk 1M0538; GA ČR GA301/05/0463; GA ČR GA305/05/0434 Institutional research plan: CEZ:AV0Z50390512 Keywords : International Stem Cell Initiative Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 22.848, year: 2007

  4. Development of cancer-initiating cells and immortalized cells with genomic instability.

    Science.gov (United States)

    Yoshioka, Ken-Ichi; Atsumi, Yuko; Nakagama, Hitoshi; Teraoka, Hirobumi

    2015-03-26

    Cancers that develop after middle age usually exhibit genomic instability and multiple mutations. This is in direct contrast to pediatric tumors that usually develop as a result of specific chromosomal translocations and epigenetic aberrations. The development of genomic instability is associated with mutations that contribute to cellular immortalization and transformation. Cancer occurs when cancer-initiating cells (CICs), also called cancer stem cells, develop as a result of these mutations. In this paper, we explore how CICs develop as a result of genomic instability, including looking at which cancer suppression mechanisms are abrogated. A recent in vitro study revealed the existence of a CIC induction pathway in differentiating stem cells. Under aberrant differentiation conditions, cells become senescent and develop genomic instabilities that lead to the development of CICs. The resulting CICs contain a mutation in the alternative reading frame of CDKN2A (ARF)/p53 module, i.e., in either ARF or p53. We summarize recently established knowledge of CIC development and cellular immortality, explore the role of the ARF/p53 module in protecting cells from transformation, and describe a risk factor for genomic destabilization that increases during the process of normal cell growth and differentiation and is associated with the downregulation of histone H2AX to levels representative of growth arrest in normal cells. PMID:25815132

  5. Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division.

    Science.gov (United States)

    Xin, Hong-Wu; Hari, Danielle M; Mullinax, John E; Ambe, Chenwi M; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J; Wiegand, Gordon W; Garfield, Susan H; Thorgeirsson, Snorri S; Avital, Itzhak

    2012-04-01

    Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. PMID:22331764

  6. Tumor-Initiating and -Propagating Cells: Cells That We Would to Identify and Control

    Directory of Open Access Journals (Sweden)

    Berit Bølge Tysnes

    2010-07-01

    Full Text Available Identification of the cell types capable of initiating and sustaining growth of the neoplastic clone in vivo is a fundamental problem in cancer research. It is likely that tumor growth can be sustained both by rare cancer stem-like cells and selected aggressive clones and that the nature of the mutations, the cell of origin, and its environment will contribute to tumor propagation. Genomic instability, suggested as a driving force in tumorigenesis, may be induced by genetic and epigenetic changes. The feature of self-renewal in stem cells is shared with tumor cells, and deviant function of the stem cell regulatory networks may, in complex ways, contribute to malignant transformation and the establishment of a cancer stem cell-like phenotype. Understanding the nature of the more quiescent cancer stem-like cells and their niches has the potential to develop novel cancer therapeutic protocols including pharmacological targeting of self-renewal pathways. Drugs that target cancer-related inflammation may have the potential to reeducate a tumor-promoting microenvironment. Because most epigenetic modifications may be reversible, DNA methylation and histone deacetylase inhibitors can be used to induce reexpression of genes that have been silenced epigenetically. Design of therapies that eliminate cancer stem-like cells without eliminating normal stem cells will be important. Further insight into the mechanisms by which pluripotency transcription factors (e.g., OCT4, SOX2, and Nanog, polycomb repressive complexes and microRNA balance selfrenewal and differentiation will be essential for our understanding of both embryonic differentiation and human carcinogenesis and for the development of new treatment strategies.

  7. Tumor-initiating and -propagating cells: cells that we would like to identify and control.

    Science.gov (United States)

    Tysnes, Berit Bølge

    2010-07-01

    Identification of the cell types capable of initiating and sustaining growth of the neoplastic clone in vivo is a fundamental problem in cancer research. It is likely that tumor growth can be sustained both by rare cancer stem-like cells and selected aggressive clones and that the nature of the mutations, the cell of origin, and its environment will contribute to tumor propagation. Genomic instability, suggested as a driving force in tumorigenesis, may be induced by genetic and epigenetic changes. The feature of self-renewal in stem cells is shared with tumor cells, and deviant function of the stem cell regulatory networks may, in complex ways, contribute to malignant transformation and the establishment of a cancer stem cell-like phenotype. Understanding the nature of the more quiescent cancer stem-like cells and their niches has the potential to develop novel cancer therapeutic protocols including pharmacological targeting of self-renewal pathways. Drugs that target cancer-related inflammation may have the potential to reeducate a tumor-promoting microenvironment. Because most epigenetic modifications may be reversible, DNA methylation and histone deacetylase inhibitors can be used to induce reexpression of genes that have been silenced epigenetically. Design of therapies that eliminate cancer stem-like cells without eliminating normal stem cells will be important. Further insight into the mechanisms by which pluripotency transcription factors (e.g., OCT4, SOX2, and Nanog), polycomb repressive complexes and microRNA balance selfrenewal and differentiation will be essential for our understanding of both embryonic differentiation and human carcinogenesis and for the development of new treatment strategies. PMID:20651980

  8. Tumor-Initiating and -Propagating Cells: Cells That We Would Like to Identify and Control1

    Science.gov (United States)

    Tysnes, Berit Bølge

    2010-01-01

    Identification of the cell types capable of initiating and sustaining growth of the neoplastic clone in vivo is a fundamental problem in cancer research. It is likely that tumor growth can be sustained both by rare cancer stem-like cells and selected aggressive clones and that the nature of the mutations, the cell of origin, and its environment will contribute to tumor propagation. Genomic instability, suggested as a driving force in tumorigenesis, may be induced by genetic and epigenetic changes. The feature of self-renewal in stem cells is shared with tumor cells, and deviant function of the stem cell regulatory networks may, in complex ways, contribute to malignant transformation and the establishment of a cancer stem cell-like phenotype. Understanding the nature of the more quiescent cancer stem-like cells and their niches has the potential to develop novel cancer therapeutic protocols including pharmacological targeting of self-renewal pathways. Drugs that target cancer-related inflammation may have the potential to reeducate a tumor-promoting microenvironment. Because most epigenetic modifications may be reversible, DNA methylation and histone deacetylase inhibitors can be used to induce reexpression of genes that have been silenced epigenetically. Design of therapies that eliminate cancer stem-like cells without eliminating normal stem cells will be important. Further insight into the mechanisms by which pluripotency transcription factors (e.g., OCT4, SOX2, and Nanog), polycomb repressive complexes and microRNA balance selfrenewal and differentiation will be essential for our understanding of both embryonic differentiation and human carcinogenesis and for the development of new treatment strategies. PMID:20651980

  9. Isolation and initial characterization of thermoresistant RIF tumor cell strains

    International Nuclear Information System (INIS)

    Heat-resistant cell strains were obtained from RIF-1 mouse tumor cells by repeated heatings of cells derived from survivors of previous heating cycles (60 min; 450C). Twenty thermally resistant (TR) strains were derived from single cells that had survived 11 heating and regrowth cycles. These were then analyzed for appropriate characteristics in vitro and in vivo. In vitro we looked for: marked heat resistance; high plating efficiency; growth rate similar to that of RIF-1 cells; and no obvious morphological abnormalities. In syngeneic hosts, we looked for: ability of the cells to form tumors whose growth rates were similar to that of RIF-1 tumors; high cellular heat resistance; good plating efficiency of tumor-derived cells; and low immunogenicity. Five strains having these desired characteristics were analyzed for survival kinetics. The heat-resistant phenotype was found to be stable in vitro, although partial reversion in vivo was seen occasionally. The break in the Arrhenius plot was found to occur at 450C in TR strains versus 430C in RIF-1. All TR strains and the RIF-1 line developed similar levels of thermotolerance (as defined by slope ratios) when given isosurvival heat exposures. X-ray responses of TR and RIF-1 cells were indistinguishable both with respect to survival and to heat-induced radiosensitization. While the number of live cells required to give tumor takes in 50% of the recipients for TR strains was appreciably higher than that for RIF-1 cells, radiation-killed cells from none of the strains were able to immunize efficiently against subsequent challenges by live cells

  10. Constraints on plate tectonics initiation from scaling laws for single-cell convection

    Science.gov (United States)

    Wong, Teresa; Solomatov, Viatcheslav S.

    2016-08-01

    The Earth is the only planet known to have plate tectonics, while other planets are covered with a stagnant lid. On the Earth, the initiation of subduction, which is thought to be the fundamental process for plate tectonics initiation, is caused not only by the negative buoyancy of the lithosphere but also by the forces from plate motions. However, for planets which do not have plate tectonics, the very first episode of lithospheric failure has to be caused by forces other than plate motions. Sublithospheric convection has been proposed as a possible mechanism that provides lithospheric instability through inducing stresses in the lithosphere, and lithospheric failure can occur when the yield stress is below a critical value. We test the applicability of scaling laws for the critical yield stress obtained in single-cell convection simulations to strongly time-dependent multi-cell systems. We show that with an appropriate choice of characteristic aspect ratio for the convective system, the scaling laws from single-cell simulations can be used to evaluate the conditions on the terrestrial planets in the inner Solar System for plate tectonics to exist. In agreement with previous studies, the estimated values for critical yield stress and coefficient of friction are much lower than the expected values for the Earth's lithosphere.

  11. Lung cancer-initiating cells: a novel target for cancer therapy

    OpenAIRE

    Morrison, Brian J.; Morris, John C.; Steel, Jason C

    2013-01-01

    Lung cancer is a major public health problem causing more deaths than any other cancer. A better understanding of the biology of this disease and improvements in treatment are greatly needed. Increasing evidence supports the concept that a rare and specialized population of cancer cells, so-called cancer-initiating cells with stem cell-like characteristics, is responsible for tumor growth, maintenance, and recurrence. Cancer-initiating cells also exhibit characteristics that render them resis...

  12. Cancer stem cells, cancer-initiating cells and methods for their detection.

    Science.gov (United States)

    Akbari-Birgani, Shiva; Paranjothy, Ted; Zuse, Anna; Janikowski, Tomasz; Cieślar-Pobuda, Artur; Likus, Wirginia; Urasińska, Elżbieta; Schweizer, Frank; Ghavami, Saeid; Klonisch, Thomas; Łos, Marek J

    2016-05-01

    The cancer stem cell (CSC) hypothesis considers CSCs as the main culprits of tumor initiation, propagation, metastasis and therapy failure. CSCs represent a minority subpopulation of cells within a tumor. Their detection, characterization and monitoring are crucial steps toward a better understanding of the biological roles of these special cells in the development and propagation of tumors which, in turn, improves clinical reasoning and treatment options. Nowadays, in vitro and in vivo assays are available that address the self-renewal and differentiation potential of CSCs, and advanced in vivo molecular imaging technology facilitates the detection and provides an unprecedented in vivo observation platform to study the behavior of CSCs in their natural environment. Here, we provide a brief overview of CSCs and describe modern cellular models and labeling techniques to study and trace CSCs. PMID:26976692

  13. Seismic evaluation of a hot cell structure

    International Nuclear Information System (INIS)

    The evaluation of the structural capacity of and the seismic demand on an existing hot cell structure in a nuclear facility is described. An ANSYS finite-element model of the cell was constructed, treating the walls as plates and the floor and ceiling as a system of discrete beams. A modal analysis showed that the fundamental frequencies of the cell walls lie far above the earthquake frequency range. An equivalent static analysis of the structure was performed. Based on the analysis it was demonstrated that the hot cell structure, would readily withstand the evaluation basis earthquake

  14. Evaluation of core-debris accommodation within inner containment cell

    International Nuclear Information System (INIS)

    A reactor cell concept for permanent retention has been developed based on evaluations of core debris melt penetration into containment structures, material interactions, pressure buildup and hydrogen concentration in the containment. The selected reactor cell concept includes a protective layer of MgO on the reactor cell floor, a graphite layer as the cell wall liner protection, and insulating firebrick to keep the cell concrete structures at an acceptable temperature level. To determine the feasibility of long-term/permanent retention of core debris, parametric studies were performed with the modified GROWS-2 code and the CACECO code to assess the range of debris penetration, containment responses and cooling requirements. Debris penetration into a MgO delay bed was shown to be very sensitive to the initial debris layer thickness. Long-term debris retention capability can be enhanced by preventing early sodium boil-off from the reactor cell

  15. A systematic analysis of cell cycle regulators in yeast reveals that most factors act independently of cell size to control initiation of division.

    Directory of Open Access Journals (Sweden)

    Scott A Hoose

    Full Text Available Upstream events that trigger initiation of cell division, at a point called START in yeast, determine the overall rates of cell proliferation. The identity and complete sequence of those events remain unknown. Previous studies relied mainly on cell size changes to identify systematically genes required for the timely completion of START. Here, we evaluated panels of non-essential single gene deletion strains for altered DNA content by flow cytometry. This analysis revealed that most gene deletions that altered cell cycle progression did not change cell size. Our results highlight a strong requirement for ribosomal biogenesis and protein synthesis for initiation of cell division. We also identified numerous factors that have not been previously implicated in cell cycle control mechanisms. We found that CBS, which catalyzes the synthesis of cystathionine from serine and homocysteine, advances START in two ways: by promoting cell growth, which requires CBS's catalytic activity, and by a separate function, which does not require CBS's catalytic activity. CBS defects cause disease in humans, and in animals CBS has vital, non-catalytic, unknown roles. Hence, our results may be relevant for human biology. Taken together, these findings significantly expand the range of factors required for the timely initiation of cell division. The systematic identification of non-essential regulators of cell division we describe will be a valuable resource for analysis of cell cycle progression in yeast and other organisms.

  16. A Plan for the Evaluation of California's Class Size Reduction Initiative.

    Science.gov (United States)

    Kirst, Michael; Bomstedt, George; Stecher, Brian

    In July 1996, California began its Class Size Reduction (CSR) Initiative. To gauge the effectiveness of this initiative, an analysis of its objectives and an overview of proposed strategies for evaluating CSR are presented here. An outline of the major challenges that stand between CSR and its mission are provided. These include logistical…

  17. Teledyne Energy Systems, Inc., Proton Exchange Member (PEM) Fuel Cell Engineering Model Powerplant. Test Report: Initial Benchmark Tests in the Original Orientation

    Science.gov (United States)

    Loyselle, Patricia; Prokopius, Kevin

    2011-01-01

    Proton Exchange Membrane (PEM) fuel cell technology is the leading candidate to replace the alkaline fuel cell technology, currently used on the Shuttle, for future space missions. During a 5-yr development program, a PEM fuel cell powerplant was developed. This report details the initial performance evaluation test results of the powerplant.

  18. Oncogenic Kras initiates leukemia in hematopoietic stem cells.

    OpenAIRE

    Amit J Sabnis; Cheung, Laurene S.; Monique Dail; Hio Chung Kang; Marianne Santaguida; Hermiston, Michelle L.; Emmanuelle Passegué; Kevin Shannon; Braun, Benjamin S.

    2009-01-01

    Author Summary Ras proteins act as molecular switches that relay growth signals from outside the cell. This mechanism is often subverted in cancer, and Ras proteins are activated directly by RAS gene mutations in approximately one-third of human malignancies. We have modeled this in mice engineered to have a Ras mutation. These mice develop a disease similar to chronic leukemias in humans called myeloproliferative disorders. It is marked by a fatal accumulation of mature and immature cells in...

  19. Oncogenic Kras Initiates Leukemia in Hematopoietic Stem Cells

    OpenAIRE

    Sabnis, Amit J; Cheung, Laurene S.; Dail, Monique; Kang, Hio Chung; Santaguida, Marianne; Hermiston, Michelle L.; Passegué, Emmanuelle; Shannon, Kevin; Braun, Benjamin S.

    2009-01-01

    Author Summary Ras proteins act as molecular switches that relay growth signals from outside the cell. This mechanism is often subverted in cancer, and Ras proteins are activated directly by RAS gene mutations in approximately one-third of human malignancies. We have modeled this in mice engineered to have a Ras mutation. These mice develop a disease similar to chronic leukemias in humans called myeloproliferative disorders. It is marked by a fatal accumulation of mature and immature cells in...

  20. The phytoalexin resveratrol regulates the initiation of hypersensitive cell death in Vitis cell.

    Directory of Open Access Journals (Sweden)

    Xiaoli Chang

    Full Text Available Resveratrol is a major phytoalexin produced by plants in response to various stresses and promotes disease resistance. The resistance of North American grapevine Vitis rupestris is correlated with a hypersensitive reaction (HR, while susceptible European Vitis vinifera cv. 'Pinot Noir' does not exhibit HR, but expresses basal defence. We have shown previously that in cell lines derived from the two Vitis species, the bacterial effector Harpin induced a rapid and sensitive accumulation of stilbene synthase (StSy transcripts, followed by massive cell death in V. rupestris. In the present work, we analysed the function of the phytoalexin resveratrol, the product of StSy. We found that cv. 'Pinot Noir' accumulated low resveratrol and its glycoside trans-piceid, whereas V. rupestris produced massive trans-resveratrol and the toxic oxidative δ-viniferin, indicating that the preferred metabolitism of resveratrol plays role in Vitis resistance. Cellular responses to resveratrol included rapid alkalinisation, accumulation of pathogenesis-related protein 5 (PR5 transcripts, oxidative burst, actin bundling, and cell death. Microtubule disruption and induction of StSy were triggered by Harpin, but not by resveratrol. Whereas most responses proceeded with different amplitude for the two cell lines, the accumulation of resveratrol, and the competence for resveratrol-induced oxidative burst differed in quality. The data lead to a model, where resveratrol, in addition to its classical role as antimicrobial phytoalexin, represents an important regulator for initiation of HR-related cell death.

  1. Sustainable test cell : performance evaluation

    OpenAIRE

    Silva, Pedro Correia Pereira da; Bragança, L.; Mendonça, Paulo; Almeida, Manuela Guedes de

    2006-01-01

    Energy is one of the main causes of the environmental pollution. In the European Union, buildings are responsible for 40% of the final energy demand and 1/3 of the emissions of greenhouse gases. Therefore, in order to promote the energy consumption reduction, it is fundamental to employ sustainable development principles in the construction sector. In order to demonstrate and show the potentialities of Sustainable building technologies two Test Cells were built. Comparing the solutions obtain...

  2. DNA repair: the culprit for tumor-initiating cell survival?

    OpenAIRE

    Mathews, Lesley A.; Cabarcas, Stephanie M.; Farrar, William L.

    2011-01-01

    The existence of “tumor-initiating cells” (TICs) has been a topic of heated debate for the last few years within the field of cancer biology. Their continuous characterization in a variety of solid tumors has led to an abundance of evidence supporting their existence. TICs are believed to be responsible for resistance against conventional treatment regimes of chemotherapy and radiation, ultimately leading to metastasis and patient demise. This review summarizes DNA repair mechanism(s) and the...

  3. Initial results for the silicon monolithically interconnected solar cell product

    Science.gov (United States)

    Dinetta, L. C.; Shreve, K. P.; Cotter, J. E.; Barnett, A. M.

    1995-01-01

    This proprietary technology is based on AstroPower's electrostatic bonding and innovative silicon solar cell processing techniques. Electrostatic bonding allows silicon wafers to be permanently attached to a thermally matched glass superstrate and then thinned to final thicknesses less than 25 micron. These devices are based on the features of a thin, light-trapping silicon solar cell: high voltage, high current, light weight (high specific power) and high radiation resistance. Monolithic interconnection allows the fabrication costs on a per watt basis to be roughly independent of the array size, power or voltage, therefore, the cost effectiveness to manufacture solar cell arrays with output powers ranging from milliwatts up to four watts and output voltages ranging from 5 to 500 volts will be similar. This compares favorably to conventionally manufactured, commercial solar cell arrays, where handling of small parts is very labor intensive and costly. In this way, a wide variety of product specifications can be met using the same fabrication techniques. Prototype solar cells have demonstrated efficiencies greater than 11%. An open-circuit voltage of 5.4 volts, fill factor of 65%, and short-circuit current density of 28 mA/sq cm at AM1.5 illumination are typical. Future efforts are being directed to optimization of the solar cell operating characteristics as well as production processing. The monolithic approach has a number of inherent advantages, including reduced cost per interconnect and increased reliability of array connections. These features make this proprietary technology an excellent candidate for a large number of consumer products.

  4. Containment performance evaluation for the GESSAR-II plant for seismic initiating events

    International Nuclear Information System (INIS)

    As a part of the overall effort undertaken by Brookhaven National Laboratory (BNL) to review the GESSAR-II probabilistic risk assessment, an independent containment performance evaluation was performed using the containment event tree approach. This evaluation focused principally on those accident sequences which are initiated by seismic events. This paper reports the findings of this study. 1 ref

  5. Evaluating human cancer cell metastasis in zebrafish

    International Nuclear Information System (INIS)

    In vivo metastasis assays have traditionally been performed in mice, but the process is inefficient and costly. However, since zebrafish do not develop an adaptive immune system until 14 days post-fertilization, human cancer cells can survive and metastasize when transplanted into zebrafish larvae. Despite isolated reports, there has been no systematic evaluation of the robustness of this system to date. Individual cell lines were stained with CM-Dil and injected into the perivitelline space of 2-day old zebrafish larvae. After 2-4 days fish were imaged using confocal microscopy and the number of metastatic cells was determined using Fiji software. To determine whether zebrafish can faithfully report metastatic potential in human cancer cells, we injected a series of cells with different metastatic potential into the perivitelline space of 2 day old embryos. Using cells from breast, prostate, colon and pancreas we demonstrated that the degree of cell metastasis in fish is proportional to their invasion potential in vitro. Highly metastatic cells such as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the body of the fish after only 24–48 hours. Importantly, cells that are not invasive in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in vivo, and in zebrafish these cells show limited spread throughout the zebrafish body compared with the highly metastatic parental cells. Further, knockdown of WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in vivo also results in suppression of metastasis in zebrafish. In a cancer progression model involving normal MCF10A breast epithelial cells, the degree of invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a modified version of Fiji software, it is possible to quantify individual metastatic cells in the transparent larvae to correlate with

  6. Bmi1 reprograms CML B-lymphoid progenitors to become B-ALL–initiating cells

    OpenAIRE

    Sengupta, Amitava; Ficker, Ashley M.; Dunn, Susan K.; Madhu, Malav; Cancelas, Jose A.

    2012-01-01

    The characterization and targeting of Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL)–initiating cells remains unresolved. Expression of the polycomb protein Bmi1 is up-regulated in patients with advanced stages of chronic myelogenous leukemia (CML). We report that Bmi1 transforms and reprograms CML B-lymphoid progenitors into stem cell leukemia (Scl) promoter-driven, self-renewing, leukemia-initiating cells to result in B-lymphoid leukemia (B-ALL) in vivo. In vitro,...

  7. Antisense oligonucleotide targeting at the initiator of hTERT arrests growth of hepatoma cells

    Institute of Scientific and Technical Information of China (English)

    Su-Xia Liu; Wen-Sheng Sun; Ying-Lin Cao; Chun-Hong Ma; Li-Hui Han; Li-Ning Zhang; Zhen-Guang Wang; Fa-Liang Zhu

    2004-01-01

    AIM: To evaluate the inhibitory effect of antisense phosphorothioate oligonucleotide (asON) complementary to the initiator of human telomerase catalytic subunit (hTERT)on the growth of hepatoma cells.METHODS: The as-hTERT was synthesized by using a DNA synthesizer. HepG2.2.15 cells were treated with ashTERT at the concentration of 10 μmol/L. After 72 h, these cells were obtained for detecting growth inhibition,telomerase activity using the methods of MTT, TRAP-PCR-ELISA, respectively. BALB/c(nu/nu) mice were injected HepG2.2.15 cells and a human-nude mice model was obtained. There were three groups for anti-tumor activity study. Once tumors were established, these animals in the first group were administered as-hTERT and saline.Apoptosis of tumor cells was detected by FCM. In the 2nd group, the animals were injected HepG2.2.15 cells together with as-hTERT. In the third group, the animals were given as-hTERT 24 hours postinjection of HepG2.2.15 cells. The anti-HBV effects were assayed with ELISA ih vitro and in vivo.RESULTS: Growth inhibition was observed in cells treated with as-hTERT ih vitro. A significant different in the value of A570-A630 was found between cells treated with as-hTERT and control (P<0.01) by MTT method. The telomerase activity of tumor cells treated with as-hTERT was reduced,the value of A450 nm was 0.42 compared to control (1,49)with TRAP-PCR-ELISA. The peak of apoptosis in tumor cells given as-hTERT was 21. 12%, but not seen in saline-treated control. A prolonged period of carcinogenesis was observed in the second and third group animals. There was inhibitory effect on the expression of HBsAg and HBeAg ih vivo and in vitro.CONCLUSION: As-hTERT has an anti-tumor activity, which may be useful for gene therapy of tumors.

  8. Changes in inositol phosphates in wild carrot cells upon initiation of cell wall digestion

    International Nuclear Information System (INIS)

    Previous studies have shown that inositol trisphosphate (IP3) stimulated 45Ca+2 efflux from fusogenic carrot protoplasts and it was suggested that IP3 may serve as a second messenger for the mobilization of intracellular Ca+2 in higher plant cells. To determine whether or not inositol phosphate metabolism changes in response to external stimuli, the cells were labeled with myo-[2-3H] inositol for 18 h and exposed to cell wall digestion enzymes, Driselase. The inositol phosphates were extracted with ice cold 10% TCA and separated by anion exchange chromatography. The radioactivity of the fraction that contained IP3 increased 2-3.8 fold and that which contained inositol bisphosphate increased 1.9-2.6 fold within 1.5 min of exposure to Driselase. After 6 min, the radioactivity of both fractions increased 6-7.7 fold and an increase in inositol monophosphate was observed. These data indicate that inositol phosphate metabolism is stimulated by Driselase and suggest polyphosphoinositide hydrolysis occurs upon initiation of cell wall digestion

  9. A quality improvement initiative project to evaluate a newborn hearing screening program in a Baby-Friendly Hospital Initiative setting

    Directory of Open Access Journals (Sweden)

    Stacey R. Lim

    2015-02-01

    Full Text Available Hearing loss present from birth can have a detrimental impact on later language and educational outcomes. Newborn hearing screening has allowed early identification and intervention of hearing loss, giving children the opportunity to develop age-appropriate language skills. The aim of this quality initiative study was to evaluate the quality of the newborn hearing screening program in the context of a newly implemented Baby-Friendly Hospital Initiative Program at Summa Health System Akron City Hospital. The goals were (1 to determine whether screening environment (mother’s room vs. nursery affected screening results, (2 to identify challenges and positive outcomes encountered by the audiologists, and (3 to ensure that Pass/Refer rates met state standards. A Quest Technologies sound level meter (Model 1800; St. Paul, MN, USA was used to measure noise levels in the nursery rooms where newborns were tested. The length of screening time was determined using a calibrated SP® Traceable® (ISO 17025 stopwatch (McGraw Park, IL, USA. Pass/Refer rates and observed challenges and benefits were noted. All well-baby infants born in the month of February 2013 (n = 101 were included, and Pass/Refer results were compared to those in years 2008-2012.Noise levels in the mother’s room did not appear to negatively affect the Pass/Refer rates. Some challenges were present, including interruptions and louder environmental noise. This protocol was considered appropriate for assessing a hearing screening program in a Baby-Friendly Hospital Initiative (BFHI setting.Benefits of performing hearing screening in the mother’s room included test transparency for parents and the ability to immediately discuss the results. Results obtained in the mother’s room were comparable to past results obtained in the nursery. Noise levels in the screening rooms and challenges should be noted, to ensure accuracy of screening results.

  10. Maintenance of Leukemia-Initiating Cells Is Regulated by the CDK Inhibitor Inca1

    OpenAIRE

    Bäumer, Nicole; Bäumer, Sebastian; Berkenfeld, Frank; Stehling, Martin; Köhler, Gabriele; Berdel, Wolfgang E.; Müller-Tidow, Carsten; Tschanter, Petra

    2014-01-01

    Functional differences between healthy progenitor and cancer initiating cells may provide unique opportunities for targeted therapy approaches. Hematopoietic stem cells are tightly controlled by a network of CDK inhibitors that govern proliferation and prevent stem cell exhaustion. Loss of Inca1 led to an increased number of short-term hematopoietic stem cells in older mice, but Inca1 seems largely dispensable for normal hematopoiesis. On the other hand, Inca1-deficiency enhanced cell cycling...

  11. Short Telomeres Initiate Telomere Recombination in Primary and Tumor Cells

    OpenAIRE

    Morrish, Tammy A.; Greider, Carol W

    2009-01-01

    Human tumors that lack telomerase maintain telomeres by alternative lengthening mechanisms. Tumors can also form in telomerase-deficient mice; however, the genetic mechanism responsible for tumor growth without telomerase is unknown. In yeast, several different recombination pathways maintain telomeres in the absence of telomerase-some result in telomere maintenance with minimal effects on telomere length. To examine non-telomerase mechanisms for telomere maintenance in mammalian cells, we us...

  12. Endothelial cells do not arise from tumor-initiating cells in human hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Conventional models of carcinogenesis suggest that tumors recruit blood vessel formation from normal host tissues. This concept has recently been challenged by prominent studies of glioblastoma, which suggest that intratumoral endothelial cells (ECs) may arise from cancer stem cells/tumor-initiating cells (TICs). Hepatocellular carcinoma (HCC) is a common, highly vascularized tumor with few effective therapies, against which anti-angiogenic strategies are being actively explored. TICs are felt to play a role in HCC pathobiology, but their contributions to tumor vasculature have not been studied. We examined human HCCs in settings that selected for tumor formation from functionally defined TICs, and in which the origin of intratumoral ECs from TICs as opposed to host tissues could be clearly distinguished. We generated HCC nodules in the livers of immunodeficient mice by intrasplenic injection of HCC cells from cell lines and patient specimens and studied the tumor ECs by immunohistochemistry for mouse and human markers. We then used immunohistochemistry for EC markers in combination with fluorescence in situ hybridization (FISH) for X and Y chromosomes to study the endothelium of recurrent HCC specimens resected from sex-mismatched liver allografts of patients who had undergone liver transplantation for HCC. We observed that all ECs in intrahepatic human HCC xenografts expressed mouse rather than human CD31. FISH analysis of recurrent HCCs resected from patients with sex-mismatched liver allografts revealed that all CD31+ and CD34+ intratumoral ECs originated from the donor allograft rather than the tumor. These observations suggest that the vasculature of human HCC arises from normal host tissues rather than from TICs, supporting ongoing efforts to target angiogenesis in HCC as it is currently understood, and suggesting that the contribution of TICs to the vasculature of other cancers is disease-specific

  13. Hydraulic Conductivity of Smooth Muscle Cell-Initiated Arterial Cocultures.

    Science.gov (United States)

    Mathura, Rishi A; Russell-Puleri, Sparkle; Cancel, Limary M; Tarbell, John M

    2016-05-01

    The purpose of the study was to examine the effects of arterial coculture conditions on the transport properties of several in vitro endothelial cell (EC)-smooth muscle cell (SMC)-porous filter constructs in which SMC were grown to confluence first and then EC were inoculated. This order of culturing simulates the environment of a blood vessel wall after endothelial layer damage due to stenting, vascular grafting or other vascular wall insult. For all coculture configurations examined, we observed that hydraulic conductivity (L p) values were significantly higher than predicted by a resistances-in-series (RIS) model accounting for the L p of EC and SMC measured separately. The greatest increases were observed when EC were plated directly on top of a confluent SMC layer without an intervening filter, presumably mediated by direct EC-SMC contacts that were observed under confocal microscopy. The results are the opposite of a previous study that showed L p was significantly reduced compared to an RIS model when EC were grown to confluency first. The physiological, pathophysiological and tissue engineering implications of these results are discussed. PMID:26265460

  14. Inhibition of Mouse Breast Tumor-Initiating Cells by Calcitriol and Dietary Vitamin D.

    Science.gov (United States)

    Jeong, Youngtae; Swami, Srilatha; Krishnan, Aruna V; Williams, Jasmaine D; Martin, Shanique; Horst, Ronald L; Albertelli, Megan A; Feldman, Brian J; Feldman, David; Diehn, Maximilian

    2015-08-01

    The anticancer actions of vitamin D and its hormonally active form, calcitriol, have been extensively documented in clinical and preclinical studies. However, the mechanisms underlying these actions have not been completely elucidated. Here, we examined the effect of dietary vitamin D and calcitriol on mouse breast tumor-initiating cells (TICs, also known as cancer stem cells). We focused on MMTV-Wnt1 mammary tumors, for which markers for isolating TICs have previously been validated. We confirmed that these tumors expressed functional vitamin D receptors and estrogen receptors (ER) and exhibited calcitriol-induced molecular responses including ER downregulation. Following orthotopic implantation of MMTV-Wnt1 mammary tumor cells into mice, calcitriol injections or a vitamin D-supplemented diet caused a striking delay in tumor appearance and growth, whereas a vitamin D-deficient diet accelerated tumor appearance and growth. Calcitriol inhibited TIC tumor spheroid formation in a dose-dependent manner in primary cultures and inhibited TIC self-renewal in secondary passages. A combination of calcitriol and ionizing radiation inhibited spheroid formation more than either treatment alone. Further, calcitriol significantly decreased TIC frequency as evaluated by in vivo limiting dilution analyses. Calcitriol inhibition of TIC spheroid formation could be overcome by the overexpression of β-catenin, suggesting that the inhibition of Wnt/β-catenin pathway is an important mechanism mediating the TIC inhibitory activity of calcitriol in this tumor model. Our findings indicate that vitamin D compounds target breast TICs reducing tumor-initiating activity. Our data also suggest that combining vitamin D compounds with standard therapies may enhance anticancer activity and improve therapeutic outcomes. PMID:25934710

  15. TTA school-based research consortium initiative, the evaluation, final report

    OpenAIRE

    Kushner, S.; Simons, H.; James, D; Jones, K; Yee, W C

    2001-01-01

    This is the final report of the evaluation of th School-Based Research Consortium Initiative which ran in England from 1998 to 2001. The initiative was sponsored via a public/private partnership between the Teacher Training Agency (TTA), a UK Government agency, and the Centre for British Teachers (CfBT), a private not-for-profit company. The aim of the initiative was to create local infrastructures of support and action for teachers to engage ‘in and with’ research. Those infrastructures wer...

  16. Initial interaction of herpes simplex virus with cells is binding to heparan sulfate.

    OpenAIRE

    WuDunn, D; Spear, P G

    1989-01-01

    We have shown that cell surface heparan sulfate serves as the initial receptor for both serotypes of herpes simplex virus (HSV). We found that virions could bind to heparin, a related glycosaminoglycan, and that heparin blocked virus adsorption. Agents known to bind to cell surface heparan sulfate blocked viral adsorption and infection. Enzymatic digestion of cell surface heparan sulfate but not of dermatan sulfate or chondroitin sulfate concomitantly reduced the binding of virus to the cells...

  17. Sternal metastasis as an initial presentation of renal cell carcinoma: a case report

    OpenAIRE

    Batista, Raquel Ribeiro; Marchiori, Edson; Takayassu, Tatiana Chinem; Cabral, Fernanda Caseira; Cabral, Rafael Ferracini; Zanetti, Gláucia

    2009-01-01

    Renal cell carcinoma accounts for 85% of all solid renal tumors in adults. Nearly one quarter of patients has distant metastasis at presentation while another 50% develop metastasis during follow-up. A small percentage of these are solitary metastasis. We report here a case of solitary bone sternal metastasis as an initial presentation of clear-cell renal cell carcinoma in a 56-year-old woman. The prognosis for patients with metastasized renal cell carcinoma is poor; treatment of metastasis i...

  18. Ultrastructure of cells in an initiating lateral root primordium of Raphanus sativus

    OpenAIRE

    F. Kadej; B. Rodkiewicz

    2015-01-01

    Lateral root primordia in Raphanus sativus had developed 10 hours after main root decapitation. The primordia consisted of three cell layers — basal layer continuous with the pericycle. The primordia were initiated by activated groups of pericycle cells. Inactive pericycle cells with a thin layer of parietal cytoplasme large central vacuole and well developed leucoplasts with starch grains were trans-formed into meristematic cells. During transformation the amount of cytoplasm and number of c...

  19. Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation

    Science.gov (United States)

    Marhavý, Peter; Montesinos, Juan Carlos; Abuzeineh, Anas; Van Damme, Daniel; Vermeer, Joop E.M.; Duclercq, Jerôme; Rakusová, Hana; Nováková, Petra; Friml, Jiři; Geldner, Niko; Benková, Eva

    2016-01-01

    To sustain a lifelong ability to initiate organs, plants retain pools of undifferentiated cells with a preserved proliferation capacity. The root pericycle represents a unique tissue with conditional meristematic activity, and its tight control determines initiation of lateral organs. Here we show that the meristematic activity of the pericycle is constrained by the interaction with the adjacent endodermis. Release of these restraints by elimination of endodermal cells by single-cell ablation triggers the pericycle to re-enter the cell cycle. We found that endodermis removal substitutes for the phytohormone auxin-dependent initiation of the pericycle meristematic activity. However, auxin is indispensable to steer the cell division plane orientation of new organ-defining divisions. We propose a dual, spatiotemporally distinct role for auxin during lateral root initiation. In the endodermis, auxin releases constraints arising from cell-to-cell interactions that compromise the pericycle meristematic activity, whereas, in the pericycle, auxin defines the orientation of the cell division plane to initiate lateral roots. PMID:26883363

  20. Context Information Based Initial Cell Search for Millimeter Wave 5G Cellular Networks

    OpenAIRE

    Abbas, Waqas Bin; Zorzi, Michele

    2016-01-01

    Millimeter wave (mmWave) communication is envisioned as a cornerstone to fulfill the data rate requirements for fifth generation (5G) cellular networks. In mmWave communication, beamforming is considered as a key technology to combat the high path-loss, and unlike in conventional microwave communication, beamforming may be necessary even during initial access/cell search. Among the proposed beamforming schemes for initial cell search, analog beamforming is a power efficient approach but suffe...

  1. An Evaluation of the Initial Year of Zero-Base Budgeting in the Federal Government

    OpenAIRE

    Virendra S. Sherlekar; Burton V. Dean

    1980-01-01

    This paper presents a comprehensive evaluation of the strengths and weaknesses of the Zero-Base Budgeting (ZBB) process during the initial year of its implementation in the Federal Government. The evaluation includes ten Departments and six agencies of the Federal Government representing 74 percent of the total budget authority of 560 billion dollars. It is based on the information received in responses from federal agencies to the Office of Management and Budget Eleven major criteria were fo...

  2. Self-Evaluation report of the Strategic Research Initiative: Designing Human Technologies, DHT (2013-2016)

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    2016-01-01

    This self-evaluation report, requested by the Pro-rector of Roskilde University, has been written by Jesper Simonsen. The report is presented in a dedicated template and describes and evaluates the strategic research initiative Designing Human Technologies (DHT). DHT was formally approved by the ...... Rectorship in February 2013. DHT was funded by Roskilde University with a 3,000,000 DKK grant for the period of 2013– 2015. In 2015 this was extended to June 2016....

  3. Comparative Evaluation of the Initial Corrosion of Four Brands of High Copper Dental Amalgams

    OpenAIRE

    V MORTAZAVI; Fathi MH.

    2004-01-01

    Statement of Problem: Many attempts have been made in order to evaluate the amalgam corrosion behavior as an indicator of biocompatibility. Purpose: The aim of this study was to evaluate and compare the initial corrosion of four different brands of dental amalgams. Materials and Methods: Four different types of commercial high copper dental amalgam were studied. A special mold was used and twenty-one samples of each type of commercial dental amalgams were prepared. X-ray diffraction technique...

  4. The intrusive growth of initial cells in re-arangement of cells in cambium of Tilia cordata Mill.

    Directory of Open Access Journals (Sweden)

    Wiesław Włoch

    2014-02-01

    Full Text Available In the cambium of linden producing wood with short period of grain inclination change (2-4 years, the intensive reorientation of cells takes place. This is possible mainly through an intrusive growth of cell ends from one radial file entering space between tangential walls of neighboring file and through unequal periclinal divisions that occur in the "initial surface". The intrusive growth is located on the longitudinal edge of a fusiform cell close to the end, and causes deviation of cell ends in a neighbouring file from the initial surface. Unequal periclinal division divides a cell with a deviated end into two derivatives, unequal in size. The one of them, which inherits the deviated end, leaves the initial surface becoming a xylem or phloem mother cell. This means that the old end is eliminated. The intensity of intrusive growth and unequal periclinal divisions is decisive for the velocity of cambial cell reorientation. The oriented intrusive growth occurs only in the initial cells. For that reason, changes in cell-ends position do not occur within one packet of cells but are distinct between neighbouring packets.

  5. DNA replication initiation, doubling of rate of phospholipid synthesis, and cell division in Escherichia coli.

    OpenAIRE

    Joseleau-Petit, D; Képès, F; Peutat, L; D'Ari, R; Képès, A

    1987-01-01

    In synchronized culture of Escherichia coli, the specific arrest of phospholipid synthesis (brought about by glycerol starvation in an appropriate mutant) did not affect the rate of ongoing DNA synthesis but prevented the initiation of new rounds. The initiation block did not depend on cell age at the time of glycerol removal, which could be before, during, or after the doubling in the rate of phospholipid synthesis (DROPS) and as little as 10 min before the expected initiation. We conclude t...

  6. Acetate is a superior substrate for microbial fuel cell initiation preceding bioethanol effluent utilization

    DEFF Research Database (Denmark)

    Sun, Guotao; Thygesen, Anders; Meyer, Anne S.

    2015-01-01

    resistance. The BE mainly contained 20.5 g/L xylose, 1.8 g/Larabinose, and 2.5 g/L propionic acid. The MFCs initially fedwith acetate showed shorter initiation time (1 day), higheraverage cell voltage (634±9 mV), and higher coulombic efficiency(31.5±0.5 %) than those initially fed with ace/xyl orxylose...

  7. Initiation and characterization of a glioblastoma multiforme derived cell line.

    Directory of Open Access Journals (Sweden)

    Carmen Lucía Roa

    2009-11-01

    Full Text Available Introducción: Las líneas celulares y los cultivos primarios son una excelente herramienta para el estudio de la biología, desarrollo y respuesta a la terapia en tumores cerebrales. Objetivo: Establecer y caracterizar una línea celular derivada de un glioblastoma multiforme como un modelo de estudio in vitro para la extrapolación y aplicación futura en terapia génica. Material y métodos: Se obtuvo una muestra de un paciente con diagnóstico clínico e histopatológico de glioblastoma multiforme, se caracterizó mediante inmunohistoquímica en cortes de tejido y por inmunocitoquímica sobre células cultivadas a partir del tumor desde el inicio del cultivo y durante los seis primeros pases, con dos tipos de marcadores específicos para glía: GFAP (glial fibrillary acidic protein y S-100 (proteína de unión a calcio. Además, se evaluó la expresión de p53 y Bcl-2, como moduladores de apoptosis. Por último se hizo la caracterización citogenética. Resultados: Histopatológicamente, se confirmó el diagnóstico de glioblastoma multiforme. En los cultivos primarios se encontraron características citomorfológicas propias de un glioblastoma: células fibroblastoides planas, células con escaso citoplasma con 3 ó más procesos y por último bipolares o unipolares. Se encontró una expresión diferencial con los cuatro marcadores, con un patrón de marcaciones a nivel citoplasmático y nuclear a través de los pases estudiados. La línea celular se caracterizó por ser en su mayoría aneuploide con un número modal cromosómico entre 43 y 45, con un gran número de poliploidías (55-102 , XXYY y endo-reduplicaciones (end 45, X, -Y. Conclusión: Se estableció una línea celular derivada de un glioblastoma multiforme con un fenotipo estable, con un notable mantenimiento del perfil glial y citogenético.

  8. Cell surface galectin-3 defines a subset of chemoresistant gastrointestinal tumor-initiating cancer cells with heightened stem cell characteristics.

    Science.gov (United States)

    Ilmer, Matthias; Mazurek, Nachman; Byrd, James C; Ramirez, Karen; Hafley, Margarete; Alt, Eckhard; Vykoukal, Jody; Bresalier, Robert S

    2016-01-01

    Recurrence of gastrointestinal adenocarcinomas after surgery and chemotherapy may be attributed, in part, to the presence of a small population of tumor-initiating cancer stem cells (CSC). The expression of galectin-3 (Gal3), a multifunctional oncolectin, has been associated with biological behaviors associated with CSC. We examined the ability of Gal3 to characterize the CSC phenotype, and to identify a clinically important gastrointestinal cancer CSC population. Human colorectal and pancreatic cancer cell lines were sorted to identify subpopulations expressing commonly used CSC markers, and Gal3-positive CSC subpopulations. The association of Gal3 with the stem cell properties and alterations of these phenotypes by manipulation of Gal3 expression was examined. Gastrointestinal cancer cell lines contain both Gal3-positive and Gal3-negative subpopulations. Gal3-positive CSCs are characterized by high ALDH activity, enhanced self-renewal ability in vitro (sphere formation) and tumor forming ability in vivo, and resistance to chemotherapeutic agents and death-receptor-mediated apoptosis compared to Gal3-negative CSCs. Silencing Gal3 modifies this behavior. Cell surface Gal3 expression identifies a subset of CSCs in gastrointestinal cancers with high levels of stem cell characteristics, including chemoresistance. This may provide a platform for developing treatment strategies that target CSC. PMID:27512958

  9. Identification and analysis of CXCR4-positive synovial sarcoma-initiating cells.

    Science.gov (United States)

    Kimura, T; Wang, L; Tabu, K; Tsuda, M; Tanino, M; Maekawa, A; Nishihara, H; Hiraga, H; Taga, T; Oda, Y; Tanaka, S

    2016-07-28

    Synovial sarcoma accounts for almost 10% of all soft tissue sarcomas, and its prognosis is poor with 5-year survival rates at 36%. Thus, new treatments and therapeutic targets for synovial sarcoma are required. Tumor-initiating cells have been defined by the ability for self-renewal and multipotent differentiation, and they exhibit higher tumorigenic capacity, chemoresistance and radiation resistance, expecting to be a new therapeutic target. In synovial sarcoma, the presence of such stemness remains largely unclear; thus, we analyzed whether synovial sarcoma possessed tumor-initiating cells and explored specific markers, and we discovered that synovial sarcoma cell lines possessed heterogeneity by way of containing a sphere-forming subpopulation highly expressing NANOG, OCT4 and SOX2. By expression microarray analysis, CXCR4 was identified to be highly expressed in the sphere subpopulation and correlated with stem-cell-associated markers. Inhibition of CXCR4 suppressed the cell proliferation of synovial sarcoma cell lines in vitro. The tumor-initiating ability of CXCR4-positive cells was demonstrated by xenograft propagation assay. CXCR4-positive cells showed higher tumorigenicity than negative ones and possessed both self-renewal and multipotent differentiation ability. Immunohistochemical analysis of 39 specimens of synovial sarcoma patients revealed that CXCR4 strongly correlated with poor prognosis of synovial sarcoma. Thus, we conclude that CXCR4 is the marker of synovial sarcoma-initiating cells, a new biomarker for prognosis and a new potential therapeutic target. PMID:26640147

  10. Notch signalling inhibits CD4 expression during initiation and differentiation of human T cell lineage.

    Directory of Open Access Journals (Sweden)

    Stephen M Carlin

    Full Text Available The Delta/Notch signal transduction pathway is central to T cell differentiation from haemopoietic stem cells (HSCs. Although T cell development is well characterized using expression of cell surface markers, the detailed mechanisms driving differentiation have not been established. This issue becomes central with observations that adult HSCs exhibit poor differentiation towards the T cell lineage relative to neonatal or embryonic precursors. This study investigates the contribution of Notch signalling and stromal support cells to differentiation of adult and Cord Blood (CB human HSCs, using the Notch signalling OP9Delta co-culture system. Co-cultured cells were assayed at weekly intervals during development for phenotype markers using flow cytometry. Cells were also assayed for mRNA expression at critical developmental stages. Expression of the central thymocyte marker CD4 was initiated independently of Notch signalling, while cells grown with Notch signalling had reduced expression of CD4 mRNA and protein. Interruption of Notch signalling in partially differentiated cells increased CD4 mRNA and protein expression, and promoted differentiation to CD4(+ CD8(+ T cells. We identified a set of genes related to T cell development that were initiated by Notch signalling, and also a set of genes subsequently altered by Notch signal interruption. These results demonstrate that while Notch signalling is essential for establishment of the T cell lineage, at later stages of differentiation, its removal late in differentiation promotes more efficient DP cell generation. Notch signalling adds to signals provided by stromal cells to allow HSCs to differentiate to T cells via initiation of transcription factors such as HES1, GATA3 and TCF7. We also identify gene expression profile differences that may account for low generation of T cells from adult HSCs.

  11. Alveolar type II cells possess the capability of initiating lung tumor development.

    Directory of Open Access Journals (Sweden)

    Chuwen Lin

    Full Text Available Identifying cells of tumor origin is a fundamental question in tumor biology. Answers to this central question will not only advance our understanding of tumor initiation and progression but also have important therapeutic implications. In this study, we aimed to uncover the cells of origin of lung adenocarcinoma, a major subtype of non-small cell lung cancer. To this end, we developed new mouse models of lung adenocarcinoma that enabled selective manipulation of gene activity in surfactant associated protein C (SPC-expressing cells, including alveolar type II cells and bronchioalveolar stem cells (BASCs that reside at the bronchioalveolar duct junction (BADJ. Our findings showed that activation of oncogenic Kras alone or in combination with the removal of the tumor suppressor p53 in SPC⁺ cells resulted in development of alveolar tumors. Similarly, sustained EGF signaling in SPC⁺ cells led to alveolar tumors. By contrast, BASCs failed to proliferate or produce tumors under these conditions. Importantly, in a mouse strain in which Kras/p53 activity was selectively altered in type II cells but not BASCs, alveolar tumors developed while BADJs retained normal architecture. These results confirm and extend previous findings and support a model in which lung adenocarcinoma can initiate in alveolar type II cells. Our results establish the foundation for elucidating the molecular mechanisms by which lung cancer initiates and progresses in a specific lung cell type.

  12. The Development of the Manchester Motor Skills Assessment (MMSA): An Initial Evaluation

    Science.gov (United States)

    Bond, C.; Cole, M.; Crook, H.; Fletcher, J.; Lucanz, J.; Noble, J.

    2007-01-01

    This article is an initial evaluation of a motor skills assessment for primary aged children. The Manchester Motor Skills Assessment (MMSA) is designed to be quick and easy for teaching assistants to complete, with the dual purposes of informing group programme planning and demonstrating an individual child's progress following a period of…

  13. Housing Services for Child Welfare-Involved Families: An Initial Evaluation Using Observational Data

    Science.gov (United States)

    Fowler, Patrick J.; Taylor, Jeremy J.; Rufa, Anne K.

    2011-01-01

    This study evaluated the impact of housing services among child welfare-involved families using observational data. Propensity score matching with data from the National Survey of Child and Adolescent Well-Being compared intact families (n = 183) who received housing services 12 months after initial investigation to nontreated families balanced on…

  14. Evaluating Voluntary Climate Change Initiatives by US business and industry compared with the Dutch experience

    NARCIS (Netherlands)

    Dave R; Elzenga HE; Moor APG de; KMD

    2005-01-01

    This report evaluates voluntary climate change initiatives by US business and industry geared to reducing greenhouse gases. We conclude that most of them do not even meet the minimum requirements to be qualified as serious efforts. They lack sufficient information, ambition and direction. Targets ar

  15. Social capital, agricultural innovation and the evaluation of agricultural development initiatives

    NARCIS (Netherlands)

    Rijn, van F.C.

    2014-01-01

    In this thesis, I show that social capital has an important role in the evaluation of development initiatives targeting agricultural innovation. Social capital and agricultural innovation are naturally linked from an innovation system perspective in which innovations result from the integration of k

  16. Using the Concept of "Population Dose" in Planning and Evaluating Community-Level Obesity Prevention Initiatives

    Science.gov (United States)

    Cheadle, Allen; Schwartz, Pamela M.; Rauzon, Suzanne; Bourcier, Emily; Senter, Sandra; Spring, Rebecca; Beery, William L.

    2013-01-01

    When planning and evaluating community-level initiatives focused on policy and environment change, it is useful to have estimates of the impact on behavioral outcomes of particular strategies (e.g., building a new walking trail to promote physical activity). We have created a measure of estimated strategy-level impact--"population dose"--based on…

  17. Qualitative evaluation of interprofessional learning initiatives in practice: application of the contact hypothesis

    Directory of Open Access Journals (Sweden)

    Penny J. Furness

    2012-04-01

    Full Text Available Objectives: The evaluation aimed to explore reactions to, learning from and the perceived impact and sustainability of practice-based interprofessional learning initiatives established by The Trent Universities Interprofessional Learning in Practice project. Methods: The evaluation had a qualitative design and was guided by Kirkpatrick's evaluation framework. Facilitators, managers, practitioners, students and service users were invited to participate. This article focuses upon three of the project's practice-based interprofessional initiatives. Fifteen participants were interviewed about their experiences of, and opinions about, the initiative in their practice setting. A thematic analysis was conducted, following which findings were considered through the lens of the 'contact hypothesis' a theoretical framework which sets out variables purported to influence the success of inter-group contact. Results: Seven themes were identified. Four derived from Kirkpatrick's framework: reaction, learning, impact and sustainability. Initial reactions were positive; however learning and impact were considered minimal, and sustainability unlikely. The evaluation revealed significant problems in developing successful, sustainable, service user-focused interprofessional learning opportunities in these three sites. Three final themes were based upon contact hypothesis variables which helped elucidate the disappointing outcomes: organisational support, positive expectations, and co-operation/working together. Conclusions: Results offer insights which could help medical education establishments and their practice partners develop successful practice-based interprofessional learning initiatives for students in the future. Initiatives should be designed to meet local working practices and opportunities; there should be an awareness that change is challenging and time-consuming; and preparation of and support in host organisations at all levels should be a priority.

  18. Factorial Validity of a Questionnaire to Evaluate University Students' Initial Perception of Learning Evaluation

    Science.gov (United States)

    Doménech-Betoret, Fernando; Fortea-Bagán, Miguel Angel

    2015-01-01

    Introduction: Education research has clearly verified that a student's perception of the system to evaluate the subject matter will play a fundamental role in his/her implication (deep approach vs. surface approach) in the teaching/learning process of the subject matter. The present work aims to examine the factorial validity and reliability of a…

  19. Evaluating financial education initiatives in South Africa: The importance of multiple evaluation approaches

    Directory of Open Access Journals (Sweden)

    Emily Massey

    2016-06-01

    Full Text Available Background: Given the low levels of financial literacy in South Africa, financial education projects have a significant role to play in reducing some of the demand side barriers to financial inclusion. Measuring the impact of a financial education project is important to assess whether the project achieves its ultimate objectives, for justifying scaling up and for policy design. However, impact evaluations alone are not sufficient in describing the success or failure of a project.Objectives: This study aims to show that, particularly in a South African context, where investment in financial education interventions is mandated by the Financial Sector Codes, impact should not be the only criterion assessed when evaluating financial education projects.Research method and design: This study was informed by a literature review, a synthesis of team experience on a range of financial education projects in South Africa and the development of case studies.Results: Describing the success or failure of a project needs to go beyond impact and explore factors such as project relevance, design and quality. In order to verify these other factors, different types of evaluations are necessary at the various stages of the project’s life-cycle.Conclusion: Expanding the learning objective beyond the exclusive identification of whether financial behaviour was achieved is particularly important where financial education projects, and the monitoring and evaluation thereof, is mandated. In the African context, where resources are scarce, money for monitoring and evaluation should be selectively channelled into determining project relevance, effectiveness, efficiency and then only impact.

  20. Preliminary analysis of cellular sociology of co-cultured glioma initiating cells and macrophages in vitro

    Institute of Scientific and Technical Information of China (English)

    Mingxia Zhang; Xingliang Dai; Xiaonan Li; Qiang Huang; Jun Dong; Junjie Chen; Lin Wang; Xiaoyan Ji; Lin Yang; Yujing Sheng; Hairui Liu; Haiyang Wang; Aidong Wang

    2016-01-01

    Objective:Real-time monitoring of cytokine secretion at the single immunocyte level, based on the concept of immune cells, sociology has been recently reported. However, the relationships between glioma-initiating cells (GICs) and host immune cells and their mutual interactions in the tumor microenvironment have not been directly observed and remain unclear. Methods:The dual fluorescence tracing technique was applied to label the co-cultured GICs and host macrophages (Mø), and the interactions between the two types of cells were observed using a live cell imaging system. Fusion cells in the co-culture system were monocloned and proliferated in vitro and their social interactions were observed and recorded. Results:Using real-time dynamic observation of target cells, 6 types of intercellular conjunction microtubes were found to function in the transfer of intercellular information between GICs and Mø;GICs and host Mø can fuse into hybrid cells after several rounds of mutual interactions, and then these fusion cells fused with each other;Fusion cells generated offspring cells through symmetrical and asymmetrical division or underwent apoptosis. A“cell in cell” phenomenon was observed in the fusion cells, which was often followed by cell release, namely entosis. Conclusions:Preliminary studies revealed the patterns of cell conjunction via microtubes between GICs and host Mø and the processes of cell fusion, division, and entosis. The results revealed malignant transformation of host Mø, induced by GICs, suggesting complex social relationships among tumor-immune cells in gliomas.

  1. Pulmonary Embolism as the Initial Manifestation of Large Cell Lung Cancer

    OpenAIRE

    Kim, Jin Kook; Lee, Sang Moo; Kim, Hyeon Tae; Uh, Sootaek; Chung, Yeontae; Kim, Yong Hoon; Park, Choonsik; Jin, So Young; Lee, Dong Hwa

    1992-01-01

    Lung cancer is known as a risk factor of pulmonary embolism. We experienced a case of pulmonary embolism combined with pleural effusion and pleuritic chest pain as the initial manifestation of large cell lung cancer, which is a relatively rare cell type of lung cancer in Korea. We report it with a review of the literature.

  2. Evaluating financial education initiatives in South Africa: The importance of multiple evaluation approaches

    OpenAIRE

    Emily Massey; Alyna Wyatt; Caitlin Smit

    2016-01-01

    Background: Given the low levels of financial literacy in South Africa, financial education projects have a significant role to play in reducing some of the demand side barriers to financial inclusion. Measuring the impact of a financial education project is important to assess whether the project achieves its ultimate objectives, for justifying scaling up and for policy design. However, impact evaluations alone are not sufficient in describing the success or failure of a project.Objectives: ...

  3. The Evaluation of the Initial Shear Modulus of Selected Cohesive Soils

    Directory of Open Access Journals (Sweden)

    Gabryś Katarzyna

    2015-06-01

    Full Text Available The paper concerns the evaluation of the initial stiffness of selected cohesive soils based on laboratory tests. The research materials used in this study were clayey soils taken from the area of the road embankment No. WD-18, on the 464th km of the S2 express-way, Konotopa-Airport route, Warsaw. The initial stiffness is represented here by the shear modulus (Gmax determined during resonant column tests. In the article, a number of literature empirical formulas for defining initial value of the shear modulus of soils being examined were adopted from the literature in order to analyze the data set. However, a large discrepancy between laboratory test results and the values of Gmax calculated from empirical relationships resulted in the rejection of these proposals. They are inaccurate and do not allow for an exact evaluation of soil stiffness for selected cohesive soils. Hence, the authors proposed their own empirical formula that enables the evaluation of the test soils’ Gmax in an easy and uncomplicated way. This unique formula describes mathematically the effect of certain soil parameters, namely mean effective stress ( p′ and void ratio (e, on the initial soil stiffness.

  4. A longitudinal evaluation of a project-based learning initiative in an engineering undergraduate programme

    Science.gov (United States)

    Hall, Wayne; Palmer, Stuart; Bennett, Mitchell

    2012-05-01

    Project-based learning (PBL) is a well-known student-centred methodology for engineering design education. The methodology claims to offer a number of educational benefits. This paper evaluates the student perceptions of the initial and second offering of a first-year design unit at Griffith University in Australia. It builds on an earlier evaluation conducted after the initial offering of the unit. It considers the implementation of the recommended changes. Evaluations of the two offerings reveal that students (in both the initial and second offering) generally enjoyed the experience, but that the second offering was found to be a significantly more enjoyable learning experience. Students in the second offering also reported a significantly better understanding of what they needed to do for the design projects and where to find the requisite information. The oral presentation aspect of the initial and second offerings received the lowest satisfaction rating. The inclusion (and delivery) of the computer-aided drawing component of the unit is seen as a positive aspect by some students, but many others comment on it negatively. The best aspects of the PBL unit and those aspects needing further improvement were similar to the findings of other investigations documented in the literature.

  5. Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Na [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114 (United States); Chen, Yan [Central Laboratory, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Wang, Zhengmin [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Institute of Biomedical Sciences, Fudan University, Shanghai 200032 (China); Chen, Guoling [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Lin, Qin [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Department of Otolaryngology, First Affiliated Hospital of Fujian Medical University, Otolaryngology Institute of Fujian Province, Fuzhou (China); Chen, Zheng-Yi, E-mail: Zheng-yi_chen@meei.harvard.edu [Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114 (United States); Li, Huawei, E-mail: hwli@shmu.edu.cn [Otology Skull Base Surgery Department, Hearing Research Institute, Eye and ENT Hospital of Shanghai Medical School, Fudan University, Shanghai 200031 (China); Institute of Biomedical Sciences, Fudan University, Shanghai 200032 (China)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer Shh activation in neonatal cochleae enhances sensory cell proliferation. Black-Right-Pointing-Pointer Proliferating supporting cells can transdifferentiate into hair cells. Black-Right-Pointing-Pointer Shh promotes proliferation by transiently modulating pRb activity. Black-Right-Pointing-Pointer Shh inhibits pRb by inhibiting transcription and increasing phosphorylation of pRb. -- Abstract: Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration.

  6. Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein

    International Nuclear Information System (INIS)

    Highlights: ► Shh activation in neonatal cochleae enhances sensory cell proliferation. ► Proliferating supporting cells can transdifferentiate into hair cells. ► Shh promotes proliferation by transiently modulating pRb activity. ► Shh inhibits pRb by inhibiting transcription and increasing phosphorylation of pRb. -- Abstract: Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration.

  7. Role of tumour initiating cells in the radiation resistance of osteosarcoma

    International Nuclear Information System (INIS)

    In the present study we confirm that mouse osteosarcoma (MOS) cells lines possess a subset of cells with Tumour Initiating Cells (TICs) properties. We found that isolated TICs are not inherently radioresistant compared to non-TICs. On the other hand, we found that the fraction of TICs correlates well with the radiosensitivity of MOS cell lines measured using clonogenic cell survival assay. We conclude from our study that the TICs contribute to the tumour radiation response due to their interaction with their tumour surrounding environmental (niche).

  8. Microtubule cytoskeleton behavior in the initial steps of host cell invasion by Besnoitia besnoiti

    OpenAIRE

    REIS, Y; CORTES, H; VISEUMELO, L; FAZENDEIRO, I; Leitao, A.; SOARES, H

    2006-01-01

    Microtubule cytoskeleton behavior in the initial steps of host cell invasion by Besnoitia besnoiti Besnoitia besnoiti is a protozoan parasite responsible for bovine besnoitiosis. Indirect immunofluorescence showed that isolated B. besnoiti possesses a set of subpellicular microtubules, radiating from the apical end and extending for more than 2/3 of the cell body. Upon interaction with the host cell, B. besnoiti undergoes dramatic modifications of shape and surface, as revealed by atomic ...

  9. Maintenance of leukemia-initiating cells is regulated by the CDK inhibitor Inca1.

    Directory of Open Access Journals (Sweden)

    Nicole Bäumer

    Full Text Available Functional differences between healthy progenitor and cancer initiating cells may provide unique opportunities for targeted therapy approaches. Hematopoietic stem cells are tightly controlled by a network of CDK inhibitors that govern proliferation and prevent stem cell exhaustion. Loss of Inca1 led to an increased number of short-term hematopoietic stem cells in older mice, but Inca1 seems largely dispensable for normal hematopoiesis. On the other hand, Inca1-deficiency enhanced cell cycling upon cytotoxic stress and accelerated bone marrow exhaustion. Moreover, AML1-ETO9a-induced proliferation was not sustained in Inca1-deficient cells in vivo. As a consequence, leukemia induction and leukemia maintenance were severely impaired in Inca1-/- bone marrow cells. The re-initiation of leukemia was also significantly inhibited in absence of Inca1-/- in MLL-AF9- and c-myc/BCL2-positive leukemia mouse models. These findings indicate distinct functional properties of Inca1 in normal hematopoietic cells compared to leukemia initiating cells. Such functional differences might be used to design specific therapy approaches in leukemia.

  10. Role of Fbxw7 in the maintenance of normal stem cells and cancer-initiating cells

    OpenAIRE

    Takeishi, S; Nakayama, K I

    2014-01-01

    In addition to the properties of self-renewal and multipotency, stem cells are characterised by their distinct cell cycle status. Somatic stem cells are maintained in a quiescent state but switch reversibly from quiescence to proliferation as needed. On the other hand, embryonic stem cells and induced pluripotent stem cells proliferate rapidly until the induction of differentiation results in inhibition of cell cycle progression. Uncovering the mechanisms underlying cell cycle control in stem...

  11. Gossypol induces apoptosis by activating p53 in prostate cancer cells and prostate tumor-initiating cells

    OpenAIRE

    Volate, Suresh R.; Kawasaki, Brian T.; Hurt, Elaine M.; Milner, John A.; Kim, Young S.; White, Jeffrey; Farrar, William L.

    2010-01-01

    Prostate cancer (PCa) continues to represent a burgeoning medical problem in the United States. Recent studies suggest that gossypol, a bioactive phytochemical produced by cotton plants, is a promising agent against prostate cancer. The current studies were undertaken to examine the chemotherapeutic efficacy of gossypol on human prostate cancer cell lines and prostate tumor-initiating cells (pTICs). Gossypol reduced viability of three prostate cancer cell lines (LAPC4, PC3, and DU145) with an...

  12. Evaluating nuclear power: voter choice on the California nuclear energy initiative. Executive summary

    International Nuclear Information System (INIS)

    In 1976, under grants from the National Science Foundation and the Ford Foundation, The Rand Corporation conducted a set of surveys of Californians' attitudes toward nuclear power nd Proposition 15 that we hoped would illuminate the reasons for the voters' decision on the nuclear initiative. The study focused on the attitudes of the general public; it did not investigate the factors that motivate activists on both sides of the nuclear controversy. The study was limited to California, but because results indicate that attitudes of Californians are similar to attitudes reported in nationwide surveys, we believe that our findings have broader applicability. The objectives of the study were to: describe public knowledge, beliefs, and evaluation of nuclear energy development; analyze the relationship between beliefs and evaluation of nuclear energy; investigate the relationship between critical beliefs about nuclear energy and general political orientations, trust in government and other political and social institutions, and social background characteristics; describe public knowledge, beliefs, and evaluation of Proposition 15, the California nuclear energy initiative; and investigate the relationship between individuals' voting decisions on Proposition 15 and their evaluations of nuclear power and responses to the initiative campaign

  13. Successful Reconstruction of Tooth Germ with Cell Lines Requires Coordinated Gene Expressions from the Initiation Stage

    Directory of Open Access Journals (Sweden)

    Yasuhiro Tomooka

    2012-10-01

    Full Text Available Tooth morphogenesis is carried out by a series of reciprocal interactions between the epithelium and mesenchyme in embryonic germs. Previously clonal dental epithelial cell (epithelium of molar tooth germ (emtg lines were established from an embryonic germ. They were odontogenic when combined with a dental mesenchymal tissue, although the odontogenesis was quantitatively imperfect. To improve the microenvironment in the germs, freshly isolated dental epithelial cells were mixed with cells of lines, and germs were reconstructed in various combinations. The results demonstrated that successful tooth construction depends on the mixing ratio, the age of dental epithelial cells and the combination with cell lines. Analyses of gene expression in these germs suggest that some signal(s from dental epithelial cells makes emtg cells competent to communicate with mesenchymal cells and the epithelial and mesenchymal compartments are able to progress  odontogenesis from the initiation stage.

  14. Evaluation of osteogenic cell culture and osteogenic/peripheral blood mononuclear human cell co-culture on modified titanium surfaces

    International Nuclear Information System (INIS)

    This study aimed to determine the effect of a bioactive ceramic coating on titanium in the nanothickness range on human osteogenic cells, peripheral blood mononuclear cells (PBMC) and on osteogenic cells co-cultured with PBMC without exogenous stimuli. Cell viability, proliferation, adhesion, cytokine release (IL1β, TGFβ1, IL10 and IL17) and intracellular stain for osteopontin and alkaline phosphatase were assessed. Morphologic evaluation showed smaller and less spread cell aspects in co-culture relative to osteogenic cell culture. Cell viability, proliferation and adhesion kinetics were differently influenced by surface texture/chemistry in culture versus co-culture. Cytokine release was also influenced by the interaction between mononuclear and osteogenic cells (mediators released by mononuclear cells acted on osteogenic cells and vice versa). In general, ‘multi-cell type’ interactions played a more remarkable role than the surface roughness or chemistry utilized on the in vitro cellular events related to initial stages of bone formation. (paper)

  15. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    International Nuclear Information System (INIS)

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy

  16. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo-Shin; Lee, Tae Hoon; O' Neill, Brian E., E-mail: BEOneill@houstonmethodist.org

    2015-08-14

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

  17. An inhibitor of K+ channels modulates human endometrial tumor-initiating cells

    Directory of Open Access Journals (Sweden)

    Leslie Kimberly K

    2011-08-01

    Full Text Available Abstract Background Many potassium ion (K+ channels function as oncogenes to sustain growth of solid tumors, but their role in cancer progression is not well understood. Emerging evidence suggests that the early progenitor cancer cell subpopulation, termed tumor initiating cells (TIC, are critical to cancer progression. Results A non-selective antagonist of multiple types of K+ channels, tetraethylammonium (TEA, was found to suppress colony formation in endometrial cancer cells via inhibition of putative TIC. The data also indicated that withdrawal of TEA results in a significant enhancement of tumorigenesis. When the TIC-enriched subpopulation was isolated from the endometrial cancer cells, TEA was also found to inhibit growth in vitro. Conclusions These studies suggest that the activity of potassium channels significantly contributes to the progression of endometrial tumors, and the antagonists of potassium channels are candidate anti-cancer drugs to specifically target tumor initiating cells in endometrial cancer therapy.

  18. Evaluation of crevice corrosion initiation condition and repassivation condition of SUS304L

    International Nuclear Information System (INIS)

    Crevice corrosion has been concerned in the Fukushima Daiichi Nuclear Power Station, since seawater was injected to make up water level as part of the emergency action. To evaluate structural integrity, it is important to investigate whether crevice corrosion occurred. The purpose of this study is to investigate conditions of crevice corrosion initiation and repassivation of SUS304L. SUS304L specimens with acrylic crevice were held at constant electrochemical potentials in 1000ppm Cl- solution. It was investigated the crevice corrosion initiation time as a function of the holding potential. Next, crevice-corroding specimens were held at constant electrochemical potentials in 1000ppm Cl- solution. It was investigated the repassivation time against the holding potential. The initiation potential and repassivation potential are in good agreement with ER,CREV obtained according to the JIS standard. (author)

  19. Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity.

    Directory of Open Access Journals (Sweden)

    Ganapati V Hegde

    Full Text Available Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs. We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell's ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell's ability to drive disease recurrence.

  20. Apoptotic cells trigger a membrane-initiated pathway to increase ABCA1.

    Science.gov (United States)

    Fond, Aaron M; Lee, Chang Sup; Schulman, Ira G; Kiss, Robert S; Ravichandran, Kodi S

    2015-07-01

    Macrophages clear millions of apoptotic cells daily and, during this process, take up large quantities of cholesterol. The membrane transporter ABCA1 is a key player in cholesterol efflux from macrophages and has been shown via human genetic studies to provide protection against cardiovascular disease. How the apoptotic cell clearance process is linked to macrophage ABCA1 expression is not known. Here, we identified a plasma membrane-initiated signaling pathway that drives a rapid upregulation of ABCA1 mRNA and protein. This pathway involves the phagocytic receptor brain-specific angiogenesis inhibitor 1 (BAI1), which recognizes phosphatidylserine on apoptotic cells, and the intracellular signaling intermediates engulfment cell motility 1 (ELMO1) and Rac1, as ABCA1 induction was attenuated in primary macrophages from mice lacking these molecules. Moreover, this apoptotic cell-initiated pathway functioned independently of the liver X receptor (LXR) sterol-sensing machinery that is known to regulate ABCA1 expression and cholesterol efflux. When placed on a high-fat diet, mice lacking BAI1 had increased numbers of apoptotic cells in their aortic roots, which correlated with altered lipid profiles. In contrast, macrophages from engineered mice with transgenic BAI1 overexpression showed greater ABCA1 induction in response to apoptotic cells compared with those from control animals. Collectively, these data identify a membrane-initiated pathway that is triggered by apoptotic cells to enhance ABCA1 within engulfing phagocytes and with functional consequences in vivo. PMID:26075824

  1. The Hemopoietic Stem Cell Niche Versus the Microenvironment of the Multiple Myeloma-Tumor Initiating Cell

    OpenAIRE

    Zipori, Dov

    2010-01-01

    Multiple myeloma cells are reminiscent of hemopoietic stem cells in their strict dependence upon the bone marrow microenvironment. However, from all other points of view, multiple myeloma cells differ markedly from stem cells. The cells possess a mature phenotype and secrete antibodies, and have thus made the whole journey to maturity, while maintaining a tumor phenotype. Not much credence was given to the possibility that the bulk of plasma-like multiple myeloma tumor cells is generated from...

  2. Assessing Patients’ Cognitive Therapy Skills: Initial Evaluation of the Competencies of Cognitive Therapy Scale

    Science.gov (United States)

    Strunk, Daniel R.; Hollars, Shannon N.; Adler, Abby D.; Goldstein, Lizabeth A.; Braun, Justin D.

    2014-01-01

    In Cognitive Therapy (CT), therapists work to help patients develop skills to cope with negative affect. Most current methods of assessing patients’ skills are cumbersome and impractical for clinical use. To address this issue, we developed and conducted an initial psychometric evaluation of self and therapist reported versions of a new measure of CT skills: the Competencies of Cognitive Therapy Scale (CCTS). We evaluated the CCTS at intake and post-treatment in a sample of 67 patients participating in CT. The CCTS correlated with a preexisting measure of CT skills (the Ways of Responding Questionnaire) and was also related to concurrent depressive symptoms. Across CT, self-reported improvements in CT competencies were associated with greater changes in depressive symptoms. These findings offer initial evidence for the validity of the CCTS. We discuss the CCTS in comparison with other measures of CT skills and suggest future research directions. PMID:25408560

  3. Using photovoice as a participatory evaluation tool in Kaiser Permanente's Community Health Initiative.

    Science.gov (United States)

    Kramer, Leila; Schwartz, Pamela; Cheadle, Allen; Rauzon, Suzanne

    2013-09-01

    Photovoice is a community-based participatory research method that provides participants who traditionally have little voice in community policy decisions, with training in photography, ethics, critical dialogue, photo captioning, and policy advocacy. Photovoice has been used primarily as a needs assessment and advocacy tool and only rarely as a pre-/postintervention evaluation method. This article describes the use of Photovoice as a participatory evaluation method in the Community Health Initiative, a 6-year, multisite community-based obesity prevention initiative, sponsored by Kaiser Permanente. Fifty community participants (including six youth) from six Community Health Initiative communities used photos and captions to identify, from their perspective, the most significant accomplishments from the initiative at both baseline and follow-up. Accomplishments identified included increased access to fresh/healthy food in local neighborhoods; policy changes supporting a "healthy eating, active living" community; increased access to physical activity; changes to the built environment creating increased neighborhood walkability/safety; and leadership development. PMID:23159999

  4. Evaluation of a cross-sector community initiative partnership: delivering a local sport program.

    Science.gov (United States)

    Kihl, Lisa A; Tainsky, Scott; Babiak, Kathy; Bang, Hyejin

    2014-06-01

    Corporate community initiatives (CCI) are often established via cross-sector partnerships with nonprofit agencies to address critical social problems. While there is a growing body of literature exploring the effectiveness and social impact of these partnerships, there is a limited evaluative research on the implementation and execution processes of CCIs. In this paper, we examined the implementation and operational processes in the delivery of a professional sport organization's CCI initiative using program theory evaluation. The findings showed discrepancies between the associate organization and the implementers regarding understanding and fulfilling responsibilities with performing certain aspects (maintaining accurate records and program marketing) of the service delivery protocol. Despite program stakeholders being satisfied overall with the program delivery, contradictions between program stakeholders' satisfaction in the quality of program delivery was found in critical components (marketing and communications) of the service delivery. We conclude that ongoing evaluations are necessary to pinpoint the catalyst of the discrepancies along with all partners valuing process evaluation in addition to outcome evaluation. PMID:24530863

  5. KiwiSaver: An Initial Evaluation of the Impact on Retirement Saving

    OpenAIRE

    David Law; Lisa Meehan; Scobie, Grant M.

    2011-01-01

    KiwiSaver is a voluntary savings scheme aimed at increasing the retirement wealth of a target population. A critical element shaping the success of KiwiSaver is the extent to which individuals participate in the scheme, given its voluntary nature; and, having chosen to participate, the extent to which their attitudes and practices toward savings have been modified by their participation. This paper presents the results of an initial evaluation to assess individuals' saving behaviour following...

  6. Climate Policy and Voluntary Initiatives: An Evaluation of the Connecticut Clean Energy Communities Program

    OpenAIRE

    Matthew J. Kotchen

    2010-01-01

    Can simple government programs effectively promote voluntary initiatives to reduce greenhouse-gas emissions? This paper provides an evaluation of how the Connecticut Clean Energy Communities program affects household decisions to voluntarily purchase "green" electricity, which is electricity generated from renewable sources of energy. The results suggest that, within participating communities, subsidizing municipal solar panels as matching grants for reaching green-electricity enrollment targ...

  7. Stereotyped initiation of retinal waves by bipolar cells via presynaptic NMDA autoreceptors.

    Science.gov (United States)

    Zhang, Rong-Wei; Li, Xiao-Quan; Kawakami, Koichi; Du, Jiu-Lin

    2016-01-01

    Glutamatergic retinal waves, the spontaneous patterned neural activities propagating among developing retinal ganglion cells (RGCs), instruct the activity-dependent refinement of visuotopic maps. However, its initiation and underlying mechanism remain largely elusive. Here using larval zebrafish and multiple in vivo approaches, we discover that bipolar cells (BCs) are responsible for the generation of glutamatergic retinal waves. The wave originates from BC axon terminals (ATs) and propagates laterally to nearby BCs and vertically to downstream RGCs and the optic tectum. Its initiation is triggered by the activation of and consequent glutamate release from BC ATs, and is mediated by the N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) expressed at these ATs. Intercellular asymmetry of NMDAR expression at BC ATs enables the preferential initiation of waves at the temporal retina, where BC ATs express more NMDARs. Thus, our findings indicate that glutamatergic retinal waves are initiated by BCs through a presynaptic NMDA autoreceptor-dependent process. PMID:27586999

  8. Tumor-initiating cells are enriched in CD44(hi population in murine salivary gland tumor.

    Directory of Open Access Journals (Sweden)

    Shukun Shen

    Full Text Available Tumor-initiating cells (T-ICs discovered in various tumors have been widely reported. However, T-IC populations in salivary gland tumors have yet to be elucidated. Using the established Pleomorphic Adenoma Gene-1 (Plag1 transgenic mouse model of a salivary gland tumor, we identified CD44(high (CD44(hi tumor cells, characterized by high levels of CD44 cell surface expression, as the T-ICs for pleomorphic adenomas. These CD44(hi tumor cells incorporated 5-bromo-2-deoxyuridine (BrdU, at a lower rate than their CD44(negative (CD44(neg counterparts, and also retained BrdU for a long period of time. Cell surface maker analysis revealed that 25% of the CD44(hi tumor cells co-express other cancer stem cell markers such as CD133 and CD117. As few as 500 CD44(hi tumor cells were sufficient to initiate pleomorphic adenomas in one third of the wildtype mice, whereas more than 1×10(4 CD44(neg cells were needed for the same purpose. In NIH 3T3 cells, Plag1 was capable of activating the gene transcription of Egr1, a known upregulator for CD44. Furthermore, deletion of sequence 81-96 in the Egr1 promoter region abolished the effect of Plag1 on Egr1 upregulation. Our results establish the existence of T-ICs in murine salivary gland tumors, and suggest a potential molecular mechanism for CD44 upregulation.

  9. A subset of AID-dependent B-1a cells initiates hypersensitivity and pneumococcal pneumonia resistance.

    Science.gov (United States)

    Askenase, Phillip W; Bryniarski, Krzysztof; Paliwal, Vipin; Redegeld, Frank; Groot Kormelink, Thomas; Kerfoot, Steven; Hutchinson, Andrew T; van Loveren, Henk; Campos, Regis; Itakura, Atsuko; Majewska-Szczepanik, Monika; Yamamoto, Natsuo; Nazimek, Katarzyn; Szczepanik, Marian; Ptak, Wold

    2015-12-01

    We propose that there is a special B-1a B cell subset ("sB-1a" cells) that mediates linked processes very early after immunization to initiate cutaneous contact sensitivity (CS), delayed-type hypersensitivity (DTH), and immune resistance to pneumococcal pneumonia. Our published data indicate that in CS and DTH, these initiating processes are required for elicitation of the delayed onset and late-occurring classical T cell-mediated responses. sB-1a cells resemble memory B2 cells, as they are stimulated within 1 h of immunization and depend on T helper cytokines-uniquely IL-4 from hepatic iNKT cells--for activation and rapid migration from the peritoneal cavity to the spleen to secrete IgM antibody (Ab) and Ab-derived free light chains (FLCs) by only 1 day after immunization. Unlike conventional B-1a (cB-1a) cell-produced IgM natural Ab, IgM Ab produced by sB-1a cells has high Ag affinity owing to immunoglobulin V-region mutations induced by activation-induced cytidine deaminase (AID). The dominant cB-1a cells are increased in immunized AID-deficient mice but do not mediate initiation, CS, or pneumonia resistance because natural Ab has relatively low Ag affinity because of unmutated germ-line V regions. In CS and DTH, sB-1a IgM Ag affinity is sufficiently high to mediate complement activation for generation of C5a that, together with vasoactive mediators such as TNF-α released by FLC-sensitized mast cells, activate local endothelium for extravascular recruitment of effector T cells. We conclude by discussing the possibility of functional sB-1 cells in humans. PMID:26662721

  10. The initial slope of cell survival curves. Its implications in radiotherapy

    International Nuclear Information System (INIS)

    The problem of the initial slope of the cell survival curves can be approached in 2 ways: a straightforward approach is the direct and acurate measurement of the cell survival at low dose. This method is practically restricted to experiments in vitro; an indirect approach is the determination of the initial slope of the single cell survival curves from the shape of the ''isoeffect curves'' for fractionated irradiations. This method can be applied to ''non-quantitative'' reactions. Implications in radiotherapy of the existence of a significant initial slope are presented with respect to the 3 following problems: importance of the fraction number N for fractionated irradiations with small doses per fraction and differential effect related to fraction number; variation of the total dose as a function of dose rate for low dose rate irradiation; RBE of high LET radiation and RBE/dose relationship

  11. Initial evaluation of children admitted on the Paediatric Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Esperanza Arce Delgado

    2007-09-01

    Full Text Available The initial evaluation of the child, when admitted on the Paediatric Intensive Unit, is a essential tool and key piece as a starting point on the development of a specific Care Plan for each child. Therefore, it is necessary the existence of a protocol, according to a rigorous methodology, so that cares will have quality and thus, it will be avoided that each nursing professional will act in a different way, according to his intuition, beliefs or improvisation capacity.The initial evaluation of the child will allow us not only to coordinate the interventions, but also to give continuity to the cares.The initial evaluation of the child document is a nursing register that is part of the clinical register of the paediatric patient. Nursing registers turn to be the best approximation of what nowadays is our job’s practice, and they are, therefore, necessary for us to be judged by a professional perspective and to make it possible to classify the services we carry out to the society.

  12. Specific initiation by RNA polymerase I in a whole-cell extract from yeast.

    OpenAIRE

    Schultz, M C; Choe, S Y; Reeder, R H

    1991-01-01

    A protocol is described for making a soluble whole-cell extract from yeast (Saccharomyces cerevisiae) that supports active and specific transcription initiation by RNA polymerases I, II, and III. Specific initiation by polymerase I decreases in high-density cultures, paralleling the decrease in abundance of the endogenous 35S rRNA precursor. This extract should be useful for studying the molecular mechanisms that regulate rRNA transcription in yeast.

  13. Tumor-Initiating Cells Are Enriched in CD44hi Population in Murine Salivary Gland Tumor

    OpenAIRE

    Shukun Shen; Wenjun Yang; Zhugang Wang; Xia Lei; Liqun Xu; Yang Wang; Lizhen Wang; Lei Huang; Zhiwei Yu; Xinhong Zhang; Jiang Li; Yan Chen; Xiaoping Zhao; Xuelai Yin; Chenping Zhang

    2011-01-01

    Tumor-initiating cells (T-ICs) discovered in various tumors have been widely reported. However, T-IC populations in salivary gland tumors have yet to be elucidated. Using the established Pleomorphic Adenoma Gene-1 (Plag1) transgenic mouse model of a salivary gland tumor, we identified CD44(high) (CD44(hi)) tumor cells, characterized by high levels of CD44 cell surface expression, as the T-ICs for pleomorphic adenomas. These CD44(hi) tumor cells incorporated 5-bromo-2-deoxyuridine (BrdU), at a...

  14. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Demouth, Christina; Safwat, Akmal;

    2016-01-01

    . However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin.......Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal......) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI...

  15. An Hsp70 peptide initiates NK cell killing of leukemic blasts after stem cell transplantation

    NARCIS (Netherlands)

    Gross, Catharina; Holler, Ernst; Stangl, Stefan; Dickinson, Anne; Pockley, A. Graham; Asea, Alexzander A.; Mallappa, Nagaraj; Multhoff, Gabriele

    2008-01-01

    In contrast to solid tumors, leukemic blasts frequently present both Hsp70 and HLA-E on their cell Surface and thereby present activating and inhibitory signals to CD94(+) NK cells. In the first 12 months after stem cell trail splantation (SCT) CD94(+) NK cells clearly dominate over CD3(+)/CD16(-)/5

  16. The epigenetics of tumour initiation: cancer stem cells and their chromatin.

    Science.gov (United States)

    Avgustinova, Alexandra; Benitah, Salvador Aznar

    2016-02-01

    Cancer stem cells (CSCs) have been identified in various tumours and are defined by their potential to initiate tumours upon transplantation, self-renew and reconstitute tumour heterogeneity. Modifications of the epigenome can favour tumour initiation by affecting genome integrity, DNA repair and tumour cell plasticity. Importantly, an in-depth understanding of the epigenomic alterations underlying neoplastic transformation may open new avenues for chromatin-targeted cancer treatment, as these epigenetic changes could be inherently more amenable to inhibition and reversal than hard-wired genomic alterations. Here we discuss how CSC function is affected by chromatin state and epigenomic instability. PMID:26874045

  17. The neurite-initiating effect of microbial extracellular glycolipids in PC12 cells

    OpenAIRE

    Isoda, Hiroko; Shinmoto, Hiroshi; Matsumura, Masatoshi; Nakahara, Tadaatsu

    1999-01-01

    The effects of several kinds of microbial extracellular glycolipids on neurite initiation in PC12 cells were examined. Addition of mannosylerythritol lipid-A (MEL-A), MEL-B, and sophorose lipid (SL) to PC12 cells caused significant neurite outgrowth. Other glycolipids, such as polyol lipid (PL), rhamnose lipid (RL), succinoyl trehalose lipid-A (STL-A) and STL-B caused no neurite-initiation. MEL-A increased acetylcholine esterase (AChE) activity to an extent similar to nerve growth factor (NGF...

  18. 18F-FDG PET/CT in the evaluation of gallbladder carcinoma - Initial experience

    International Nuclear Information System (INIS)

    Background: Gallbladder carcinoma, beside gastric and breast cancer, is one of the leading cause of death for cancer in Chilean women reaching a mortality rate of 12.9 per 100.000 women. The global prognosis remains poor, with global lethality around 95%. The most frequent clinical manifestations are: incidental finding in a biopsy of a laparoscopic cholecystectomy, gallbladder mass with or without jaundice and peritoneal carcinomatosis. Usually the diagnosis is too late, most patients show invasion of nearly organs and lymph nodes involvement. Like in other type of tumors, preoperative staging is essential for an adequate treatment selection. Treatment of early stage or locoregional involvement is surgery and chemo-radiotherapy. In advances stage only palliative chemotherapy or palliative cares are indicated. In local disease, imaging tests are useful for detecting lymph nodes, hilar or hepatic involvement, and to rule out spread metastases. Conventional imaging modalities, such as ultrasonography, CT, and MRI may underestimate disease extension. There are few experience of 18FDG PET-CT and gallbladder carcinoma communicated in the medical literature. Most of these publications are dealing with differential diagnosis of gallbladder tumors for detection of malignancy. In this report we present our initial experience evaluating patients suffering from gallbladder carcinoma with 18FDG PET/CT. The goal of this study was to assess the metabolic activity, localization and extension of gallbladder tumor by PET/CT. Methods: We studied prospectively 17 consecutive patients (2 males and 15 females); mean age 56.6 years (range 33 - 77) with histologically proven gallbladder carcinoma. Eleven patients were studied after cholecystectomy. The remaining were unresectable at the time of diagnosis. Clinical indications for 18FDG PET-CT were: to evaluate surgery chance in 8 patients, chemotherapy response in 2, staging and follow up in 3 and to confirm disseminated disease seen in

  19. MIF Maintains the Tumorigenic Capacity of Brain Tumor-Initiating Cells by Directly Inhibiting p53.

    Science.gov (United States)

    Fukaya, Raita; Ohta, Shigeki; Yaguchi, Tomonori; Matsuzaki, Yumi; Sugihara, Eiji; Okano, Hideyuki; Saya, Hideyuki; Kawakami, Yutaka; Kawase, Takeshi; Yoshida, Kazunari; Toda, Masahiro

    2016-05-01

    Tumor-initiating cells thought to drive brain cancer are embedded in a complex heterogeneous histology. In this study, we isolated primary cells from 21 human brain tumor specimens to establish cell lines with high tumorigenic potential and to identify the molecules enabling this capability. The morphology, sphere-forming ability upon expansion, and differentiation potential of all cell lines were indistinguishable in vitro However, testing for tumorigenicity revealed two distinct cell types, brain tumor-initiating cells (BTIC) and non-BTIC. We found that macrophage migration inhibitory factor (MIF) was highly expressed in BTIC compared with non-BTIC. MIF bound directly to both wild-type and mutant p53 but regulated p53-dependent cell growth by different mechanisms, depending on glioma cell line and p53 status. MIF physically interacted with wild-type p53 in the nucleus and inhibited its transcription-dependent functions. In contrast, MIF bound to mutant p53 in the cytoplasm and abrogated transcription-independent induction of apoptosis. Furthermore, MIF knockdown inhibited BTIC-induced tumor formation in a mouse xenograft model, leading to increased overall survival. Collectively, our findings suggest that MIF regulates BTIC function through direct, intracellular inhibition of p53, shedding light on the molecular mechanisms underlying the tumorigenicity of certain malignant brain cells. Cancer Res; 76(9); 2813-23. ©2016 AACR. PMID:26980763

  20. Impact evaluation of the Urban Health Initiative in urban Uttar Pradesh, India

    Science.gov (United States)

    Achyut, Pranita; Benson, Aimee; Calhoun, Lisa M.; Corroon, Meghan; Guilkey, David K.; Kebede, Essete; Lance, Peter M.; Mishra, Anurag; Nanda, Priya; O'Hara, Rick; Sengupta, Ranajit; Speizer, Ilene S.; Stewart, John F.; Winston, Jennifer

    2016-01-01

    Objectives The Urban Health Initiative (UHI) was initiated in 2009 with the goal of increasing family planning (FP) use among the poor in urban areas of Uttar Pradesh, India. The Measurement, Learning & Evaluation project (MLE) was tasked with rigorous impact evaluation of the UHI. This paper presents the impact evaluation findings of the UHI program. Study design The MLE design includes a longitudinal sample of women and health facilities with baseline (2010) and endline (2014) data collection in six cities in Uttar Pradesh, India. At baseline, samples representative of women in each city were selected with oversampling of the poor. Eighty-four percent of women interviewed at baseline were reinterviewed 4 years later at endline. The longitudinal data support a within/fixed-effects approach to identification of program impact on changes in modern FP use. Results Impact evaluation results show significant effects of exposure to both demand and supply side program activities. In particular, women exposed to brochures (marginal effect: 6.96, p India's strategies aimed at ensuring access to and provision of FP to urban poor populations. The effective demand- and supply-side strategies of the UHI program are therefore likely to be sustainable and scalable to other urban areas in India. Implications statement Findings from this study are important for designing sustainable and scalable FP strategies for urban India where increases in FP use will be relevant for meeting international FP targets. PMID:26948185

  1. Dynamic competition between transcription initiation and repression: Role of nonequilibrium steps in cell-to-cell heterogeneity.

    Science.gov (United States)

    Mitarai, Namiko; Semsey, Szabolcs; Sneppen, Kim

    2015-08-01

    Transcriptional repression may cause transcriptional noise by a competition between repressor and RNA polymerase binding. Although promoter activity is often governed by a single limiting step, we argue here that the size of the noise strongly depends on whether this step is the initial equilibrium binding or one of the subsequent unidirectional steps. Overall, we show that nonequilibrium steps of transcription initiation systematically increase the cell-to-cell heterogeneity in bacterial populations. In particular, this allows also weak promoters to give substantial transcriptional noise. PMID:26382435

  2. Mechanism of initial attachment of corneal epithelial cells to polymeric surfaces.

    Science.gov (United States)

    Steele, J G; Johnson, G; Griesser, H J; Underwood, P A

    1997-12-01

    The initial attachment of cultured bovine corneal epithelial cells and stromal fibroblasts to two oxygen-containing synthetic polymers was studied. Cultured epithelial cells and stromal fibroblasts were seeded onto two oxygen-containing surfaces: 'tissue culture' polystyrene (TCPS) and a polymer film deposited by RF plasma deposition using a methylmethacrylate monomer (MMA/FEP). To establish the mechanism of cell attachment, the effect of the selective removal of the vitronectin and fibronectin from the serum used in the culture medium was tested. The attachment of cultured epithelial cells during the first 90 min of culture was reduced by 40% (TCPS)-80% (MMA/FEP) as a result of removing vitronectin from the medium. Attachment of these cells to TCPS was reduced by 85-95% when the serum was depleted of both fibronectin and vitronectin. However, depletion of fibronectin reduced cell attachment to TCPS by 20%, whilst on MMA/FEP cell attachment was equivalent, or higher, than that for intact serum. The attachment of cultured corneal stromal fibroblasts was similarly dependent on vitronectin but less dependent on fibronectin. Therefore, for the attachment of both cultured epithelial cells and fibroblasts to oxygen-containing surfaces in the presence of serum, there is a high requirement for serum vitronectin but a lesser requirement for fibronectin. The effects of the establishment of corneal epithelial cells in culture and the site of origin of the cells, were determined. Primary isolates of epithelial cells isolated from the limbal, central or peripheral regions of the cornea were less dependent on vitronectin for initial attachment to TCPS than were these cells after several passages in culture. Furthermore, the primary isolates were dramatically less responsive to vitronectin than the cultured cells. These results indicate that the mechanism of attachment of corneal epithelial cells to TCPS varies with the culture experience of the cells. Cells that are culture

  3. Residual Tumor Cells That Drive Disease Relapse after Chemotherapy Do Not Have Enhanced Tumor Initiating Capacity

    OpenAIRE

    Ganapati V. Hegde; Cecile de la Cruz; Jeffrey Eastham-Anderson; Yanyan Zheng; E Alejandro Sweet-Cordero; Jackson, Erica L.

    2012-01-01

    Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs) have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the orig...

  4. Identification and Characterization of Tumor Initiating Cells in Various Mouse Mammary Tumor Models

    OpenAIRE

    Ishibashi, Tomoko

    2016-01-01

    Breast cancer is not a single disease as it can be classified into different subtypes according to cellular composition, morphology, proliferative index, genetic lesions and therapeutic responses. The molecular and cellular mechanisms underpinning tumor heterogeneity remain a central question in the cancer biology field. To explain the multitude of breast cancer phenotypes, it has been proposed that tumor-initiating cells (TICs) might originate from different cells within the mammary lineage....

  5. Apoptotic cells trigger a membrane-initiated pathway to increase ABCA1

    OpenAIRE

    Fond, Aaron M.; Lee, Chang Sup; Schulman, Ira G.; Kiss, Robert S.; Ravichandran, Kodi S.

    2015-01-01

    Macrophages clear millions of apoptotic cells daily and, during this process, take up large quantities of cholesterol. The membrane transporter ABCA1 is a key player in cholesterol efflux from macrophages and has been shown via human genetic studies to provide protection against cardiovascular disease. How the apoptotic cell clearance process is linked to macrophage ABCA1 expression is not known. Here, we identified a plasma membrane–initiated signaling pathway that drives a rapid upregulatio...

  6. Tongue metastasis as an initial presentation of renal cell carcinoma: a case report and literature review

    OpenAIRE

    Azam Faisal; Abubakerr Muneer; Gollins Simon

    2008-01-01

    Abstract Introduction Primary tumour of the kidney metastasizing to the tongue is very unusual and only anecdotal cases have been reported. An exhaustive literature review covering the period from 1911 onwards disclosed 28 cases. Out of those, only 3 cases presented initially with tongue metastases before the diagnosis of primary renal cell carcinoma. The prognosis for patients with lingual metastasis of renal cell carcinoma is poor. Treatment of tongue metastasis is usually palliative and ai...

  7. Multiple myeloma and bone marrow mesenchymal stem cells' crosstalk: Effect on translation initiation.

    Science.gov (United States)

    Attar-Schneider, Oshrat; Zismanov, Victoria; Dabbah, Mahmoud; Tartakover-Matalon, Shelly; Drucker, Liat; Lishner, Michael

    2016-09-01

    Multiple myeloma (MM) malignant plasma cells reside in the bone marrow (BM) and convert it into a specialized pre-neoplastic niche that promotes the proliferation and survival of the cancer cells. BM resident mesenchymal stem cells (BM-MSCs) are altered in MM and in vitro studies indicate their transformation by MM proximity is within hours. The response time frame suggested that protein translation may be implicated. Thus, we assembled a co-culture model of MM cell lines with MSCs from normal donors (ND) and MM patients to test our hypothesis. The cell lines (U266, ARP-1) and BM-MSCs (ND, MM) were harvested separately after 72 h of co-culture and assayed for proliferation, death, levels of major translation initiation factors (eIF4E, eIF4GI), their targets, and regulators. Significant changes were observed: BM-MSCs (ND and MM) co-cultured with MM cell lines displayed elevated proliferation and death as well as increased expression/activity of eIF4E/eIF4GI; MM cell lines co-cultured with MM-MSCs also displayed higher proliferation and death rates coupled with augmented translation initiation factors; in contrast, MM cell lines co-cultured with ND-MSCs did not display elevated proliferation only death and had no changes in eIF4GI levels/activity. eIF4E expression was increased in one of the cell lines. Our study demonstrates that there is direct dialogue between the MM and BM-MSCs populations that includes translation initiation manipulation and critically affects cell fate. Future research should be aimed at identifying therapeutic targets that may be used to minimize the collateral damage to the cancer microenvironment and limit its recruitment into the malignant process. © 2015 Wiley Periodicals, Inc. PMID:26293751

  8. Anterior prostate biopsy at initial and repeat evaluation: is it useful to detect significant prostate cancer?

    Directory of Open Access Journals (Sweden)

    Pietro Pepe

    2015-10-01

    Full Text Available ABSTRACT Purpose: Detection rate for anterior prostate cancer (PCa in men who underwent initial and repeat biopsy has been prospectively evaluated. Materials and Methods: From January 2013 to March 2014, 400 patients all of Caucasian origin (median age 63.5 years underwent initial (285 cases and repeat (115 cases prostate biopsy; all the men had negative digital rectal examination and the indications to biopsy were: PSA values > 10 ng/mL, PSA between 4.1-10 or 2.6-4 ng/mL with free/total PSA≤25% and ≤20%, respectively. A median of 22 (initial biopsy and 31 cores (repeat biopsy were transperineally performed including 4 cores of the anterior zone (AZ and 4 cores of the AZ plus 2 cores of the transition zone (TZ, respectively. Results: Median PSA was 7.9 ng/mL; overall, a PCa was found in 180 (45% patients: in 135 (47.4% and 45 (36% of the men who underwent initial and repeat biopsy, respectively. An exclusive PCa of the anterior zone was found in the 8.9 (initial biopsy vs 13.3% (repeat biopsy of the men: a single microfocus of cancer was found in the 61.2% of the cases; moreover, in 7 out 18 AZ PCa the biopsy histology was predictive of significant cancer in 2 (28.5% and 5 (71.5% men who underwent initial and repeat biopsy, respectively. Conclusions: However AZ biopsies increased detection rate for PCa (10% of the cases, the majority of AZ PCa with histological findings predictive of clinically significant cancer were found at repeat biopsy (about 70% of the cases.

  9. An Evaluation of Flash Cells Used in Critical Applications

    Science.gov (United States)

    Katz, Richard B.; Flowers, David; Bergevin, Keith

    2016-01-01

    Due to the common use of Flash technology in many commercial and industrial Programmable Logic Devices (PLDs) such as FPGAs and mixed-signal microcontrollers, flash technology is being utilized in fuzed munition applications. This presents a long-term reliability issue for both DoD and NASA safety- and mission-critical applications. A thorough understanding of the data retention failure modes and statistics associated with Flash data retention is of vital concern to the fuze safety community. A key retention parameter for a flash cell is the threshold voltage (VTH), which is an indirect indicator of the amount of charge stored on the cells floating gate. Initial test results based on a study of charge loss in flash cells in an FPGA device is presented. Statistical data taken from a small sample set indicates quantifiable charge loss for devices stored at both room temperature and 150 C. Initial evaluation of the distribution of threshold voltage in a large sample set (800 devices) is presented. The magnitude of charge loss from exposure to electrostatic discharge and electromagnetic fields is measured and presented. Simulated data (and measured data as available) resultant from harsh-environment testing (neutron, heavy ion, EMP) is presented.

  10. Endothelial cell-initiated signaling promotes the survival and self-renewal of cancer stem cells

    OpenAIRE

    Krishnamurthy, Sudha; Dong, Zhihong; Vodopyanov, Dmitry; Imai, Atsushi; Helman, Joseph I.; Prince, Mark E.; Wicha, Max S.; Jacques E Nör

    2010-01-01

    Recent studies have demonstrated that cancer stem cells play an important role in the pathobiology of head and neck squamous cell carcinomas (HNSCC). However, little is known about functional interactions between head and neck cancer stem-like cells (CSC) and surrounding stromal cells. Here, we used Aldehyde Dehydrogenase activity and CD44 expression to sort putative stem cells from primary human HNSCC. Implantation of 1,000 CSC (ALDH+CD44+Lin−) led to tumors in 13 (out of 15) mice, while 10,...

  11. Delay of ZGA initiation occurred in 2-cell blocked mouse embryos

    Institute of Scientific and Technical Information of China (English)

    JIA JING QIU; WU WEN ZHANG; ZHI LI WU; YI HONG WANG; MIN QIAN; YI PING LI

    2003-01-01

    One-cell mouse embryos from KM strain and B6C3F1 strain were cultured in M16 medium, in which2-cell block generally occurs. Embryos of KM strain exhibited 2-cell block, whereas B6C3F1 embryos,which are regarded as a nonblocking strain, proceeded to the 4-cell stage in our culture condition. It is oftenassumed that the block of early development is due to the failure of zygotic gene activation (ZGA) in culturedembryos. In this study we examined protein synthesis patterns by two-dimensional gel electrophoresis of[35S] methionine radiolabeled 2-cell embryos. Embryos from the blocking strain and the nonblocking strainwere compared in their development both in vitro and in vivo. The detection of TRC expression, a markerof ZGA, at 42 h post hCG in KM embryos developed in vitro suggested that ZGA was also initiated even inthe 2-cell arrested embryos. Nevertheless, a significant delay of ZGA was observed in KM strain as comparedwith normally developed B6C3F1 embryos. At the very beginning of major ZGA as early as 36 h post hCG,TRC has already been expressed in B6C3F1 embryos developed in vitro and KM embryos developed in vivo.But for 2-cell blocked KM embryos, TRC was still not detectable even at 38 h post hCG. These evidencessuggest that 2-cell-blocked embryos do initiate ZGA, and that 2-cell block phenomenon is due not to thedisability in initiating ZGA, but to a delay of ZGA.

  12. Research and Development of Proton-Exchange Membrane (PEM) Fuel Cell System for Transportation Applications: Initial Conceptual Design Report

    Energy Technology Data Exchange (ETDEWEB)

    1993-11-30

    This report addresses Task 1.1, model development and application, and Task 1.2, vehicle mission definition. Overall intent is to produce a methanol-fueled 10-kW power source, and to evaluate electrochemical engine (ECE) use in transportation. Major achievements include development of an ECE power source model and its integration into a comprehensive power source/electric vehicle propulsion model, establishment of candidate FCV (fuel cell powered electric vehicle) mission requirements, initial FCV studies, and a candidate FCV recommendation for further study.

  13. Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

    DEFF Research Database (Denmark)

    Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M;

    2002-01-01

    The mitral cell primary dendrite plays an important role in transmitting distal olfactory nerve input from olfactory glomerulus to the soma-axon initial segment. To understand how dendritic active properties are involved in this transmission, we have combined dual soma and dendritic patch recordi...

  14. Long-term Cultured Human Neural Stem Cells Undergo Spontaneous Transformation to Tumor-Initiating Cells

    Directory of Open Access Journals (Sweden)

    Weihua Wu, Qihua He, Xiaoxia Li, Xiaoyan Zhang, Aili Lu, Ruimin Ge, HongYing Zhen, Alfred E. Chang, Qiao Li, Li Shen

    2011-01-01

    Full Text Available In this report, we describe the spontaneous malignant transformation of long-term cultured human fetal striatum neural stem cells (hsNSCs, passage 17. After subcutaneous transplantation of long-term cultured hsNSCs into immunodeficient nude mice, 2 out of 15 mice formed xenografts which expressed neuroendocrine tumor markers CgA and NSE. T1 cells, a cell line that we derived from one of the two subcutaneous xenografts, have undergone continuous expansion in vitro. These T1 cells showed stem cell-like features and expressed neural stem cell markers nestin and CD133. The T1 cells were involved in abnormal karyotype, genomic instability and fast proliferation. Importantly, after long-term in vitro culture, the T1 cells did not result in subcutaneous xenografts, but induced intracranial tumor formation, indicating that they adjusted themselves to the intracranial microenvironment. We further found that the T1 cells exhibited an overexpressed level of EGFR, and the CD133 positive T1 cells showed a truncation mutation in the exons 2-7 of the EGFR (EGFRvIII gene. These results suggest that continuous expansion of neural stem cells in culture may lead to malignant spontaneous transformation. This phenomenon may be functionally related to EGFR by EGFRvIII gene mutation.

  15. Radiation-resistant B-1 cells: A possible initiating cells of neoplastic transformation.

    Science.gov (United States)

    Guimarães-Cunha, Caroline Ferreira; Alvares-Saraiva, Anuska Marcelino; de Souza Apostolico, Juliana; Popi, Ana Flavia

    2016-07-01

    The role of B-1 cells in the hyperproliferative hematologic disease has been described. Several reports bring evidences that B-1 cells are the main cell population in the chronic lymphatic leukemia. It is also described that these cells have an important involvement in the lupus erythematous systemic. The murine model used to investigate both disease models is NZB/NZW. Data from literature point that mutation in micro-RNA 15a and 16 are the responsible for the B-1 hyperplasia in these mice. Interestingly, it was demonstrated that NZB/NZW B-1 cells are radioresistant, contrariwise to observe in other mouse lineage derived B-1 cells and B-2 cells. However, some reports bring evidences that a small percentage of B-1 cells in healthy mice are also able to survive to irradiation. Herein, we aim to investigate the malignant potential of ionizing-radiation resistant B-1 cells in vitro. Our main goal is to establish a model that mimics the neoplastic transformation originate to a damage exposure of DNA, and not only related to intrinsic mutations. Data shown here demonstrated that radiation-resistant B-1 cells were able to survive long periods in culture. Further, these cells show proliferation index increase in relation to non-irradiated B-1 cells. In addition, radiation resistant B-1 cells showed hyperploid, morphologic alterations, increased induction of apoptosis after anti-IgM stimulation. Based on these results, we could suggest that radiation resistant B-1 cells showed some modifications in that could be related to induction of malignant potential. PMID:26898918

  16. Comparative Evaluation of the Initial Corrosion of Four Brands of High Copper Dental Amalgams

    Directory of Open Access Journals (Sweden)

    V. Mortazavi

    2004-09-01

    Full Text Available Statement of Problem: Many attempts have been made in order to evaluate the amalgam corrosion behavior as an indicator of biocompatibility. Purpose: The aim of this study was to evaluate and compare the initial corrosion of four different brands of dental amalgams. Materials and Methods: Four different types of commercial high copper dental amalgam were studied. A special mold was used and twenty-one samples of each type of commercial dental amalgams were prepared. X-ray diffraction technique was used to investigate the microstructure of freshly prepared specimens. Electrochemical potentiodynamic tests were performed in physiological solutions in order to determine and compare the corrosion behavior of freshly prepared sample of four brands of dental amalgams. The physiological solutions were the Ringer’s solution and physiological normal saline. Five replicate tests on each group of specimens were performed. Tafel extrapolation and linear polarization methods determined corrosion potentials and corrosion current densities. The mean value and standard deviations of the results were calculated. The mean values were statistically compared by ANOVA and Duncan methods at 95% level of confidence. Results: Gamma-2 phase was present in freshly prepared sample of each type of commercial amalgam. The results showed statistically significant differences between the mean corrosion current density values of freshly prepared sample of four brands of amalgams (P<0.05. The freshly prepared specimen of Sybraloy dental amalgam possesses the higher initial corrosion resistance than the other three, and Cinaalloy dental amalgam possesses the lowest corrosion resistance. This trend is independent to the type of physiological environment. Conclusion: Initial corrosion resistance of each type of commercial dental amalgam is much less than its corrosion resistance that could be obtained after one week. From the viewpoint of the corrosion behavior as an indication of

  17. The organoid-initiating cells in mouse pancreas and liver are phenotypically and functionally similar

    Directory of Open Access Journals (Sweden)

    Craig Dorrell

    2014-09-01

    Full Text Available Pancreatic Lgr5 expression has been associated with organoid-forming epithelial progenitor populations but the identity of the organoid-initiating epithelial cell subpopulation has remained elusive. Injury causes the emergence of an Lgr5+ organoid-forming epithelial progenitor population in the adult mouse liver and pancreas. Here, we define the origin of organoid-initiating cells from mouse pancreas and liver prior to Lgr5 activation. This clonogenic population was defined as MIC1-1C3+/CD133+/CD26− in both tissues and the frequency of organoid initiation within this population was approximately 5% in each case. The transcriptomes of these populations overlapped extensively and showed enrichment of epithelial progenitor-associated regulatory genes such as Sox9 and FoxJ1. Surprisingly, pancreatic organoid cells also had the capacity to generate hepatocyte-like cells upon transplantation to Fah−/− mice, indicating a differentiation capacity similar to hepatic organoids. Although spontaneous endocrine differentiation of pancreatic progenitors was not observed in culture, adenoviral delivery of fate-specifying factors Pdx1, Neurog3 and MafA induced insulin expression without glucagon or somatostatin. Pancreatic organoid cultures therefore preserve many key attributes of progenitor cells while allowing unlimited expansion, facilitating the study of fate determination.

  18. Initial evaluation of inflammatory breast cancer with fluorodeoxyglucose positron emission tomography

    OpenAIRE

    Sager, Sait; Asa, Sertac; Doner, Rana Kaya; Leblebici, Cem; Halac, Metin

    2012-01-01

    Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer. We present here 18F FDG PET/CT findings of two patients with IBC. These patients were referred to the Nuclear Medicine department for staging of IBC. FDG PET/CT images showed diffuse infiltration of breasts with multiple lymph nodes and multiple metastases in whole-body PET/CT images. FDG PET provides additional information regarding lymph nodes or distant metastases in the initial evaluation of IBC.

  19. Initial evaluation of inflammatory breast cancer with fluorodeoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer. We present here '18F FDG PET/CT findings of two patients with IBC. These patients were referred to the Nuclear Medicine department for staging of IBC. FDG PET/CT images showed diffuse infiltration of breasts with multiple lymph nodes and multiple metastases in whole-body PET/CT images. FDG PET provides additional information regarding lymph nodes or distant metastases in the initial evaluation of IBC. (author)

  20. Long-term Cultured Human Neural Stem Cells Undergo Spontaneous Transformation to Tumor-Initiating Cells

    OpenAIRE

    Weihua Wu, Qihua He, Xiaoxia Li, Xiaoyan Zhang, Aili Lu, Ruimin Ge, HongYing Zhen, Alfred E. Chang, Qiao Li, Li Shen

    2011-01-01

    In this report, we describe the spontaneous malignant transformation of long-term cultured human fetal striatum neural stem cells (hsNSCs, passage 17). After subcutaneous transplantation of long-term cultured hsNSCs into immunodeficient nude mice, 2 out of 15 mice formed xenografts which expressed neuroendocrine tumor markers CgA and NSE. T1 cells, a cell line that we derived from one of the two subcutaneous xenografts, have undergone continuous expansion in vitro. These T1 cells showed stem ...

  1. Evaluation of a patient-initiated review system in rheumatoid arthritis: an implementation trial protocol

    Directory of Open Access Journals (Sweden)

    Paudyal Priyamvada

    2012-07-01

    Full Text Available Abstract Background Rheumatoid arthritis is a chronic inflammatory condition that affects the joints causing unpredictable episodes of pain, stiffness and disability. People with rheumatoid arthritis usually require lifelong specialist follow-up but frequently have periods when their disease can be managed through self-care or that provided by their general practitioner. Compared to the traditional clinician-driven care in rheumatoid arthritis, patient-initiated care has proven to be more beneficial in terms of reducing unnecessary medical reviews, providing greater satisfaction to patients and staffs and maintaining the patient’s physical and psychological status. We aim to evaluate the implementation of a patient-initiated review system in a routine secondary care rheumatology service in a public hospital in England, where patients get the opportunity to self-manage their disease by requesting specialist reviews at times of need instead of clinician-scheduled appointments. Methods/design Three hundred and eighty patients attending routine review at Plymouth Hospitals NHS Trust will be randomised to either enrol immediately into a patient-initiated review system (direct access group, or to be seen regularly by a clinician at the hospital (regular clinician-initiated group. Patients (or their general practitioner in the direct access group can arrange a review by calling a rheumatology nurse-led advice line that enables telephone delivered clinical advice, or where appropriate, an appointment with a rheumatologist within 10 working days. Patients in the regular clinician-initiated group will attend their planned appointments at regular intervals during the intervening period of 12 months. The primary outcome of interest is patient satisfaction; secondary outcomes include service use, waiting times and clinical measures. Semi-structured, in-depth interviews will be conducted with a subset of patients and staff with the aim of identifying

  2. Evaluation of leadership skills during the simulation education course for the initial management of blunt trauma.

    Science.gov (United States)

    Schott, Eric; Brautigam, Robert T; Smola, Jacqueline; Burns, Karyl J

    2012-04-01

    Leadership skills of senior residents, trauma fellows, and a nurse practitioner were assessed during simulation training for the initial management of blunt trauma. This was a pilot, observational study, that in addition to skill development and assessment also sought to determine the need for a dedicated leadership training course for surgical residents. The study evaluated the leadership skills and adherence to Advance Trauma Life Support (ATLS) guidelines of the team leaders during simulation training. The team leaders' performances on criteria regarding prearrival planning, critical actions based on ATLS, injury identification, patient management, and communication were evaluated for each of five blunt-trauma scenarios. Although there was a statistically significant increase in leadership skills for performing ATLS critical actions, P < 0.05, there were 10 adverse events. A structured simulation program dedicated to developing skills for team leadership willbe a worthwhile endeavor at our institution. PMID:22611722

  3. Transient expression of Olig1 initiates the differentiation of neural stem cells into oligodendrocyte progenitor cells

    NARCIS (Netherlands)

    Balasubramaniyan, [No Value; Timmer, N; Kust, B; Boddeke, E; Copray, S

    2004-01-01

    In order to develop an efficient strategy to induce the in vitro differentiation of neural stem cells (NSCs) into oligodendrocyte progenitor cells (OPCs), NSCs were isolated from E14 mice and grown in medium containing epidermal growth factor and fibroblast growth factor (FGF). Besides supplementing

  4. Actinomyces naeslundii GroEL-dependent initial attachment and biofilm formation in a flow cell system.

    Science.gov (United States)

    Arai, Toshiaki; Ochiai, Kuniyasu; Senpuku, Hidenobu

    2015-02-01

    Actinomyces naeslundii is an early colonizer with important roles in the development of the oral biofilm. The effects of butyric acid, one of short chain fatty acids in A. naeslundii biofilm formation was observed using a flow cell system with Tryptic soy broth without dextrose and with 0.25% sucrose (TSB sucrose). Significant biofilms were established involving live and dead cells in TSB sucrose with 60mM butyric acid but not in concentrations of 6, 30, 40, and 50mM. Biofilm formation failed in 60mM sodium butyrate but biofilm level in 60mM sodium butyrate (pH4.7) adjusted with hydrochloric acid as 60mM butyric media (pH4.7) was similar to biofilm levels in 60mM butyric acid. Therefore, butyric acid and low pH are required for significant biofilm formation in the flow cell. To determine the mechanism of biofilm formation, we investigated initial A. naeslundii colonization in various conditions and effects of anti-GroEL antibody. The initial colonization was observed in the 60mM butyric acid condition and anti-GroEL antibody inhibited the initial colonization. In conclusion, we established a new biofilm formation model in which butyric acid induces GroEL-dependent initial colonization of A. naeslundii resulting in significant biofilm formation in a flow system. PMID:25555820

  5. Effects of UV light on DNA chain growth and replicon initiation in human cells

    International Nuclear Information System (INIS)

    Exposure of mammalian cells to 254 nm UV light produces lesions that block DNA polymerases at least on the leading strand. Using DNA fiber autoradiography the authors report here similar findings for human cells. Wild-type human cells did not exhibit signigicant blockage following exposure to 2.5 J/m2. After exposure to 5.0 J/m2, there was significant blockage immediately after exposure, but by 5 h segment lengths returned to control values. Excision-deficient human cells, on the other hand, exhibited significant blockage both immediately and 5.0 h after exposure to 2.5 J/m2. Exposure of rodent cells to UV light is also known to activate alternative sites of replication. The authors have previously shown that this activation is more pronounced and long-lived in excision-deficient Chinese hamster ovary (CHO) cells than it is in wild-type CHO cells. The authors report here that excision-deficient human cells also exhibited a marked and prolonged activation of alternative sites of replicon initiation. Wild-type human cells, on the other hand, exhibited little if any activation. (Author). 24 refs.; 4 figs.; 2 tabs

  6. The Role of Surface Receptor Density in Surface-Initiated Polymerizations for Cancer Cell Isolation.

    Science.gov (United States)

    Lilly, Jacob L; Berron, Brad J

    2016-06-01

    Fluid biopsies potentially offer a minimally invasive alternative to traditional tissue biopsies for the continual monitoring of metastatic cancer. Current established technologies for isolating circulating tumor cells (CTCs) suffer from poor purity and yield and require fixatives that preclude the collection of viable cells for longitudinal analyses of biological function. Antigen specific lysis (ASL) is a rapid, high-purity method of cell isolation based on targeted protective coatings on antigen-presenting cells and lysis depletion of unprotected antigen-negative cells. In ASL, photoinitiators are specifically labeled on cell surfaces that enable subsequent surface-initiated polymerization. Critically, the significant determinants of process yield have yet to be investigated for this emerging technology. In this work, we show that the labeling density of photoinitiators is strongly correlated with the yield of intact cells during ASL by flow cytometry analysis. Results suggest ASL is capable of delivering ∼25% of targeted cells after isolation using traditional antibody labeling approaches. Monomer formulations of two molecular weights of PEG-diacrylate (Mn ∼ 575 and 3500) are examined. The gelation response during ASL polymerization is also investigated via protein microarray analogues on planar glass. Finally, a density threshold of photoinitiator labeling required for protection during lysis is determined for both monomer formulations. These results indicate ASL is a promising technology for high yield CTC isolation for rare-cell function assays and fluid biopsies. PMID:27206735

  7. The neurite-initiating effect of microbial extracellular glycolipids in PC12 cells.

    Science.gov (United States)

    Isoda, H; Shinmoto, H; Matsumura, M; Nakahara, T

    1999-09-01

    The effects of several kinds of microbial extracellular glycolipids on neurite initiation in PC12 cells were examined. Addition of mannosylerythritol lipid-A (MEL-A), MEL-B, and sophorose lipid (SL) to PC12 cells caused significant neurite outgrowth. Other glycolipids, such as polyol lipid (PL), rhamnose lipid (RL), succinoyl trehalose lipid-A (STL-A) and STL-B caused no neurite-initiation. MEL-A increased acetylcholine esterase (AChE) activity to an extent similar to nerve growth factor (NGF). However, MEL-A induced one or two long neurites from the cell body, while NGF induced many neurites. In addition, MEL-A-induced differentiation was transient, and after 48 h, percentage of cells with neurites started to decrease in contrast to neurons induced by NGF, which occurred in a time-dependent manner. MEL-A could induce neurite outgrowth after treatment of PC12 cells with an anti-NGF receptor antibody that obstructed NGF action. These results indicate that MEL-A and NGF induce differentiation of PC12 cells through different mechanisms. PMID:19003137

  8. Experimental Evaluation of Fatigue Crack Initiation from Corroded Hemispherical Notches in Aerospace Structural Materials

    Science.gov (United States)

    Garcia, Daniel B.; Forman, Royce; Shindo, David

    2010-01-01

    A test program was developed and executed to evaluate the influence of corroded hemispherical notches on the fatigue crack initiation and propagation in aluminum 7075-T7351, 4340 steel, and D6AC steel. Surface enhancements such as shot peening and laser shock peening were also incorporated as part of the test effort with the intent of improving fatigue performance. In addition to the testing, fracture mechanics and endurance limit based analysis methods were evaluated to characterize the results with the objective of challenging typical assumptions used in modeling fatigue cracks from corrosion pits. The results specifically demonstrate that the aluminum and steel alloys behave differently with respect to fatigue crack initiation from hemispherical corrosion pits. The aluminum test results were bounded by the fracture mechanics and endurance limit models while exhibiting a general insensitivity to the residual stress field generated by shot peening. The steel specimens were better characterized by the endurance limit fatigue properties and did exhibit sensitivities to residual stresses from the shot peening and laser shock peening

  9. Mechanistic aspects of initiation and promotion in C3H/10T1/2 cells.

    Science.gov (United States)

    Boreiko, C J

    1985-01-01

    The transformation of C3H/10T1/2 cells can be made to proceed through discrete stages of initiation and promotion. Studies of the effect of cell density upon focus formation in cultures treated with MNNG and TPA suggest that initiation by MNNG is due to a relatively infrequent, irreversible event induced by a single carcinogen treatment. In contrast, promotion appears to be a reversible process requiring multiple treatments with TPA over a protracted period of time. Some evidence suggests that promotion may entail the induction of phenotypic changes which impart a growth advantage to phenotypically unstable "initiated" cell populations. The actual cellular mechanism(s) for most of the phenomena observed in C3H/10T1/2 cultures have eluded precise definition and widely divergent hypotheses have been advanced to explain transformation, initiation, and promotion. Conceivably there are multiple mechanisms responsible for each of these phenomenon. Some agents may transform by a multistage mechanism whereas others may exert their effects in a more direct fashion. Some of the foci produced by promotion may be the result of simple selective processes, others the product of more complex inductive events. Variations would thus be expected between laboratories working with different protocols and agents. As demonstrated by the possible involvement of an MCA residue in transformation, it is also apparent that fundamental technical aspects of this conceptually simple cell transformation system are poorly understood. While it is natural to develop mechanistic models based on quantitative observations of transformation, a limited understanding of the basic cell culture variables which modulate both the induction and expression of transformation dictate that caution be exercised in extrapolating the significance of such models to in vivo carcinogenesis. PMID:4053071

  10. Initial evaluation of the radioecological situation at the Semipalatinsk Test Site in the Republic of Kazakhstan

    Energy Technology Data Exchange (ETDEWEB)

    Voigt, G.; Semiochkina, N. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Strahlenschutz

    1998-12-31

    The Semipalatinsk Test Site (STS) located in the Republic of Kazakhstan (Figure 1.1) was one of the major nuclear weapon test sites of the former Soviet Union. At the site, four hundred fifty six nuclear explosions took place between 1949 and 1989 within the STS (Mikhailov et al. 1996; Dubasov et al. 1994a), resulting in radioactive contamination both within and around the STS. Incidences of radiation related illnesses in such areas may be higher than normal levels (Burkhart 1996). Published estimates of the resulting dose to the public vary according to the source, but an independent study (Grosche 1996) indicated that as many as 30,000-40,000 people could have been exposed to an average dose of 1.6 Sv (160 rem) or more (mainly due to short-lived radionuclides such as {sup 131}I). A detailed international assessment of the impact of these tests on the local population has not yet been undertaken. A current investigation under the acronym, RADTEST, includes an evaluation of Semipalatinsk as part of a broad review of internal and external doses to people arising from nuclear tests at many different sites in the world. In the context of the European Commission funded project RESTORE (Restoration Strategy for Radioactive Contaminated Ecosystems) an attempt is being made to assess the present radiolecological situation in the STS. This initial report collates currently available data published in Russian-language literature and internal CIS reports, reports from Europe and the USA, and other international literature. In this initial evaluation, only an overview of published data made available to the RESTORE project is provided and briefly discussed. In addition, further assessments including experimental work are suggested. Additional sources of data will be pursued and will be integrated with experimental results in the final evaluation report. (orig.)

  11. Initial evaluation of the radioecological situation at the Semipalatinsk Test Site in the Republic of Kazakhstan

    International Nuclear Information System (INIS)

    The Semipalatinsk Test Site (STS) located in the Republic of Kazakhstan (Figure 1.1) was one of the major nuclear weapon test sites of the former Soviet Union. At the site, four hundred fifty six nuclear explosions took place between 1949 and 1989 within the STS (Mikhailov et al. 1996; Dubasov et al. 1994a), resulting in radioactive contamination both within and around the STS. Incidences of radiation related illnesses in such areas may be higher than normal levels (Burkhart 1996). Published estimates of the resulting dose to the public vary according to the source, but an independent study (Grosche 1996) indicated that as many as 30,000-40,000 people could have been exposed to an average dose of 1.6 Sv (160 rem) or more (mainly due to short-lived radionuclides such as 131I). A detailed international assessment of the impact of these tests on the local population has not yet been undertaken. A current investigation under the acronym, RADTEST, includes an evaluation of Semipalatinsk as part of a broad review of internal and external doses to people arising from nuclear tests at many different sites in the world. In the context of the European Commission funded project RESTORE (Restoration Strategy for Radioactive Contaminated Ecosystems) an attempt is being made to assess the present radiolecological situation in the STS. This initial report collates currently available data published in Russian-language literature and internal CIS reports, reports from Europe and the USA, and other international literature. In this initial evaluation, only an overview of published data made available to the RESTORE project is provided and briefly discussed. In addition, further assessments including experimental work are suggested. Additional sources of data will be pursued and will be integrated with experimental results in the final evaluation report. (orig.)

  12. Oncolytic adenoviruses kill breast cancer initiating CD44+CD24-/low cells.

    Science.gov (United States)

    Eriksson, Minna; Guse, Kilian; Bauerschmitz, Gerd; Virkkunen, Pekka; Tarkkanen, Maija; Tanner, Minna; Hakkarainen, Tanja; Kanerva, Anna; Desmond, Renee A; Pesonen, Sari; Hemminki, Akseli

    2007-12-01

    Cancer stem cells have been indicated in the initiation of tumors and are even found to be responsible for relapses after apparently curative therapies have been undertaken. In breast cancer, they may reside in the CD44(+)CD24(-/low) population. The use of oncolytic adenoviruses presents an attractive anti-tumor approach for eradication of these cells because their entry occurs through infection and they are, therefore, not susceptible to those mechanisms that commonly render stem cells resistant to many drugs. We isolated CD44(+)CD24(-/low) cells from patient pleural effusions and confirmed stem cell-like features including oct4 and sox2 expression and Hoechst 33342 exclusion. CD44(+)CD24(-/low) cells, including the Hoechst excluding subpopulation, could be effectively killed by oncolytic adenoviruses Ad5/3-Delta24 and Ad5.pk7-Delta24. In mice, CD44(+)CD24(-/low) cells formed orthotopic breast tumors but virus infection prevented tumor formation. Ad5/3-Delta24 and Ad5.pk7-Delta24 were effective against advanced orthotopic CD44(+)CD24(-/low)-derived tumors. In summary, Ad5/3-Delta24 and Ad5.pk7-Delta24 can kill CD44(+)CD24(-/low), and also committed breast cancer cells, making them promising agents for treatment of breast cancer. PMID:17848962

  13. Cell-State Transitions Regulated by SLUG Are Critical for Tissue Regeneration and Tumor Initiation

    Directory of Open Access Journals (Sweden)

    Sarah Phillips

    2014-05-01

    Full Text Available Perturbations in stem cell activity and differentiation can lead to developmental defects and cancer. We use an approach involving a quantitative model of cell-state transitions in vitro to gain insights into how SLUG/SNAI2, a key developmental transcription factor, modulates mammary epithelial stem cell activity and differentiation in vivo. In the absence of SLUG, stem cells fail to transition into basal progenitor cells, while existing basal progenitor cells undergo luminal differentiation; together, these changes result in abnormal mammary architecture and defects in tissue function. Furthermore, we show that in the absence of SLUG, mammary stem cell activity necessary for tissue regeneration and cancer initiation is lost. Mechanistically, SLUG regulates differentiation and cellular plasticity by recruiting the chromatin modifier lysine-specific demethylase 1 (LSD1 to promoters of lineage-specific genes to repress transcription. Together, these results demonstrate that SLUG plays a dual role in repressing luminal epithelial differentiation while unlocking stem cell transitions necessary for tumorigenesis.

  14. Biological Evaluation of Single Cell Protein

    International Nuclear Information System (INIS)

    In this study, the nutritional value of single cell protein (SCP) was evaluated as a non conventional protein source produced by fermenting fungal local strains of Trichoderma longibrachiatum, Aspergillus niger, Aspergillus terreus and Penicillium funiculosum with alkali treated sugar cane bagasse. Amino acid analysis revealed that the produced SCP contains essential and non essential amino acids. Male mice were fed on normal (basal) diet which contains 18% conventional protein and served as control group. In the second (T1) and the third (T2) group, the animals were fed on a diet in which 15% and 30% of conventional protein source were replaced by SCP, respectively. At intervals of 15, 30, 45 and 60 days, mice were sacrificed and the blood samples were collected for the biochemical evaluation. The daily averages of body weight were significantly higher with group T2 than group T1. Where as, the kidney weights in groups (T1) and (T2) were significantly increased as compared with control. A non significant difference between the tested groups in the enzyme activities of AST, ALT and GSH content of liver tissue were recorded. While, cholesterol and triglycerides contents showed a significant decrease in both (T1) and (T2) groups as compared with control. The recorded values of the serum hormone (T4), ALP activities, albumin and A/G ratio did not changed by the previous treatments. Serum levels of total protein, urea, creatinine and uric acid were higher for groups (T1) and (T2) than the control group. In conclusion, partial substitution of soy bean protein in mice diet with single cell protein (15%) improved the mice growth without any adverse effects on some of the physiological functions tested

  15. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells.

    Science.gov (United States)

    Dowling, Ryan J O; Zakikhani, Mahvash; Fantus, I George; Pollak, Michael; Sonenberg, Nahum

    2007-11-15

    Metformin is used for the treatment of type 2 diabetes because of its ability to lower blood glucose. The effects of metformin are explained by the activation of AMP-activated protein kinase (AMPK), which regulates cellular energy metabolism. Recently, we showed that metformin inhibits the growth of breast cancer cells through the activation of AMPK. Here, we show that metformin inhibits translation initiation. In MCF-7 breast cancer cells, metformin treatment led to a 30% decrease in global protein synthesis. Metformin caused a dose-dependent specific decrease in cap-dependent translation, with a maximal inhibition of 40%. Polysome profile analysis showed an inhibition of translation initiation as metformin treatment of MCF-7 cells led to a shift of mRNAs from heavy to light polysomes and a concomitant increase in the amount of 80S ribosomes. The decrease in translation caused by metformin was associated with mammalian target of rapamycin (mTOR) inhibition, and a decrease in the phosphorylation of S6 kinase, ribosomal protein S6, and eIF4E-binding protein 1. The effects of metformin on translation were mediated by AMPK, as treatment of cells with the AMPK inhibitor compound C prevented the inhibition of translation. Furthermore, translation in MDA-MB-231 cells, which lack the AMPK kinase LKB1, and in tuberous sclerosis complex 2 null (TSC2(-/-)) mouse embryonic fibroblasts was unaffected by metformin, indicating that LKB1 and TSC2 are involved in the mechanism of action of metformin. These results show that metformin-mediated AMPK activation leads to inhibition of mTOR and a reduction in translation initiation, thus providing a possible mechanism of action of metformin in the inhibition of cancer cell growth. PMID:18006825

  16. Integration of polymer electrolytes in dye sensitized solar cells by initiated chemical vapor deposition

    International Nuclear Information System (INIS)

    The mesoporous titanium dioxide electrode of dye sensitized solar cells (DSSC) has been successfully filled with polymer electrolyte to replace the conventional liquid electrolyte. Polymer electrolyte was directly synthesized and deposited using the initiated chemical vapor deposition (iCVD) process, and an iodide-triiodide redox couple in different redox solvents was then incorporated into the polymer. We have investigated different candidate polymer electrolytes, including poly(2-hydroxyethyl methacrylate) (PHEMA). The open circuit voltage of cells fabricated with iCVD PHEMA was found to be higher when compared with a liquid electrolyte that is attributed to a lower rate of electron recombination.

  17. Targeting Tumor Initiating Cells through Inhibition of Cancer Testis Antigens and Notch Signaling: A Hypothesis.

    Science.gov (United States)

    Colombo, Michela; Mirandola, Leonardo; Reidy, Adair; Suvorava, Natallia; Konala, Venu; Chiaramonte, Raffaella; Grizzi, Fabio; Rahman, Rakhshanda Layeequr; Jenkins, Marjorie R; Nugyen, Diane D; Dalhbeck, Scott; Cobos, Everardo; Figueroa, Jose A; Chiriva-Internati, Maurizio

    2015-03-01

    Tumor initiating cells (TICs) differ from normal stem cells (SCs) in their ability to initiate tumorigenesis, invasive growth, metastasis and the acquisition of chemo and/or radio-resistance. Over the past years, several studies have indicated the potential role of the Notch system as a key regulator of cellular stemness and tumor development. Furthermore, the expression of cancer testis antigens (CTA) in TICs, and their role in SC differentiation and biology, has become an important area of investigation. Here, we propose a model in which CTA expression and Notch signaling interacts to maintain the sustainability of self-replicating tumor populations, ultimately leading to the development of metastasis, drug resistance and cancer progression. We hypothesize that Notch-CTA interactions in TICs offer a novel opportunity for meaningful therapeutic interventions in cancer. PMID:25901861

  18. Evaluation of initial diffusion-weighted image findings in acute stroke patients using a semiquantitative score

    International Nuclear Information System (INIS)

    We evaluated the usefulness of rating diffusion-weighted images (DWI) using a semiquantitative score modified from the Alberta Stroke Programme Early CT Score (ASPECTS) to predict deterioration of neurological symptoms in patients with hyperacute ischemic stroke who had undergone thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA). We examined 22 patients with acute stroke (14 men, 8 women, mean age 72.5 years) treated with intravenous rt-PA. All were assessed using the National Institutes of Health Stroke Scale (NIHSS) and underwent emergent magnetic resonance (MR) imaging within 3 hours and 24 hours of stroke onset. Patients were divided into a deteriorated group (16 patients), in which NIHSS scores were increased after thrombolysis, and a non-deteriorated group (6 patients). We compared the DWI score, ASPECTS, and volume of hyperintense ischemic lesion on DWI (DWI volume) of the 2 groups and examined correlations between these scores and initial NIHSS score or DWI volume. The DWI score and ASPECTS tended to be lower in the deteriorated group than the non-deteriorated group. In addition, with a cutoff value ≤7, the DWI score could discriminate the deteriorated group from the non-deteriorated group with a sensitivity of 50% and specificity of 87.5%, whereas for ASPECTS, sensitivity was 50% and specificity, 81.2%. The DWI score, ASPECTS, and DWI volume had no correlation with NIHSS score but weak negative correlations with the DWI volume (P<0.01; Spearman's test). Comparing initial NIHSS score with each DWI score and DWI volume, the non-deteriorated group tended to have higher DWI scores and smaller DWI volumes than the deteriorated group, but there was no statistical difference between initial NIHSS and DWI scores. Though the DWI score was not statistically different, the threshold would be set to 6 points or above. Comparing initial DWI score with volume, patients with low DWI scores tended to show large variation in DWI volume and

  19. The initial evaluation in the specialized educational services: dilemmas and consequences

    Directory of Open Access Journals (Sweden)

    Fabiane Romano de Souza Bridi

    2012-11-01

    Full Text Available This article focus on the evaluation process of the group of subjects named as “students with mental retardation” in the school context. Through the theoretical contribution of the systemic thinking, this work deals with the dilemmas lived by a group of teachers when they conducted the initial evaluation of the students in the specialized educational services context. As a result of the pedagogical evaluation, we have the decision related to the frequency (or not of the scholar in the specialized educational services and the insertion (or not of this pupil into one of the categories of School Census MEC/INEP. This process, there are the tenuous contours between learning disabilities and mental retardation. It must be observed the choice of some teachers to deal with pupils with learning disabilities. Through the scope of this option it´s possible to notice different movements that position the subject, attributing to him a place: students with learning disabilities who do not attend the service; students with learning disabilities who attend the service, but are not inserted in the school census MEC/INEP; students with learning disabilities who attend the service and are inserted in the school census MEC/INEP in the category of mental retardation. And still, it receives important relevance, the distressful weight of the responsibility of attaching a student to the category of mental retardation through the pedagogical action.

  20. Indoleamine-2,3-dioxygenase elevated in tumor-initiating cells is suppressed by mitocans

    Czech Academy of Sciences Publication Activity Database

    Stapelberg, M.; Zobalová, Renata; Nguyen, M.N.; Walker, T.; Stantic, M.; Goodwin, J.; Pasdar, E.A.; Thai, T.; Prokopová, Kateřina; Yan, B.; Hall, S.; de Pennington, N.; Thomas, S.R.; Grant, G.; Štursa, Jan; Bajziková, Martina; Meedeniya, A.C.B.; Truksa, Jaroslav; Ralph, S. J.; Ansorge, O.; Dong, L.-F.; Neužil, Jiří

    2014-01-01

    Roč. 67, FEB (2014), s. 41-50. ISSN 0891-5849 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA ČR GAP305/12/1708 Institutional support: RVO:86652036 ; RVO:61388963 Keywords : IDO * Tumor-initiating cells * Mitocans * Mitochondrially targeted vitamin E succinate Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.736, year: 2014

  1. Red Blood Cell Transfusion Independence Following the Initiation of Iron Chelation Therapy in Myelodysplastic Syndrome

    OpenAIRE

    Leitch, Heather A.; Vickars, Linda M.; Chase, Jocelyn M.; Badawi, Maha A.

    2010-01-01

    Iron chelation therapy is often used to treat iron overload in patients requiring transfusion of red blood cells (RBC). A 76-year-old man with MDS type refractory cytopenia with multilineage dysplasia, intermediate-1 IPSS risk, was referred when he became transfusion dependent. He declined infusional chelation but subsequently accepted oral therapy. Following the initiation of chelation, RBC transfusion requirement ceased and he remained transfusion independent over 40 months later. Over the ...

  2. Oncogenic KRAS activates an embryonic stem cell-like program in human colon cancer initiation

    OpenAIRE

    Le Rolle, Anne-France; Chiu, Thang K.; Zeng, Zhaoshi; Shia, Jinru; Weiser, Martin R; Paty, Philip B.; Chiu, Vi K

    2016-01-01

    Colorectal cancer is the third most frequently diagnosed cancer worldwide. Prevention of colorectal cancer initiation represents the most effective overall strategy to reduce its associated morbidity and mortality. Activating KRAS mutation (KRASmut ) is the most prevalent oncogenic driver in colorectal cancer development, and KRASmut inhibition represents an unmet clinical need. We apply a systems-level approach to study the impact of KRASmut on stem cell signaling during human colon cancer i...

  3. Pulmonary Langerhans cell histiocytosis: the many faces of presentation at initial CT scan

    OpenAIRE

    Castoldi, M. C.; A. Verrioli; De Juli, E.; Vanzulli, A.

    2014-01-01

    Objectives Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial granulomatous disease that usually affects young adults who are smokers. Chest computed tomography (CT) allows a confident diagnosis of PLCH only in typical presentation, when nodules, cavitated nodules and cysts coexist and predominate in the upper and middle lungs. Methods This article includes a pictorial essay of typical and atypical presentations of PLCH at initial chest CT. Various appearances of PLCH are i...

  4. FGFR2 Promotes Breast Tumorigenicity through Maintenance of Breast Tumor-Initiating Cells

    OpenAIRE

    Kim, Sungeun; Dubrovska, Anna; Salamone, Richard J.; Walker, John R.; Grandinetti, Kathryn B.; Bonamy, Ghislain M.C.; Orth, Anthony P.; Elliott, Jimmy; Porta, Diana Graus; Garcia-Echeverria, Carlos; Reddy, Venkateshwar A.

    2013-01-01

    Emerging evidence suggests that some cancers contain a population of stem-like TICs (tumor-initiating cells) and eliminating TICs may offer a new strategy to develop successful anti-cancer therapies. As molecular mechanisms underlying the maintenance of the TIC pool are poorly understood, the development of TIC-specific therapeutics remains a major challenge. We first identified and characterized TICs and non-TICs isolated from a mouse breast cancer model. TICs displayed increased tumorigenic...

  5. Prdm14 initiates lymphoblastic leukemia after expanding a population of cells resembling common lymphoid progenitors

    OpenAIRE

    E J Dettman; Simko, Stephen J.; Ayanga, Bernard; Carofino, Brandi; Margolin, Judith; Morse, Herbert C.; Justice, Monica J.

    2011-01-01

    Understanding the heterogeneous genetic mechanisms of tumor initiation in lymphoid leukemias (LL) will lead to improvements in prognostic classification and treatment regimens. In previous studies of mouse leukemias, we showed that retroviral insertion at the Evi32 locus leads to increased expression of Prdm14, a pluripotency gene implicated in the self-renewal capacity of embryonic stem cells and the early stages of breast cancer. Here we show that PRDM14 is also overexpressed in ~25% of hum...

  6. Combining a BCL2 Inhibitor with the Retinoid Derivative Fenretinide Targets Melanoma Cells Including Melanoma Initiating Cells

    OpenAIRE

    Mukherjee, Nabanita; Reuland, Steven N.; Lu, Yan; Luo, Yuchun; Lambert, Karoline; Fujita, Mayumi; Robinson, William A.; Robinson, Steven E.; David A Norris; Yiqun G Shellman

    2014-01-01

    Investigations from multiple laboratories support the existence of melanoma initiating cells (MICs) that potentially contribute to melanoma's drug resistance. ABT-737, a small molecule BCL-2/BCL-XL/BCL-W inhibitor, is promising in cancer treatments, but not very effective against melanoma, with the anti-apoptotic protein MCL-1 as the main contributor to resistance. The synthetic retinoid fenretinide (4-HPR) has shown promise for treating breast cancers. Here, we tested whether the combination...

  7. The Akt1/IL-6/STAT3 pathway regulates growth of lung tumor initiating cells

    Science.gov (United States)

    Malanga, Donatella; De Marco, Carmela; Guerriero, Ilaria; Colelli, Fabiana; Rinaldo, Nicola; Scrima, Marianna; Mirante, Teresa; De Vitis, Claudia; Zoppoli, Pietro; Ceccarelli, Michele; Riccardi, Miriam; Ravo, Maria; Weisz, Alessandro; Federico, Antonella; Franco, Renato; Rocco, Gaetano; Mancini, Rita; Rizzuto, Antonia; Gulletta, Elio; Ciliberto, Gennaro; Viglietto, Giuseppe

    2015-01-01

    Here we report that the PI3K/Akt1/IL-6/STAT3 signalling pathway regulates generation and stem cell-like properties of Non-Small Cell Lung Cancer (NSCLC) tumor initiating cells (TICs). Mutant Akt1, mutant PIK3CA or PTEN loss enhances formation of lung cancer spheroids (LCS), self-renewal, expression of stemness markers and tumorigenic potential of human immortalized bronchial cells (BEAS-2B) whereas Akt inhibition suppresses these activities in established (NCI-H460) and primary NSCLC cells. Matched microarray analysis of Akt1-interfered cells and LCSs identified IL-6 as a critical target of Akt signalling in NSCLC TICs. Accordingly, suppression of Akt in NSCLC cells decreases IL-6 levels, phosphorylation of IkK and IkB, NF-kB transcriptional activity, phosphorylation and transcriptional activity of STAT3 whereas active Akt1 up-regulates them. Exposure of LCSs isolated from NSCLC cells to blocking anti-IL-6 mAbs, shRNA to IL-6 receptor or to STAT3 markedly reduces the capability to generate LCSs, to self-renew and to form tumors, whereas administration of IL-6 to Akt-interfered cells restores the capability to generate LCSs. Finally, immunohistochemical studies in NSCLC patients demonstrated a positive correlative trend between activated Akt, IL-6 expression and STAT3 phosphorylation (n = 94; p TICs through a NF-kB/IL-6/STAT3 pathway and provide novel potential therapeutic targets for eliminating these malignant cells in NSCLC. PMID:26486080

  8. Bone scintigraphy in the initial evaluation of dogs with primary bone tumors

    International Nuclear Information System (INIS)

    Bone scintigraphy was performed as part of an initial diagnostic evaluation of 70 dogs admitted with primary bone tumors during a 2-year period. Tumors involved major long bones of the appendicular skeleton and included 62 osteosarcomas, 6 fibrosarcomas, and 2 chondrosarcomas. All dogs were free of radiographically detectable pulmonary metastases. Bone scintigraphy was not of value in distinguishing among various types of primary tumors. One dog with an ulnar chondrosarcoma had a scintigraphically detectable occult osseous metastasis or synchronous primary tumor, and 1 dog with osteosarcoma had a scintigraphically detectable lymph node metastasis. Pulmonary metastases were not detected scintigraphically. Of the 70 dogs, 44.3% had areas of increased isotope uptake associated with nonneoplastic disease processes

  9. Evaluation of abdominal CT in the initial treatment of abdominal trauma

    International Nuclear Information System (INIS)

    During the last four years 102 patients with abdominal trauma were examined by CT for preoperative evaluation in our hospital. In 35 patients (34 %), the CT scans revealed no abnormal findings. They were all managed conservatively except for one case of perforated small bowel. In 67 patients (66 %) CT revealed evidences of substantial abdominal or retroperitoneal trauma. In 30 of them CT findings were confirmed by surgery. Hepatic injury is usually easily recognized by CT. CT is also useful for the detection of renal or splenic injuries. The majority of those parenchymatous organ injuries were successfully managed with conservative therapy, despite apparent traumatic lesions revealed by CT. Repeat CT scans is proved to be very useful to follow the changes of these traumatic lesions. In conclusion, application of abdominal CT is extremely useful for the initial decision making in treatment of patients with abdominal trauma and for the follow-up observation of injured lesions. (author)

  10. Accuracy evaluation of initialization-free registration for intraoperative 3D-navigation

    International Nuclear Information System (INIS)

    Purpose An initialization-free approach for perioperative registration in functional endoscopic sinus surgery (FESS) is sought. The quality of surgical navigation relies on registration accuracy of preoperative images to the patient. Although landmark-based registration is fast, it is prone to human operator errors. This study evaluates the accuracy of two well-known methods for segmentation of the occipital bone from CT-images for use in surgical 3D-navigation. Method The occipital bone was segmented for registration without pre-defined correspondences, with the iterative closest point algorithm (ICP). The thresholding plus marching cubes segmentation (TMCS), and the deformable model segmentation (DMS) were compared quantitatively by overlaying the areas of the segmentations in cross-sectional slices, and visually by displaying the pointwise distances between the segmentations in a three-dimensional distance map relative to an expert manual segmentation, taken as a ''ground truth''. Results Excellent correspondence between the two methods was achieved; the results showed, however, that the TMCS is closer to the ''ground truth''. This is due to the sub-voxel accuracy of the marching cubes algorithm by definition, and the sensitivity of the DMS method to the choice of parameters. The DMS approach, as a gradient-based method, is insensitive to the thresholding initialization. For noisy images and soft tissue delineation a gradient-based method, like the deformable model, performs better. Both methods correspond within minute differences less than 4%. Conclusion These results will allow further minimization of human interaction in the planning phase for intraoperative 3D-navigation, by allowing to automatically create surface patches for registration purposes, ultimately allowing to build an initialization-free, fully automatic registration procedure for navigated Ear-, Nose-, Throat- (ENT) surgery. (orig.)

  11. Accuracy evaluation of initialization-free registration for intraoperative 3D-navigation

    Energy Technology Data Exchange (ETDEWEB)

    Diakov, Georgi; Freysinger, Wolfgang [University Clinic of Oto-, Rhino-, Laryngology, Innsbruck Medical University, 4D Visualization Laboratory, Innsbruck (Austria)

    2007-08-15

    Purpose An initialization-free approach for perioperative registration in functional endoscopic sinus surgery (FESS) is sought. The quality of surgical navigation relies on registration accuracy of preoperative images to the patient. Although landmark-based registration is fast, it is prone to human operator errors. This study evaluates the accuracy of two well-known methods for segmentation of the occipital bone from CT-images for use in surgical 3D-navigation. Method The occipital bone was segmented for registration without pre-defined correspondences, with the iterative closest point algorithm (ICP). The thresholding plus marching cubes segmentation (TMCS), and the deformable model segmentation (DMS) were compared quantitatively by overlaying the areas of the segmentations in cross-sectional slices, and visually by displaying the pointwise distances between the segmentations in a three-dimensional distance map relative to an expert manual segmentation, taken as a ''ground truth''. Results Excellent correspondence between the two methods was achieved; the results showed, however, that the TMCS is closer to the ''ground truth''. This is due to the sub-voxel accuracy of the marching cubes algorithm by definition, and the sensitivity of the DMS method to the choice of parameters. The DMS approach, as a gradient-based method, is insensitive to the thresholding initialization. For noisy images and soft tissue delineation a gradient-based method, like the deformable model, performs better. Both methods correspond within minute differences less than 4%. Conclusion These results will allow further minimization of human interaction in the planning phase for intraoperative 3D-navigation, by allowing to automatically create surface patches for registration purposes, ultimately allowing to build an initialization-free, fully automatic registration procedure for navigated Ear-, Nose-, Throat- (ENT) surgery. (orig.)

  12. Youth mental health first aid: a description of the program and an initial evaluation

    Directory of Open Access Journals (Sweden)

    Jorm Anthony F

    2011-01-01

    Full Text Available Abstract Background Adolescence is the peak age of onset for mental illness, with half of all people who will ever have a mental illness experiencing their first episode prior to 18 years of age. Early onset of mental illness is a significant predictor for future episodes. However, adolescents and young adults are less likely than the population as a whole to either seek or receive treatment for a mental illness. The knowledge and attitudes of the adults in an adolescent's life may affect whether or not help is sought, and how quickly. In 2007, the Youth Mental Health First Aid Program was launched in Australia with the aim to teach adults, who work with or care for adolescents, the skills needed to recognise the early signs of mental illness, identify potential mental health-related crises, and assist adolescents to get the help they need as early as possible. This paper provides a description of the program, some initial evaluation and an outline of future directions. Methods The program was evaluated in two ways. The first was an uncontrolled trial with 246 adult members of the Australian public, who completed questionnaires immediately before attending the 14 hour course, one month later and six months later. Outcome measures were: recognition of schizophrenia or depression; intention to offer and confidence in offering assistance; stigmatising attitudes; knowledge about adolescent mental health problems and also about the Mental Health First Aid action plan. The second method of evaluation was to track the uptake of the program, including the number of instructors trained across Australia to deliver the course, the number of courses they delivered, and the uptake of the YMHFA Program in other countries. Results The uncontrolled trial found improvements in: recognition of schizophrenia; confidence in offering help; stigmatising attitudes; knowledge about adolescent mental health problems and application of the Mental Health First Aid action

  13. Evaluation of the hepatitis C virus-infected patient: the initial encounter.

    Science.gov (United States)

    Bräu, Norbert

    2013-03-01

    Deaths from hepatitis C virus (HCV)-related disease are increasing, now exceeding those from human immunodeficiency virus. Up to 7 million Americans (2.3%) may be infected with HCV, and more than half are undiagnosed. Proposed expansion of hepatitis C screening to include all persons born between 1945 and 1965 will lead to many new diagnoses, and infectious diseases physicians have a unique opportunity to be part of managing these patients. Apart from a liver-focused history and examination, the initial evaluation includes determination of the liver function via serum tests and assessment of liver fibrosis and necroinflammation through biopsy or noninvasive means. Patients with cirrhosis require screening for esophageal varices and for liver cancer. Nonimmune patients need vaccinations against hepatitis A and B, and alcohol abstinence is critical. Initial counseling on therapy emphasizes viral cure rates of currently 70%-80% as well as expected side effects. New treatments with fewer side effects and potentially higher cure rates are currently in development. PMID:23243172

  14. NOTCH1 signaling promotes human T-cell acute lymphoblastic leukemia initiating cell regeneration in supportive niches.

    Directory of Open Access Journals (Sweden)

    Wenxue Ma

    Full Text Available BACKGROUND: Leukemia initiating cells (LIC contribute to therapeutic resistance through acquisition of mutations in signaling pathways, such as NOTCH1, that promote self-renewal and survival within supportive niches. Activating mutations in NOTCH1 occur commonly in T cell acute lymphoblastic leukemia (T-ALL and have been implicated in therapeutic resistance. However, the cell type and context specific consequences of NOTCH1 activation, its role in human LIC regeneration, and sensitivity to NOTCH1 inhibition in hematopoietic microenvironments had not been elucidated. METHODOLOGY AND PRINCIPAL FINDINGS: We established humanized bioluminescent T-ALL LIC mouse models transplanted with pediatric T-ALL samples that were sequenced for NOTCH1 and other common T-ALL mutations. In this study, CD34(+ cells from NOTCH1(Mutated T-ALL samples had higher leukemic engraftment and serial transplantation capacity than NOTCH1(Wild-type CD34(+ cells in hematopoietic niches, suggesting that self-renewing LIC were enriched within the NOTCH1(Mutated CD34(+ fraction. Humanized NOTCH1 monoclonal antibody treatment reduced LIC survival and self-renewal in NOTCH1(Mutated T-ALL LIC-engrafted mice and resulted in depletion of CD34(+CD2(+CD7(+ cells that harbor serial transplantation capacity. CONCLUSIONS: These results reveal a functional hierarchy within the LIC population based on NOTCH1 activation, which renders LIC susceptible to targeted NOTCH1 inhibition and highlights the utility of NOTCH1 antibody targeting as a key component of malignant stem cell eradication strategies.

  15. IKKβ in intestinal mesenchymal cells promotes initiation of colitis-associated cancer.

    Science.gov (United States)

    Koliaraki, Vasiliki; Pasparakis, Manolis; Kollias, George

    2015-12-14

    The importance of mesenchymal cells in inflammation and/or neoplastic transformation is well recognized, but their role in the initiation of these processes, particularly in the intestine, remains elusive. Using mouse models of colorectal cancer, we show that IKKβ in intestinal mesenchymal cells (IMCs) is critically involved in colitis-associated, but not spontaneous tumorigenesis. We further demonstrate that IMC-specific IKKβ is involved in the initiation of colitis-associated cancer (CAC), as in its absence mice develop reduced immune cell infiltration, epithelial cell proliferation, and dysplasia at the early stages of the disease. At the molecular level, these effects are associated with decreased early production of proinflammatory and protumorigenic mediators, including IL-6, and reduced STAT3 activation. Ex vivo IKKβ-deficient IMCs show defective responses to innate immune stimuli such as LPS, as shown by decreased NF-κB signaling and reduced expression of important NF-κB target genes. Collectively, our results reveal a hitherto unknown role of mesenchymal IKKβ in driving inflammation and enabling carcinogenesis in the intestine. PMID:26621453

  16. MicroRNA Regulation of Brain Tumour Initiating Cells in Central Nervous System Tumours

    Directory of Open Access Journals (Sweden)

    Neha Garg

    2015-01-01

    Full Text Available CNS tumours occur in both pediatric and adult patients and many of these tumours are associated with poor clinical outcome. Due to a paradigm shift in thinking for the last several years, these tumours are now considered to originate from a small population of stem-like cells within the bulk tumour tissue. These cells, termed as brain tumour initiating cells (BTICs, are perceived to be regulated by microRNAs at the posttranscriptional/translational levels. Proliferation, stemness, differentiation, invasion, angiogenesis, metastasis, apoptosis, and cell cycle constitute some of the significant processes modulated by microRNAs in cancer initiation and progression. Characterization and functional studies on oncogenic or tumour suppressive microRNAs are made possible because of developments in sequencing and microarray techniques. In the current review, we bring recent knowledge of the role of microRNAs in BTIC formation and therapy. Special attention is paid to two highly aggressive and well-characterized brain tumours: gliomas and medulloblastoma. As microRNA seems to be altered in the pathogenesis of many human diseases, “microRNA therapy” may now have potential to improve outcomes for brain tumour patients. In this rapidly evolving field, further understanding of miRNA biology and its contribution towards cancer can be mined for new therapeutic tools.

  17. A Quest for Initiating Cells of Head and Neck Cancer and Their Treatment

    International Nuclear Information System (INIS)

    The biology of head and neck squamous cell carcinomas (HNSCC) and other cancers have been related to cancer stem-like cells (CSC). Specific markers, which vary considerably depending on tumor type or tissue of origin, characterize CSC. CSC are cancer initiating, sustaining and mostly quiescent. Compared to bulk tumors, CSC are less sensitive to chemo- and radiotherapy and may have low immunogenicity. Therapeutic targeting of CSC may improve clinical outcome. HNSCC has two main etiologies: human papillomavirus, a virus infecting epithelial stem cells, and tobacco and alcohol abuse. Here, current knowledge of HNSCC-CSC biology is reviewed and parallels to CSC of other origin are drawn where necessary for a comprehensive picture

  18. A Quest for Initiating Cells of Head and Neck Cancer and Their Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chao [Department of Otolaryngology and Head and Neck Surgery Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin (Germany); Department of Head and Neck Surgery, Zhejiang Cancer Hospital (China); Köberle, Beate [Institute of Toxicology, University Medical Center, Mainz (Germany); Kaufmann, Andreas M. [Clinic for Gynecology, Charité-Universitätsmedizin Berlin, Berlin (Germany); Albers, Andreas E., E-mail: andreas.albers@charite.de [Department of Otolaryngology and Head and Neck Surgery Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin (Germany)

    2010-07-27

    The biology of head and neck squamous cell carcinomas (HNSCC) and other cancers have been related to cancer stem-like cells (CSC). Specific markers, which vary considerably depending on tumor type or tissue of origin, characterize CSC. CSC are cancer initiating, sustaining and mostly quiescent. Compared to bulk tumors, CSC are less sensitive to chemo- and radiotherapy and may have low immunogenicity. Therapeutic targeting of CSC may improve clinical outcome. HNSCC has two main etiologies: human papillomavirus, a virus infecting epithelial stem cells, and tobacco and alcohol abuse. Here, current knowledge of HNSCC-CSC biology is reviewed and parallels to CSC of other origin are drawn where necessary for a comprehensive picture.

  19. Scalable Production of Glioblastoma Tumor-initiating Cells in 3 Dimension Thermoreversible Hydrogels.

    Science.gov (United States)

    Li, Qiang; Lin, Haishuang; Wang, Ou; Qiu, Xuefeng; Kidambi, Srivatsan; Deleyrolle, Loic P; Reynolds, Brent A; Lei, Yuguo

    2016-01-01

    There is growing interest in developing drugs that specifically target glioblastoma tumor-initiating cells (TICs). Current cell culture methods, however, cannot cost-effectively produce the large numbers of glioblastoma TICs required for drug discovery and development. In this paper we report a new method that encapsulates patient-derived primary glioblastoma TICs and grows them in 3 dimension thermoreversible hydrogels. Our method allows long-term culture (~50 days, 10 passages tested, accumulative ~>10(10)-fold expansion) with both high growth rate (~20-fold expansion/7 days) and high volumetric yield (~2.0 × 10(7) cells/ml) without the loss of stemness. The scalable method can be used to produce sufficient, affordable glioblastoma TICs for drug discovery. PMID:27549983

  20. Development of cancer-initiating cells and immortalizedcells with genomic instability

    Institute of Scientific and Technical Information of China (English)

    Ken-ichi Yoshioka; Yuko Atsumi; Hitoshi Nakagama; Hirobumi Teraoka

    2015-01-01

    Cancers that develop after middle age usually exhibitgenomic instability and multiple mutations. This is indirect contrast to pediatric tumors that usually developas a result of specific chromosomal translocations andepigenetic aberrations. The development of genomicinstability is associated with mutations that contributeto cellular immortalization and transformation. Canceroccurs when cancer-initiating cells (CICs), also calledcancer stem cells, develop as a result of these mutations.In this paper, we explore how CICs develop as a resultof genomic instability, including looking at which cancersuppression mechanisms are abrogated. A recent in vitrostudy revealed the existence of a CIC induction pathwayin differentiating stem cells. Under aberrant differentiationconditions, cells become senescent and develop genomicinstabilities that lead to the development of CICs. Theresulting CICs contain a mutation in the alternativereading frame of CDKN2A (ARF)/p53 module, i.e. , ineither ARF or p53. We summarize recently establishedknowledge of CIC development and cellular immortality,explore the role of the ARF/p53 module in protectingcells from transformation, and describe a risk factorfor genomic destabilization that increases during theprocess of normal cell growth and differentiation and isassociated with the downregulation of histone H2AX tolevels representative of growth arrest in normal cells.

  1. Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling

    Directory of Open Access Journals (Sweden)

    Huang Chih-Yang

    2010-10-01

    Full Text Available Abstract Background Head and neck squamous cell carcinoma (HNSCC is a highly lethal cancer that contains cellular and functional heterogeneity. Previously, we enriched a subpopulation of highly tumorigenic head and neck cancer initiating cells (HN-CICs from HNSCC. However, the molecular mechanisms by which to govern the characteristics of HN-CICs remain unclear. GRP78, a stress-inducible endoplasmic reticulum chaperone, has been reported to play a crucial role in the maintenance of embryonic stem cells, but the role of GRP78 in CICs has not been elucidated. Results Initially, we recognized GRP78 as a putative candidate on mediating the stemness and tumorigenic properties of HN-CICs by differential systemic analyses. Subsequently, cells with GRP78 anchored at the plasma membrane (memGRP78+ exerted cancer stemness properties of self-renewal, differentiation and radioresistance. Of note, xenotransplantation assay indicated merely 100 memGRP78+ HNSCCs resulted in tumor growth. Moreover, knockdown of GRP78 significantly reduced the self-renewal ability, side population cells and expression of stemness genes, but inversely promoted cell differentiation and apoptosis in HN-CICs. Targeting GRP78 also lessened tumorigenicity of HN-CICs both in vitro and in vivo. Clinically, co-expression of GRP78 and Nanog predicted the worse survival prognosis of HNSCC patients by immunohistochemical analyses. Finally, depletion of GRP78 in HN-CICs induced the expression of Bax, Caspase 3, and PTEN. Conclusions In summary, memGRP78 should be a novel surface marker for isolation of HN-CICs, and targeting GRP78 signaling might be a potential therapeutic strategy for HNSCC through eliminating HN-CICs.

  2. Comparative Analysis of Media and Supplements on Initiation and Expansion of Adipose-Derived Stem Cells.

    Science.gov (United States)

    Riis, Simone; Nielsen, Frederik Mølgaard; Pennisi, Cristian Pablo; Zachar, Vladimir; Fink, Trine

    2016-03-01

    Adipose-derived stem cells (ASCs) are being tested in clinical trials related to cell-based regenerative therapies. Although most of the current expansion protocols for ASCs use fetal calf serum (FCS), xenogeneic-free medium supplements are greatly desired. This study aims to compare the effect of FCS, human platelet lysate (hPL), and a fully defined medium on the initiation and maintenance of ASC cultures. ASCs obtained from five donors were cultured in five different media: StemPro, Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% hPL, or α-minimum essential medium (A-MEM) supplemented with 5% hPL, 10% hPL, or 10% FCS. The effect of media on proliferation, colony-forming units (CFUs), attachment, and morphology was assessed along with cell size, granularity, and immunophenotype. StemPro greatly compromised the initiation of ASC cultures, which could not survive more than a few passages. Cells cultured in A-MEM proliferated at a faster rate than in DMEM, and hPL significantly enhanced cell size, granularity, and proliferation compared with FCS. All media except StemPro supported CFUs equally well. Analysis of surface markers revealed higher levels of CD73 and CD105 in FCS-cultured ASCs, whereas increased levels of CD146 were found in hPL-cultured cells. Multiparametric flow cytometric analysis performed after seven passages revealed the existence of four distinct ASC subpopulations, all positive for CD73, CD90, and CD105, which mainly differed by their expression of CD146 and CD271. Analysis of the different subpopulations might represent an important biological measure when assessing different medium formulations for a particular clinical application. PMID:26838270

  3. Evaluation of a Mouse Embryonic Stem Cell Adherent Cell Differentiation and Cytotoxicity (ACDC) assay (SOT)

    Science.gov (United States)

    The Embryonic Stem Cell Test (EST) has been used to evaluate the effects of xenobiotics using three endpoints, stem cell differentiation, stem cell viability and 3T3-cell viability. Our research goal is to establish amodel system that would evaluate chemical effects using a singl...

  4. F-18 FDG PET in the initial evaluation of high risk melanoma

    International Nuclear Information System (INIS)

    positive value and negative predictive value of respectively 2,2, 97, 50 and 42%. Discussion. - FDG PET did not identify distant metastatic disease in our population of 87 high risk melanoma patients. It was true positive in 4 patients for regional nodal disease for whom sentinel node biopsy showed or might have showed nodal involvement. Another study evaluating PET FDG in melanomas thicker than 4 mm recently concluded to not include FDG PET in the initial work up of melanoma patients. However, we know that a certain percentage of these patients are likely to develop metastatic disease between 16 and 23 months after diagnosis. FDG PET could be useful in the follow up of high risk patients as suggested by a recent study. (author)

  5. A critical role for proinflammatory behavior of smooth muscle cells in hemodynamic initiation of intracranial aneurysm.

    Directory of Open Access Journals (Sweden)

    Max Mandelbaum

    Full Text Available BACKGROUND: Intracranial aneurysm initiation is poorly understood, although hemodynamic insult is believed to play an important role in triggering the pathology. It has recently been found in a rabbit model that while macrophages are absent during hemodynamic aneurysm initiation, matrix metalloproteinases (MMPs are elevated and co-localize with smooth muscle cells (SMCs. This study investigates whether SMCs play a mechanistic role in aneurysm initiation triggered by hemodynamics. METHODS: Aneurysmal damage was induced at the basilar terminus via bilateral common carotid artery ligation in rabbits (n = 45, plus 7 sham controls. 16 ligated rabbits were treated with doxycycline to inhibit MMPs, 7 received clodronate liposomes to deplete circulating monocytes, and the rest received no drug. Effects of the treatments on aneurysm development were assessed histologically 5 days and 6 months after ligation. MMP production and expression of inflammatory markers by SMCs was monitored by immunohistochemistry and in situ hybridization. RESULTS: Treatment with doxycycline attenuated aneurysmal development examined at 5 days and 6 months, suggesting that MMPs contribute to aneurysm initiation. However, systemic depletion of macrophages did not decrease MMPs or suppress aneurysmal development. Immunofluorescence showed that during aneurysm initiation MMP-2 and MMP-9 were distributed in SMCs, and in situ hybridization indicated that they were transcribed by SMCs. In regions of early aneurysmal lesion, SMCs exhibited decreased expression of smooth muscle actin and increased NF-κB and MCP-1 expressions. CONCLUSIONS: During aneurysm initiation triggered by hemodynamics, SMCs rather than macrophages are responsible for MMP production that is critical for aneurysmal lesion development. These SMCs exhibit proinflammatory behavior.

  6. Preliminary study of small scale solar test cells for solar thermal evaluation of building components

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez, G. [CIEMAT, Renewable Energy Dept., Madrid (Spain)]|[CENIDET, Mechanical Engineering Dept., Cuernavaca, Morelos (Mexico); Jimenez, M.J.; Heras, M.R. [CIEMAT, Renewable Energy Dept., Madrid (Spain)

    2004-07-01

    This paper presents a preliminary study to validate small scale solar test cells for thermal evaluation of building components such as windows and roofs. The description and performance of the scale test cells are described. The validation of the thermal performance was made with the real test cell Passys indirectly by applying the classical averaging method that was initially used for the Passys cells to determine overall heat loss coefficient, UA, and the solar heat gain, gA. The use of this methodology was selected, as a first approach, to evaluate the viability of the study of scale test cells. Our preliminary results indicate that some percentage differences were high for some tests. Therefore, it is necessary to increase the period of time of the measurements of the scale test cells, in order to use dynamic system methods to reduce the percentage differences of UA and gA. (orig.)

  7. [Effect of lidamycin on mitochondria initiated apoptotic pathway in human cancer cells].

    Science.gov (United States)

    Qiu, Qiang; Wang, Zhen; Jiang, Jian-ming; Li, Dian-dong

    2007-02-01

    Although enediyne antibiotic lidamycin ( LDM) is a potent inducer of apoptosis, the underlying mechanisms of its apoptotic functions remain to be explored. Here, we aim to elucidate its possible mechanisms in mitochondria initiated apoptotic pathway involved in human BEL-7402 and MCF-7 cells. Cytochrome c released from mitchondria to cytosol fraction was detected by Western blotting. p53 and Bax, Bcl-2 expressions were detected by Western blotting and RT-PCR. MTT assay was used to detect cytotoxicity of LDM with or without caspase inhibitor z-VAD-fmk. After the BEL-7402 cells were exposed to 0. 1 micromol x L(-1) LDM within 6 h, the increase of cytochrome c in the cytosol and decrease in the mitochondria were observed when compared with untreated cells. The expression of Bax, an important proapoptotic member of the Bcl-2 family, increased gradually in the BEL-7402 cells after exposure to LDM of 0. 1 micromol x L (-1) for 2, 6, and 9 h, separately, while Bcl-2 increased at 2 and 6 h, and decreased at 9 h after LDM treatment. Enhanced protein expressions were parallel with respective increased mRNA level for Bax only, but not p53. Caspase inhibitor may inhibit partially the killing effects induced by LDM. Therefore we conclude that the rapid activation of mitochondrial pathway induced by LDM in tumor cells might contribute to its highly potent cytotoxicities. PMID:17518039

  8. Nanoporous metals for biodegradable implants: Initial bone mesenchymal stem cell adhesion and degradation behavior.

    Science.gov (United States)

    Heiden, Michael; Huang, Sabrina; Nauman, Eric; Johnson, David; Stanciu, Lia

    2016-07-01

    Nanostructured Fe-Mn and Fe-Mn-Zn metal scaffolds were generated through a well-controlled selective leaching process in order to fulfill the growing demand for adjustable degradation rates and improved cellular response of resorbable materials. Mouse bone marrow mesenchymal stem cells (D1 ORL UVA) were seeded onto eleven, carefully chosen nanoporous surfaces for 24 h in vitro. Using a combination of fluorescence microscopy, scanning electron microscopy (SEM), and an MTS assay, it was discovered that scaffolds with nanoscale roughened surfaces had increased cell attachment by up to 123% compared to polished smooth Fe-Mn surfaces. Significant cell spreading and construction of cell multilayers were also apparent after 24 h, suggesting better adhesion. Additionally, static electrochemical polarization experiments revealed an improvement of up to 26% in the actual rate of biodegradation for Fe-Mn surface-modified materials. However, any residual concentration of zinc after leaching was shown to slightly increase corrosion resistance. The results demonstrate that selectively leached, nanostructured Fe-Mn surfaces have the potential of being tailored to a diverse set of transient implant scenarios, while also effectively boosting overall biocompatibility, initial cell attachment, and degradation rate. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1747-1758, 2016. PMID:26990484

  9. Conditioned medium from human bone marrow stromal cells attenuates initial inflammatory reactions in dental pulp tissue

    OpenAIRE

    Al-Sharabi, Niyaz; Mustafa, Manal; Xue, Ying; Ueda, Minoru; Mustafa, Kamal; Fristad, Inge

    2016-01-01

    Aim. To evaluate the effect of MSC-conditioned medium (CM) on the secretion of pro- and anti-inflammatory cytokines from dental pulp cells (hDPC) in vitro, and on the gene expression in vivo after replantation of rat molars. Materials and methods. hDPC were cultured in CM for 24 h, and the concentration of interleukin IL-10, IL-4, IL-6, and IL-8, regulated on activation, normal T Cell expressed and secreted (RANTES), and prostaglandin E2 (PGE2) in the media were measured by multiplex ass...

  10. Initial evaluation of thyroid nodules by primary care physicians and internal medicine residents

    Directory of Open Access Journals (Sweden)

    Celeste C. L. Quianzon

    2015-04-01

    Full Text Available Objective: The article studied the knowledge and practice patterns of primary care providers and internal medicine residents in their initial evaluation of thyroid nodules and determined whether their practice is in accordance with published guidelines by the American Thyroid Association and American Association of Clinical Endocrinologists. Method: A survey was distributed to primary care physicians (PCPs and internal medicine residents at a community hospital in Baltimore and a chart review was conducted at the Diabetes and Endocrine Center in the same hospital. Results: A total of 47 physicians (70% responded to the survey, 16 PCPs and 33 residents. Most responders (96% will always obtain a TSH, and of these, 21% of PCP and 25% of residents will obtain a TSH without any other laboratory work-up. Fifty percent of the physicians (PCP, 75%; resident, 39% will always obtain a thyroid ultrasound (p=0.043. Most physicians (97% will refer for a fine-needle aspiration (FNA biopsy of a nodule >1 cm. Sixty-two percent of the physicians will not put a euthyroid patient on levothyroxine suppression therapy. Many physicians (48% are not aware of the AACE and ATA thyroid nodule guidelines. Most physicians (65% have not read the guidelines. Of the 113 charts reviewed, TSH was obtained alone in 40% and with other laboratory tests in 74%. Thyroid ultrasound was done in 67%. Only one patient was on levothyroxine for levothyroxine suppression therapy. Discussion: Although many physicians were not aware of the guidelines, and a small number of physicians have read them, many PCP and residents responded in concordance with the guidelines in obtaining TSH, an ultrasound, performing FNA biopsy, and not providing levothyroxine suppressive therapy in euthyroid patients. No differences were found between the responses of PCP and residents except for obtaining an ultrasound. Chart review data also showed that majority of tests ordered for non-toxic thyroid nodule

  11. Co-Transcriptomes of Initial Interactions In Vitro between Streptococcus Pneumoniae and Human Pleural Mesothelial Cells.

    Directory of Open Access Journals (Sweden)

    Claire J Heath

    Full Text Available Streptococcus pneumoniae (Spn is a major causative organism of empyema, an inflammatory condition occurring in the pleural sac. In this study, we used human and Spn cDNA microarrays to characterize the transcriptional responses occurring during initial contact between Spn and a human pleural mesothelial cell line (PMC in vitro. Using stringent filtering criteria, 42 and 23 Spn genes were up-and down-regulated respectively. In particular, genes encoding factors potentially involved in metabolic processes and Spn adherence to eukaryotic cells were up-regulated e.g. glnQ, glnA, aliA, psaB, lytB and nox. After Spn initial contact, 870 human genes were differentially regulated and the largest numbers of significant gene expression changes were found in canonical pathways for eukaryotic initiation factor 2 signaling (60 genes out of 171, oxidative phosphorylation (32/103, mitochondrial dysfunction (37/164, eIF4 and p70S6K signaling (28/142, mTOR signaling (27/182, NRF2-mediated oxidative stress response (20/177, epithelial adherens junction remodeling (11/66 and ubiquitination (22/254. The cellular response appeared to be directed towards host cell survival and defense. Spn did not activate NF-kB or phosphorylate p38 MAPK or induce cytokine production from PMC. Moreover, Spn infection of TNF-α pre-stimulated PMC inhibited production of IL-6 and IL-8 secretion by >50% (p<0.01. In summary, this descriptive study provides datasets and a platform for examining further the molecular mechanisms underlying the pathogenesis of empyema.

  12. Decreased origin usage and initiation of DNA replication in haploinsufficient HCT116 Ku80+/- cells.

    Science.gov (United States)

    Sibani, Sahar; Price, Gerald B; Zannis-Hadjopoulos, Maria

    2005-08-01

    One of the functions of the abundant heterodimeric nuclear protein, Ku (Ku70/Ku80), is its involvement in the initiation of DNA replication through its ability to bind to chromosomal replication origins in a sequence-specific and cell cycle dependent manner. Here, using HCT116 Ku80+/- cells, the effect of Ku80 deficiency on cell cycle progression and origin activation was examined. Western blot analyses revealed a 75% and 36% decrease in the nuclear expression of Ku80 and Ku70, respectively. This was concomitant with a 33% and 40% decrease in chromatin binding of both proteins, respectively. Cell cycle analysis of asynchronous and late G1 synchronized Ku80+/- cells revealed a prolonged G1 phase. Furthermore, these Ku-deficient cells had a 4.5-, 3.4- and 4.3-fold decrease in nascent strand DNA abundance at the lamin B2, beta-globin and c-myc replication origins, respectively. Chromatin immunoprecipitation (ChIP) assays showed that the association of Ku80 with the lamin B2, beta-globin and c-myc origins was decreased by 1.5-, 2.3- and 2.5-fold, respectively, whereas that of Ku70 was similarly decreased (by 2.1-, 1.5- and 1.7-fold, respectively) in Ku80+/- cells. The results indicate that a deficiency of Ku80 resulted in a prolonged G1 phase, as well as decreased Ku binding to and activation of origins of DNA replication. PMID:16014376

  13. Interleukin 1 beta initially sensitizes and subsequently protects murine intestinal stem cells exposed to photon radiation

    International Nuclear Information System (INIS)

    Interleukin 1 (IL-1) has been shown to prevent early bone marrow-related death following total-body irradiation, by protecting hematopoietic stem cells and speeding marrow repopulation. This study assesses the effect of IL-1 on the radiation response of the intestinal mucosal stem cell, a nonhematopoietic normal cell relevant to clinical radiation therapy. As observed with bone marrow, administration of human recombinant IL-1 beta (4 micrograms/kg) to C3H/Km mice 20 h prior to total-body irradiation modestly protected duodenal crypt cells. In contrast to bone marrow, IL-1 given 4 or 8 h before radiation sensitized intestinal crypt cells. IL-1 exposure did not substantially alter the slope of the crypt cell survival curve but did affect the shoulder: the X-ray survival curve was offset to the right by 1.01 +/- 0.06 Gy when IL-1 was given 20 h earlier and by 1.28 +/- 0.08 Gy to the left at the 4-h interval. Protection was greatest when IL-1 was administered 20 h before irradiation, but minimal effects persisted as long as 7 days after a single injection. The magnitude of radioprotection at 20 h or of radiosensitization at 4 h increased rapidly as IL-1 dose increased from 0 to 4 micrograms/kg. However, doses ranging from 10 to 100 micrograms/kg produced no further difference in radiation response. Animals treated with saline or IL-1 had similar core temperatures from 4 to 24 h after administration, suggesting that thermal changes were not responsible for either sensitization or protection. Mice irradiated 20 h after IL-1 had significantly greater crypt cell survival than saline-treated irradiated controls at all assay times, which ranged from 54 to 126 h following irradiation. The intervals to maximum crypt depopulation and initiation of repopulation were identical in both saline- and IL-1-treated groups

  14. Autophagy mediates survival of pancreatic tumour-initiating cells in a hypoxic microenvironment.

    Science.gov (United States)

    Rausch, Vanessa; Liu, Li; Apel, Anja; Rettig, Theresa; Gladkich, Jury; Labsch, Sabrina; Kallifatidis, Georgios; Kaczorowski, Adam; Groth, Ariane; Gross, Wolfgang; Gebhard, Martha M; Schemmer, Peter; Werner, Jens; Salnikov, Alexei V; Zentgraf, Hanswalter; Büchler, Markus W; Herr, Ingrid

    2012-07-01

    Involvement of dysregulated autophagy in cancer growth and progression has been shown in different tumour entities, including pancreatic ductal adenocarcinoma (PDA). PDA is an extremely aggressive tumour characterized by a small population of highly therapy-resistant cancer stem cells (CSCs) capable of self-renewal and migration. We examined whether autophagy might be involved in the survival of CSCs despite nutrition and oxygen deprivation typical for the hypoxic tumour microenvironment of PDA. Immunohistochemistry revealed that markers for hypoxia, CSCs and autophagy are co-expressed in patient-derived tissue of PDA. Hypoxia starvation (H/S) enhanced clonogenic survival and migration of established pancreatic cancer cells with stem-like properties (CSC(high)), while pancreatic tumour cells with fewer stem cell markers (CSC(low)) did not survive these conditions. Electron microscopy revealed more advanced autophagic vesicles in CSC(high) cells, which exhibited higher expression of autophagy-related genes under normoxic conditions and relative to CSC(low) cells, as found by RT-PCR and western blot analysis. LC3 was already fully converted to the active LC3-II form in both cell lines, as evaluated by western blot and detection of accumulated GFP-LC3 protein by fluorescence microscopy. H/S increased formation of autophagic and acid vesicles, as well as expression of autophagy-related genes, to a higher extent in CSC(high) cells. Modulation of autophagy by inhibitors and activators resensitized CSC(high) to apoptosis and diminished clonogenicity, spheroid formation, expression of CSC-related genes, migratory activity and tumourigenicity in mice. Our data suggest that enhanced autophagy levels may enable survival of CSC(high) cells under H/S. Interference with autophagy-activating or -inhibiting drugs disturbs the fine-tuned physiological balance of enhanced autophagy in CSC and switches survival signalling to suicide. PMID:22262369

  15. New-generation taxoid SB-T-1214 inhibits stem cell-related gene expression in 3D cancer spheroids induced by purified colon tumor-initiating cells

    Directory of Open Access Journals (Sweden)

    Rowehl Rebecca A

    2010-07-01

    Full Text Available Abstract Background Growing evidence suggests that the majority of tumors are organized hierarchically, comprising a population of tumor-initiating, or cancer stem cells (CSCs responsible for tumor development, maintenance and resistance to drugs. Previously we have shown that the CD133high/CD44high fraction of colon cancer cells is different from their bulk counterparts at the functional, morphological and genomic levels. In contrast to the majority of colon cancer cells expressing moderate levels of CD133, CD44 and CD166, cells with a high combined expression of CD133 and CD44 possessed several characteristic stem cell features, including profound self-renewal capacity in vivo and in vitro, and the ability to give rise to different cell phenotypes. The present study was undertaken for two aims: a to determine stem cell-related genomic characteristics of floating 3D multicellular spheroids induced by CD133high/CD44high colon cancer cells; and b to evaluate CSC-specific alterations induced by new-generation taxoid SB-T-1214. Results Selected CSC phenotype was isolated from three independent invasive colon cancer cell lines, HCT116, HT29 and DLD-1. A stem cell-specific PCR array assay (SABiosciences revealed that colonospheres induced by purified CD133high/CD44high expressing cells display profound up-regulation of stem cell-related genes in comparison with their bulk counterparts. The FACS analysis has shown that the 3D colonospheres contained some minority cell populations with high levels of expression of Oct4, Sox2, Nanog and c-Myc, which are essential for stem cell pluripotency and self-renewal. Single administration of the SB-T-1214 at concentration 100 nM-1 μM for 48 hr not only induced growth inhibition and apoptotic cell death in these three types of colon cancer spheroids in 3D culture, but also mediated massive inhibition of the stem cell-related genes and significant down-regulation of the pluripotency gene expression. PCR array and

  16. Initial presentation of CNS-restricted acute lymphoblastic B cell leukaemia as peripheral polyneuropathy.

    Science.gov (United States)

    Piovezani Ramos, Guilherme; Villasboas Bisneto, Jose C; Chen, Dong; Pardanani, Animesh

    2016-01-01

    We report a case of a 58-year-old woman who presented with a 1-month course of progressive lower and upper extremity weakness in addition to binocular diplopia. Diagnostic lumbar puncture revealed atypical lymphoid cells with 28% blasts. Immunophenotype was consistent with B cell acute lymphoblastic leukaemia (B-ALL). Further work up showed no systemic involvement but extensive thoracolumbar-sacral leptomeningeal disease. The patient was treated with several courses of intrathecal and systemic chemotherapy followed by craniospinal irradiation for consolidation. There was initial steady improvement in neurological symptoms and leptomeningeal disease, the latter being ascertained through radiological studies and cerebrospinal fluid examination. After 10 months of response, the patient relapsed with central nervous system (CNS) and systemic disease. B-ALL is a rare precursor lymphoid neoplasm that generally presents with systemic disease. While CNS involvement is not uncommon, isolated involvement of this compartment without systemic disease is exceedingly rare. PMID:27095809

  17. Fuel Cell Electric Vehicle Evaluation; NREL (National Renewable Energy Laboratory)

    Energy Technology Data Exchange (ETDEWEB)

    Kurtz, Jennifer; Sprik, Sam; Ainscough, Chris; Saur, Genevieve

    2015-06-10

    This presentation provides a summary of NREL's FY15 fuel cell electric vehicle evaluation project activities and accomplishments. It was presented at the U.S. Department of Energy Hydrogen and Fuel Cells Program 2015 Annual Merit Review and Peer Evaluation Meeting on June 10, 2015, in Arlington, Virginia.

  18. Chromium(VI) stimulates Fyn to initiate innate immune gene induction in human airway epithelial cells

    Science.gov (United States)

    Nemec, Antonia A.; Zubritsky, Lindsey M.; Barchowsky, Aaron

    2009-01-01

    Mechanisms for pathogenic metal signaling in airway injury or disease promotion are poorly understood. It is widely believed that one mechanism for pathogenic and possible carcinogenic effects of inhaled chromium (Cr(VI)) is inhibition of inducible gene transactivation. However, we recently reported that Cr(VI) inhibition of Sp1-dependent transactivation required signal transducer and activator of transcription 1 (STAT1)-dependent expression of an inhibitory protein in airway epithelium. Thus, Cr(VI) exposures can induce genes and we hypothesized this induction resulted from Cr(VI) signaling through an innate immune-like STAT1-dependent pathway initiated by Fyn. Exposure of human airway epithelial (BEAS-2B) cells to Cr(VI) selectively transactivated STAT-responsive interferon-stimulated response element (ISRE) and induced ISRE-driven transactivation of interferon regulatory factor 7 (IRF7), without affecting the gamma interferon-activated site (GAS)-driven IRF1 expression. Cr(VI)-induced IRF7 was absent or greatly reduced in cells that lacked STAT1, were treated with the Src family kinase inhibitor, PP2, or lacked Fyn. Expressing Fyn, but not Src, in mouse embryonic fibroblasts cells null for Src, Yes, and Fyn restored Cr(VI)-stimulated STAT1 tyrosine phosphorylation and IRF7 expression. Finally, shRNA knockdown of Fyn in BEAS-2B cells prevented Cr(VI)-activated STAT1 transactivation of IRF7. These data support a novel mechanism through which Cr(VI) stimulates Fyn to initiate interferon-like signaling for STAT1-dependent gene transactivation. PMID:19994902

  19. Evaluation of wireless sensor networks (WSNs) for remote wetland monitoring: design and initial results.

    Science.gov (United States)

    Watras, Carl J; Morrow, Michael; Morrison, Ken; Scannell, Sean; Yaziciaglu, Steve; Read, Jordan S; Hu, Yu-Hen; Hanson, Paul C; Kratz, Tim

    2014-02-01

    Here, we describe and evaluate two low-power wireless sensor networks (WSNs) designed to remotely monitor wetland hydrochemical dynamics over time scales ranging from minutes to decades. Each WSN (one student-built and one commercial) has multiple nodes to monitor water level, precipitation, evapotranspiration, temperature, and major solutes at user-defined time intervals. Both WSNs can be configured to report data in near real time via the internet. Based on deployments in two isolated wetlands, we report highly resolved water budgets, transient reversals of flow path, rates of transpiration from peatlands and the dynamics of chromophoric-dissolved organic matter and bulk ionic solutes (specific conductivity)-all on daily or subdaily time scales. Initial results indicate that direct precipitation and evapotranspiration dominate the hydrologic budget of both study wetlands, despite their relatively flat geomorphology and proximity to elevated uplands. Rates of transpiration from peatland sites were typically greater than evaporation from open waters but were more challenging to integrate spatially. Due to the high specific yield of peat, the hydrologic gradient between peatland and open water varied with precipitation events and intervening periods of dry out. The resultant flow path reversals implied that the flux of solutes across the riparian boundary varied over daily time scales. We conclude that WSNs can be deployed in remote wetland-dominated ecosystems at relatively low cost to assess the hydrochemical impacts of weather, climate, and other perturbations. PMID:24046241

  20. The initial evaluation in the working process of occupational therapists in the mental health system

    Directory of Open Access Journals (Sweden)

    Alana de Paiva Nogueira Fornereto Gozzi

    2013-12-01

    Full Text Available : In the field of mental health, Occupational Therapy uses different references in practice development. It is important to observe how occupational therapists in the mental health system assess users’ demands on their work scenarios. In this research, we aimed to study the assessment process of occupational therapists in different services of the mental health system. A descriptive cross-sectional case study was conducted using a qualitative approach. Data were obtained through interviews with occupational therapists integrated to the mental health services of a specific region. The region studied belongs to a Regional Health Department in the state of São Paulo. The thematic analysis method was applied to the data collected allowing the dentification of categories of analysis. The results obtained from one of these categories (the assessment process of occupational therapists showed that most of the professionals interviewed do perform the initial evaluation. This assessment was carried out informally in every case employing tools built by the professionals themselves during their own practices. In addition, patients with chronic mental illnesses are usually admitted in the Occupational Therapy services studied. These characteristics, obtained from active professionals, are useful in the creation of technical criteria for users’ admission in Occupational Therapy mental health treatment.

  1. Extended Plate and Beam Wall System: Concept Investigation and Initial Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Wiehagen, J. [Partnership for Home Innovation, Upper Marlboro, MD (United States); Kochkin, V. [Partnership for Home Innovation, Upper Marlboro, MD (United States)

    2015-08-01

    A new and innovative High-R wall design, referred to as the Extended Plate & Beam (EP&B), is under development. The EP&B system uniquely integrates foam sheathing insulation with wall framing such that wood structural panels are installed exterior of the foam sheathing, enabling the use of standard practices for installation of drainage plane, windows and doors, claddings, cavity insulation, and the standard exterior foam sheathing installation approach prone to damage of the foam during transportation of prefabricated wall panels. As part of the ongoing work, the EP&B wall system concept has undergone structural verification testing and has been positively vetted by a group of industry stakeholders. Having passed these initial milestone markers, the advanced wall system design has been analyzed to assess cost implications relative to other advanced wall systems, undergone design assessment to develop construction details, and has been evaluated to develop representative prescriptive requirements for the building code. This report summarizes the assessment steps conducted to-date and provides details of the concept development.

  2. Initial evaluation of bone ingrowth into a novel porous titanium coating.

    Science.gov (United States)

    Wazen, Rima M; Lefebvre, Louis-Philippe; Baril, Eric; Nanci, Antonio

    2010-07-01

    Porous metals (sintered beads and meshes) have been used for many years for different orthopedic applications. Metal foams have been recently developed. These foams have the advantage of being more porous than the traditional coatings. Their high porosity provides more space for bone ingrowth and mechanical interlocking and presents more surface for implant-bone contact. The objective of this study was to evaluate in vivo bone ingrowth into Ti implants covered with a novel Ti foam coating. This foam contains 50% in volume of interconnected pores and a higher surface area compared to dense Ti. Both coated implants and dense Ti controls were placed transcortically in the rat tibia. The animals were sacrificed at 2 weeks after implantation, and the amount of bone in the implants was determined using backscattered electron imaging and X-ray microtomography. Already at this time interval, the pores within the Ti foam showed 97.7% bone filling, and the bone-implant contact area was significantly increased compared to dense Ti controls. These initial results indicate that this novel Ti foam is biocompatible, has the capacity to sustain bone formation, and can potentially improve osseointegration. PMID:20336725

  3. Design, synthesis, and initial evaluation of D-glyceraldehyde crosslinked gelatin-hydroxyapatite as a potential bone graft substitute material

    Science.gov (United States)

    Florschutz, Anthony Vatroslav

    Utilization of bone grafts for the treatment of skeletal pathology is a common practice in orthopaedic, craniomaxillofacial, dental, and plastic surgery. Autogenous bone graft is the established archetype but has disadvantages including donor site morbidity, limited supply, and prolonging operative time. In order to avoid these and other issues, bone graft substitute materials are becoming increasingly prevalent among surgeons for reconstructing skeletal defects and arthrodesis applications. Bone graft substitutes are biomaterials, biologics, and guided tissue/bone regenerative devices that can be used alone or in combinations as supplements or alternatives to autogenous bone graft. There is a growing interest and trend to specialize graft substitutes for specific indications and although there is good rationale for this indication-specific approach, the development and utility of a more universal bone graft substitute may provide a better answer for patients and surgeons. The aim of the present research focuses on the design, synthesis, and initial evaluation of D-glyceraldehyde crosslinked gelatin-hydroxyapatite composites for potential use as a bone graft substitutes. After initial establishment of rational material design, gelatinhydroxyapatite scaffolds were fabricated with different gelatin:hydroxyapatite ratios and crosslinking concentrations. The synthesized scaffolds were subsequently evaluated on the basis of their swelling behavior, porosity, density, percent composition, mechanical properties, and morphology and further assessed with respect to cell-biomaterial interaction and biomineralization in vitro. Although none of the materials achieved mechanical properties suitable for structural graft applications, a reproducible material design and synthesis was achieved with properties recognized to facilitate bone formation. Select scaffold formulations as well as a subset of scaffolds loaded with recombinant human bone morphogenetic protein-2 were

  4. Evaluation of the Ethiopian Millennium Rural Initiative: impact on mortality and cost-effectiveness.

    Directory of Open Access Journals (Sweden)

    Leslie A Curry

    Full Text Available MAIN OBJECTIVE: Few studies have examined the long-term, impact of large-scale interventions to strengthen primary care services for women and children in rural, low-income settings. We evaluated the impact of the Ethiopian Millennium Rural Initiative (EMRI, an 18-month systems-based intervention to improve the performance of 30 primary health care units in rural areas of Ethiopia. METHODS: We assessed the impact of EMRI on maternal and child survival using The Lives Saved Tool (LiST, Demography (DemProj and AIDS Impact Model (AIM tools in Spectrum software, inputting monthly data on 6 indicators 1 antenatal coverage (ANC, 2 skilled birth attendance coverage (SBA, 3 post-natal coverage (PNC, 4 HIV testing during ANC, 5 measles vaccination coverage, and 6 pentavalent 3 vaccination coverages. We calculated a cost-benefit ratio of the EMRI program including lives saved during implementation and lives saved during implementation and 5 year follow-up. RESULTS: A total of 134 lives (all children were estimated to have been saved due to the EMRI interventions during the 18-month intervention in 30 health centers and their catchment areas, with an estimated additional 852 lives (820 children and 2 adults saved during the 5-year post-EMRI period. For the 18-month intervention period, EMRI cost $37,313 per life saved ($42,366 per life if evaluation costs are included. Calculated over the 18-month intervention plus 5 years post-intervention, EMRI cost $5,875 per life saved ($6,671 per life if evaluation costs are included. The cost effectiveness of EMRI improves substantially if the performance achieved during the 18 months of the EMRI intervention is sustained for 5 years. Scaling up EMRI to operate for 5 years across the 4 major regions of Ethiopia could save as many as 34,908 lives. SIGNIFICANCE: A systems-based approach to improving primary care in low-income settings can have transformational impact on lives saved and be cost-effective.

  5. Heterogeneity of leukemia-initiating capacity of chronic myelogenous leukemia stem cells.

    Science.gov (United States)

    Zhang, Bin; Li, Ling; Ho, Yinwei; Li, Min; Marcucci, Guido; Tong, Wei; Bhatia, Ravi

    2016-03-01

    Chronic myelogenous leukemia (CML) results from transformation of a long-term hematopoietic stem cell (LTHSC) by expression of the BCR-ABL fusion gene. However, BCR-ABL-expressing LTHSCs are heterogeneous in their capacity as leukemic stem cells (LSCs). Although discrepancies in proliferative, self-renewal, and differentiation properties of normal LTHSCs are being increasingly recognized, the mechanisms underlying heterogeneity of leukemic LTHSCs are poorly understood. Using a CML mouse model, we identified gene expression differences between leukemic and nonleukemic LTHSCs. Expression of the thrombopoietin (THPO) receptor MPL was elevated in leukemic LTHSC populations. Compared with LTHSCs with low MPL expression, LTHSCs with high MPL expression showed enhanced JAK/STAT signaling and proliferation in response to THPO in vitro and increased leukemogenic capacity in vivo. Although both G0 and S phase subpopulations were increased in LTHSCs with high MPL expression, LSC capacity was restricted to quiescent cells. Inhibition of MPL expression in CML LTHSCs reduced THPO-induced JAK/STAT signaling and leukemogenic potential. These same phenotypes were also present in LTHSCs from patients with CML, and patient LTHSCs with high MPL expression had reduced sensitivity to BCR-ABL tyrosine kinase inhibitor treatment but increased sensitivity to JAK inhibitors. Together, our studies identify MPL expression levels as a key determinant of heterogeneous leukemia-initiating capacity and drug sensitivity of CML LTHSCs and suggest that high MPL-expressing CML stem cells are potential targets for therapy. PMID:26878174

  6. A new method for determination of most likely landslide initiation points and the evaluation of digital terrain model scale in terrain stability mapping

    Directory of Open Access Journals (Sweden)

    P. Tarolli

    2006-01-01

    Full Text Available This paper introduces a new approach for determining the most likely initiation points for landslides from potential instability mapped using a terrain stability model. This approach identifies the location with critical stability index from a terrain stability model on each downslope path from ridge to valley. Any measure of terrain stability may be used with this approach, which here is illustrated using results from SINMAP, and from simply taking slope as an index of potential instability. The relative density of most likely landslide initiation points within and outside mapped landslide scars provides a way to evaluate the effectiveness of a terrain stability measure, even when mapped landslide scars include run out zones, rather than just initiation locations. This relative density was used to evaluate the utility of high resolution terrain data derived from airborne laser altimetry (LIDAR for a small basin located in the Northeastern Region of Italy. Digital Terrain Models were derived from the LIDAR data for a range of grid cell sizes (from 2 to 50 m. We found appreciable differences between the density of most likely landslide initiation points within and outside mapped landslides with ratios as large as three or more with the highest ratios for a digital terrain model grid cell size of 10 m. This leads to two conclusions: (1 The relative density from a most likely landslide initiation point approach is useful for quantifying the effectiveness of a terrain stability map when mapped landslides do not or can not differentiate between initiation, runout, and depositional areas; and (2 in this study area, where landslides occurred in complexes that were sometimes more than 100 m wide, a digital terrain model scale of 10 m is optimal. Digital terrain model scales larger than 10 m result in loss of resolution that degrades the results, while for digital terrain model scales smaller than 10 m the physical processes responsible for triggering

  7. Regulation of eukaryotic initiation factor 4AII by MyoD during murine myogenic cell differentiation.

    Directory of Open Access Journals (Sweden)

    Gabriela Galicia-Vázquez

    Full Text Available Gene expression during muscle cell differentiation is tightly regulated at multiple levels, including translation initiation. The PI3K/mTOR signalling pathway exerts control over protein synthesis by regulating assembly of eukaryotic initiation factor (eIF 4F, a heterotrimeric complex that stimulates recruitment of ribosomes to mRNA templates. One of the subunits of eIF4F, eIF4A, supplies essential helicase function during this phase of translation. The presence of two cellular eIF4A isoforms, eIF4AI and eIF4AII, has long thought to impart equivalent functions to eIF4F. However, recent experiments have alluded to distinct activities between them. Herein, we characterize distinct regulatory mechanisms between the eIF4A isoforms during muscle cell differentiation. We find that eIF4AI levels decrease during differentiation whereas eIF4AII levels increase during myofiber formation in a MyoD-dependent manner. This study characterizes a previously undefined mechanism for eIF4AII regulation in differentiation and highlights functional differences between eIF4AI and eIF4AII. Finally, RNAi-mediated alterations in eIF4AI and eIF4AII levels indicate that the myogenic process can tolerate short term reductions in eIF4AI or eIF4AII levels, but not both.

  8. Nitric Oxide Inhibits Hetero-adhesion of Cancer Cells to Endothelial Cells: Restraining Circulating Tumor Cells from Initiating Metastatic Cascade

    Science.gov (United States)

    Lu, Yusheng; Yu, Ting; Liang, Haiyan; Wang, Jichuang; Xie, Jingjing; Shao, Jingwei; Gao, Yu; Yu, Suhong; Chen, Shuming; Wang, Lie; Jia, Lee

    2014-03-01

    Adhesion of circulating tumor cells (CTCs) to vascular endothelial bed becomes a crucial starting point in metastatic cascade. We hypothesized that nitric oxide (NO) may prevent cancer metastasis from happening by its direct vasodilation and inhibition of cell adhesion molecules (CAMs). Here we show that S-nitrosocaptopril (CAP-NO, a typical NO donor) produced direct vasorelaxation that can be antagonized by typical NO scavenger hemoglobin and guanylate cyclase inhibitor. Cytokines significantly stimulated production of typical CAMs by the highly-purified human umbilical vein endothelial cells (HUVECs). CAP-NO inhibited expression of the stimulated CAMs (particularly VCAM-1) and the resultant hetero-adhesion of human colorectal cancer cells HT-29 to the HUVECs in a concentration-dependent manner. The same concentration of CAP-NO, however, did not significantly affect cell viability, cell cycle and mitochondrial membrane potential of HT-29, thus excluding the possibility that inhibition of the hetero-adhesion was caused by cytotoxicity by CAP-NO on HT-29. Hemoglobin reversed the inhibition of CAP-NO on both the hetero-adhesion between HT-29 and HUVECs and VCAM-1 expression. These data demonstrate that CAP-NO, by directly releasing NO, produces vasorelaxation and interferes with hetero-adhesion of cancer cells to vascular endothelium via down-regulating expression of CAMs. The study highlights the importance of NO in cancer metastatic prevention.

  9. {sup 18}F-labeled RGD peptide: initial evaluation for imaging brain tumor angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chen Xiaoyuan; Park, Ryan; Shahinian, Anthony H.; Tohme, Michel; Khankaldyyan, Vazgen; Bozorgzadeh, Mohammed H.; Bading, James R.; Moats, Rex; Laug, Walter E.; Conti, Peter S. E-mail: pconti@usc.edu

    2004-02-01

    Brain tumors are highly angiogenesis dependent. The cell adhesion receptor integrin {alpha}{sub v}{beta}{sub 3} is overexpressed in glioma and activated endothelial cells and plays an important role in brain tumor growth, spread and angiogenesis. Suitably labeled {alpha}{sub v}{beta}{sub 3}-integrin antagonists may therefore be useful for imaging brain tumor associated angiogenesis. Cyclic RGD peptide c(RGDyK) was labeled with {sup 18}F via N-succinimidyl-4-[{sup 18}F]fluorobenzoate through the side-chain {epsilon}-amino group of the lysine residue. The radiotracer was evaluated in vivo for its tumor targeting efficacy and pharmacokinetics in subcutaneously implanted U87MG and orthotopically implanted U251T glioblastoma nude mouse models by means of microPET, quantitative autoradiography and direct tissue sampling. The N-4-[{sup 18}F]fluorobenzoyl-RGD ([{sup 18}F]FB-RGD) was produced in less than 2 h with 20-25% decay-corrected yields and specific activity of 230 GBq/{mu}mol at end of synthesis. The tracer showed very rapid blood clearance and both hepatobiliary and renal excretion. Tumor-to-muscle uptake ratio at 30 min was approximately 5 in the subcutaneous U87MG tumor model. MicroPET imaging with the orthotopic U251T brain tumor model revealed very high tumor-to-brain ratio, with virtually no uptake in the normal brain. Successful blocking of tumor uptake of [{sup 18}F]FB-RGD in the presence of excess amount of c(RGDyK) revealed receptor specific activity accumulation. Hence, N-4-[{sup 18}F]fluorobenzoyl labeled cyclic RGD peptide [{sup 18}F]FB-RGD is a potential tracer for imaging {alpha}{sub v}{beta}{sub 3}-integrin positive tumors in brain and other anatomic locations.

  10. Small cell carcinoma of vulva. Curative multimodal treatment in face of resistance to initial standard chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Eckert, Franziska; Bamberg, Michael; Mueller, Arndt-Christian [Dept. of Radiooncology, Eberhard Karls Univ. of Tuebingen (Germany); Fehm, Tanja [Gynecologic Clinic, Eberhard Karls Univ. of Tuebingen (Germany)

    2010-09-15

    Background and Purpose: Extrapulmonary small cell carcinoma (EPSCC) is a rare disease, which has a slightly better prognosis than small cell lung cancer, but still dismal. Gynecologic small cell malignancies tend to show a better survival than similar histologies of other regions. However, of five reported cases of vulvar manifestation only one patient was disease-free at the time of publication with limited follow-up. Case Report: The authors describe a case of locally advanced small cell vulva carcinoma infiltrating the anal sphincter and urethra with spread to inguinal lymph nodes treated by radiochemotherapy and regional hyperthermia. After three cycles of carboplatin/etoposide, computed tomography and magnetic resonance imaging indicated only little regressive transformations but overall stable disease. Surgical options were excluded. Therefore, curative radiotherapy to a total dose of > 65 Gy to macroscopic tumor, chemotherapy with cisplatin weekly, and regional hyperthermia were performed. Acute severe toxicity was limited to skin reactions. Despite the disadvantageous situation with inguinal lymph node metastases and chemoresistance, the multimodal therapy yielded a 5-year disease-free survival. Conclusion: Thus, the trimodal regimen of radiochemotherapy plus regional hyperthermia offered a curative chance in spite of resistance to the standard chemotherapy for irresectable, locally advanced small cell carcinoma of the vulva. Therefore, this approach merits further evaluation for limited disease of EPSCC. (orig.)

  11. Small cell carcinoma of vulva. Curative multimodal treatment in face of resistance to initial standard chemotherapy

    International Nuclear Information System (INIS)

    Background and Purpose: Extrapulmonary small cell carcinoma (EPSCC) is a rare disease, which has a slightly better prognosis than small cell lung cancer, but still dismal. Gynecologic small cell malignancies tend to show a better survival than similar histologies of other regions. However, of five reported cases of vulvar manifestation only one patient was disease-free at the time of publication with limited follow-up. Case Report: The authors describe a case of locally advanced small cell vulva carcinoma infiltrating the anal sphincter and urethra with spread to inguinal lymph nodes treated by radiochemotherapy and regional hyperthermia. After three cycles of carboplatin/etoposide, computed tomography and magnetic resonance imaging indicated only little regressive transformations but overall stable disease. Surgical options were excluded. Therefore, curative radiotherapy to a total dose of > 65 Gy to macroscopic tumor, chemotherapy with cisplatin weekly, and regional hyperthermia were performed. Acute severe toxicity was limited to skin reactions. Despite the disadvantageous situation with inguinal lymph node metastases and chemoresistance, the multimodal therapy yielded a 5-year disease-free survival. Conclusion: Thus, the trimodal regimen of radiochemotherapy plus regional hyperthermia offered a curative chance in spite of resistance to the standard chemotherapy for irresectable, locally advanced small cell carcinoma of the vulva. Therefore, this approach merits further evaluation for limited disease of EPSCC. (orig.)

  12. The effectiveness of active travel initiatives in Irish provincial towns: an evaluation of a quasi-experimental natural experiment

    OpenAIRE

    Lambe, Barry

    2015-01-01

    Ireland is a car dependent country with low levels of active travel and also low levels of total physical activity. There is a paucity of studies, internationally, that have evaluated active travel initiatives in a real world setting. This thesis contributes new knowledge to the evidence base on the implementation, effectiveness and design of active travel initiatives at the community level and their impact on physical activity. This thesis is comprised of a series of quasi-experimental de...

  13. Initiation of Antiretroviral Therapy (ART) at Different Stages of HIV-1 Disease Is Not Associated with the Proportion of Exhausted CD8+ T Cells

    DEFF Research Database (Denmark)

    Jensen, Sanne Skov; Fomsgaard, Anders; Larsen, Tine Kochendorf; Tingstedt, Jeanette Linnea; Gerstoft, Jan; Kronborg, Gitte; Pedersen, Court; Karlsson, Ingrid

    2015-01-01

    cells expressing the inhibitory markers PD-1, 2B4 and CD160 was lower in ART-treated individuals compared with ART-naïve individuals and similar to the frequency in HIV-uninfected controls. The expression of the three markers was similarly independent of when therapy was initiated. Individuals treated......CD8+ T cell-restricted immunity is important in the control of HIV-1 infection, but continued immune activation results in CD8+ T cell dysfunction. Early initiation of antiretroviral treatment (ART) and the duration of ART have been associated with immune reconstitution. Here, we evaluated whether...... restoration of CD8+ T cell function in HIV-1-infected individuals was dependent on early initiation of ART. HIV-specific CD107a, IFNγ, IL-2, TNFα and MIP-1β expression by CD8+ T cells and the frequency of CD8+ T cells expressing PD-1, 2B4 and CD160 were measured by flow cytometry. The frequency of CD8+ T...

  14. High expression of CD109 antigen regulates the phenotype of cancer stem-like cells/cancer-initiating cells in the novel epithelioid sarcoma cell line ESX and is related to poor prognosis of soft tissue sarcoma.

    Directory of Open Access Journals (Sweden)

    Makoto Emori

    Full Text Available Epithelioid sarcoma (ES is a relatively rare, highly malignant soft tissue sarcoma. The mainstay of treatment is resection or amputation. Currently other therapeutic options available for this disease are limited. Therefore, a novel therapeutic option needs to be developed. In the present study, we established a new human ES cell line (ESX and analyzed the characteristics of its cancer stem-like cells/cancer-initiating cells (CSCs/CICs based on ALDH1 activity. We demonstrated that a subpopulation of ESX cells with high ALDH1 activity (ALDH(high cells correlated with enhanced clonogenic ability, sphere-formation ability, and invasiveness in vitro and showed higher tumorigenicity in vivo. Next, using gene expression profiling, we identified CD109, a GPI-anchored protein upregulated in the ALDH(high cells. CD109 mRNA was highly expressed in various sarcoma cell lines, but weakly expressed in normal adult tissues. CD109-positive cells in ESX predominantly formed spheres in culture, whereas siCD109 reduced ALDH1 expression and inhibited the cell proliferation in vitro. Subsequently, we evaluated the expression of CD109 protein in 80 clinical specimens of soft tissue sarcoma. We found a strong correlation between CD109 protein expression and the prognosis (P = 0.009. In conclusion, CD109 might be a CSC/CIC marker in epithelioid sarcoma. Moreover, CD109 is a promising prognostic biomarker and a molecular target of cancer therapy for sarcomas including ES.

  15. TISs-ST: a web server to evaluate polymorphic translation initiation sites and their reflections on the secretory targets

    Directory of Open Access Journals (Sweden)

    Menossi Marcelo

    2007-05-01

    Full Text Available Abstract Background The nucleotide sequence flanking the translation initiation codon (start codon context affects the translational efficiency of eukaryotic mRNAs, and may indicate the presence of an alternative translation initiation site (TIS to produce proteins with different properties. Multi-targeting may reflect the translational variability of these other protein forms. In this paper we present a web server that performs computations to investigate the usage of alternative translation initiation sites for the synthesis of new protein variants that might have different functions. Results An efficient web-based tool entitled TISs-ST (Translation Initiation Sites and Secretory Targets evaluates putative translation initiation sites and indicates the prediction of a signal peptide of the protein encoded from this site. The TISs-ST web server is freely available to both academic and commercial users and can be accessed at http://ipe.cbmeg.unicamp.br/pub/TISs-ST. Conclusion The program can be used to evaluate alternative translation initiation site consensus with user-specified sequences, based on their composition or on many position weight matrix models. TISs-ST provides analytical and visualization tools for evaluating the periodic frequency, the consensus pattern and the total information content of a sequence data set. A search option allows for the identification of signal peptides from predicted proteins using the PrediSi software.

  16. Development, implementation and evaluation of a peer review of teaching (PRoT) initiative in nursing education.

    Science.gov (United States)

    Mager, Diana R; Kazer, Meredith W; Conelius, Jaclyn; Shea, Joyce; Lippman, Doris T; Torosyan, Roben; Nantz, Kathryn

    2014-01-01

    For many years, an area of research in higher education has been emerging around the development and implementation of fair and effective peer evaluation programs. Recently, a new body of knowledge has developed regarding the development and implementation of fair and effective peer evaluation programs resulting in formative and summative evaluations. The purpose of this article is to describe the development, implementation, and evaluation of a peer review of teaching (PRoT) program for nursing faculty, initiated at one small comprehensive university in the northeastern United States. Pairs of nursing faculty evaluated each other's teaching, syllabi, and course materials after collaborating in a pre-evaluation conference to discuss goals of the classroom visit. Qualitative data gathered in post project focus groups revealed that faculty found their modified PRoT process to be a mutually beneficial experience that was more useful, flexible and collegial, and less stressful than their previous evaluation process. PMID:24893326

  17. Short communication: Initial evidence supporting existence of potential rumen epidermal stem and progenitor cells.

    Science.gov (United States)

    Yohe, T T; Tucker, H L M; Parsons, C L M; Geiger, A J; Akers, R M; Daniels, K M

    2016-09-01

    The bovine rumen epidermis is a keratinized multilayered tissue that experiences persistent cell turnover. Because of this constant cell turnover, epidermal stem cells and their slightly more differentiated daughter cells, epidermal progenitor cells, must exist in the stratum basale of rumen epidermis. To date, these 2 epidermal cell populations and any unique cellular markers they may possess remain completely uncharacterized in the bovine rumen. An important first step in this new research area is the demonstration of the relative abundance and existence of markers for these cells in rumen tissue. A related second step is to document rumen epidermal proliferative responses to an extrinsic signal such as nutrient concentration within the rumen. The objectives of this experiment were to evaluate the extrinsic effect of diet on (1) gene expression of 6 potential rumen epidermal stem or progenitor cell markers and (2) rumen epidermal cell proliferation within the stratum basale. Twelve preweaned Holstein heifers were fed either a restricted diet (R) or an enhanced diet (EH). Animals on R received a milk replacer (MR) diet fed at 0.44kg of powder dry matter (DM)/d (20.9% crude protein, 29.8% fat, DM basis) and EH received MR at 1.08kg of powder dry matter/d (28.9% crude protein, 26.2% fat, DM basis). All calves had access to a 20% crude protein starter and were weaned during wk 7 of the experiment. Lifetime DM intake was 0.73kg of DM/calf per day for R (5.88 Mcal of net energy/calf per day) and 1.26kg of DM/calf per day for EH (10.68 Mcal of net energy/calf per day). Twenty-four hours before slaughter heifers received an intravenous dose of 5-bromo-2'-deoxyuridine to label proliferating cells. Heifers were slaughtered at 8 wk of age, and rumen samples from the ventral sac region were obtained and stored in RNA preservative and processed for routine histology. Quantitative real-time reverse transcriptase PCR was used to analyze relative abundance of genes. Candidate

  18. The Early College High School Initiative: An Overview of Five Evaluation Years

    Science.gov (United States)

    Berger, Andrea; Adelman, Nancy; Cole, Susan

    2010-01-01

    In 2002, the Bill & Melinda Gates Foundation started the Early College High School Initiative (ECHSI). Through this initiative, more than 200 Early College Schools (ECSs) opened by fall 2009. All of the schools aim to provide underserved students access to college classes while in high school. This article will provide an overview of the first 6…

  19. Cuyahoga County Early Childhood Initiative Evaluation: Phase II Final Report. Executive Summary

    Science.gov (United States)

    Fischer, Rob; Coulton, Claudia

    2005-01-01

    Since mid-1999, a bold initiative has been underway in Cuyahoga County, Ohio, to improve the well-being of the youngest members of the greater Cleveland community. A community-wide initiative targeting children from birth through age five and their families was launched in July 1999, and in the following 5 years demonstrated substantial success in…

  20. Monitoring and Evaluation During the Bulldozer Initiative - 50 Investment Climate Reforms in 150 Days

    OpenAIRE

    Herzberg, Benjamin

    2007-01-01

    The bulldozer initiative in Bosnia and Herzegovina is an example of a public-private dialogue that successfully overcame the lack of political will and capacity at the government level through a bottom-up approach. The initiative mobilized the local business community to "bulldoze" business environment barriers by identifying concrete legislative changes and advocating for their implementa...

  1. Calculation of a Reactivity Initiated Accident with a 3D Cell-by-Cell Method: Application of the SAPHYR System to a Rod Ejection Accident in TMI1

    International Nuclear Information System (INIS)

    The 3D method for neutronic calculations of a Reactivity-Initiated Accident (RIA) in a Pressurized Water Reactor (PWR) tends now to replace the former 2D-1D evaluations. In the frame of a search of adequate penalties to apply to this new type of transient modeling, sensitivity studies on the geometrical description accuracy, on the type of physical phenomena modeled and on the values of the key physical parameters are currently undertaken by the IPSN and the CEA. 3D core neutronic calculations with a homogeneous and a heterogeneous (cell by cell) assembly modeling were compared. The influence of the axial neutronic calculation meshing was studied. As far as thermal-hydraulics is concerned, cross flow effects were measured by a comparison of 3D and 1D core FLICA4 models (each assembly being represented by one thermal-hydraulic channel). A more accurate feedback modeling was also studied by adjusting the thermal-hydraulic calculation meshes to the neutronic ones (four thermal-hydraulic channels per assembly). All these tests showed first that the power transient can be noticeably affected by the scale of the core physical modeling and by the type of physical phenomena taken into account (moderator feedback effects, core cross flows..). They also have highlighted that, for each studied model parameter, a preliminary search for the 'envelope transient' is necessary to be sure to evaluate its maximum impact on power transients. (authors)

  2. Preliminary safety evaluation, based on initial site investigation data. Planning document

    International Nuclear Information System (INIS)

    This report is a planning document for the preliminary safety evaluations (PSE) to be carried out at the end of the initial stage of SKBs ongoing site investigations for a deep repository for spent nuclear fuel. The main purposes of the evaluations are to determine whether earlier judgements of the suitability of the candidate area for a deep repository with respect to long-term safety holds up in the light of borehole data and to provide feed-back to continued site investigations and site specific repository design. The preliminary safety evaluations will be carried out by a safety assessment group, based on a site model, being part of a site description, provided by a site modelling group and a repository layout within that model suggested by a repository engineering group. The site model contains the geometric features of the site as well as properties of the host rock. Several alternative interpretations of the site data will likely be suggested. Also the biosphere is included in the site model. A first task for the PSE will be to compare the rock properties described in the site model to previously established criteria for a suitable host rock. This report gives an example of such a comparison. In order to provide more detailed feedback, a number of thermal, hydrological, mechanical and chemical analyses of the site will also be included in the evaluation. The selection of analyses is derived from the set of geosphere and biosphere analyses preliminarily planned for the comprehensive safety assessment named SR-SITE, which will be based on a complete site investigation. The selection is dictated primarily by the expected feedback to continued site investigations and by the availability of data after the PSE. The repository engineering group will consider several safety related factors in suggesting a repository layout: Thermal calculations will be made to determine a minimum distance between canisters avoiding canister surface temperatures above 100 deg C

  3. Evaluation of the global lung function initiative 2012 reference values for spirometry in a Swedish population sample

    OpenAIRE

    Backman, Helena; Lindberg, Anne; Sovijarvi, Anssi; Larsson, Kjell; Lundbäck, Bo; Rönmark, Eva

    2015-01-01

    Background The Global Lung Function Initiative 2012 (GLI) reference values are currently endorsed by several respiratory societies but evaluations of applicability for adults resident in European countries are lacking. The aim of this study was to evaluate if the GLI reference values are appropriate for an adult Caucasian Swedish population. Methods During 2008–2013, clinical examinations including spirometry were performed on general population samples in northern Sweden, in which 501 health...

  4. Diffusion is capable of translating anisotropic apoptosis initiation into a homogeneous execution of cell death.

    LENUS (Irish Health Repository)

    Huber, Heinrich J

    2010-01-01

    ABSTRACT: BACKGROUND: Apoptosis is an essential cell death process throughout the entire life span of all metazoans and its deregulation in humans has been implicated in many proliferative and degenerative diseases. Mitochondrial outer membrane permeabilisation (MOMP) and activation of effector caspases are key processes during apoptosis signalling. MOMP can be subject to spatial coordination in human cancer cells, resulting in intracellular waves of cytochrome-c release. To investigate the consequences of these spatial anisotropies in mitochondrial permeabilisation on subsequent effector caspase activation, we devised a mathematical reaction-diffusion model building on a set of partial differential equations. RESULTS: Reaction-diffusion modelling suggested that even if strong spatial anisotropies existed during mitochondrial cytochrome c release, these would be eliminated by free diffusion of the cytosolic proteins that instantiate the apoptosis execution network. Experimentally, rapid sampling of mitochondrial permeabilisation and effector caspase activity in individual HeLa cervical cancer cells confirmed predictions of the reaction-diffusion model and demonstrated that the signalling network of apoptosis execution could efficiently translate spatial anisotropies in mitochondrial permeabilisation into a homogeneous effector caspase response throughout the cytosol. Further systems modelling suggested that a more than 10,000-fold impaired diffusivity would be required to maintain spatial anisotropies as observed during mitochondrial permeabilisation until the time effector caspases become activated. CONCLUSIONS: Multi-protein diffusion efficiently contributes to eliminating spatial asynchronies which are present during the initiation of apoptosis execution and thereby ensures homogeneous apoptosis execution throughout the entire cell body. For previously reported biological scenarios in which effector caspase activity was shown to be targeted selectively to

  5. Initial rates of DNA incision in UV-irradiated human cells

    International Nuclear Information System (INIS)

    Following UV-irradiation and in the presence of inhibitors of DNA synthesis (hydroxyurea and 1-β-D-arabinofuranosylcytosine) human cells accumulate strand breaks in their DNA - as a result of enzymic incision without subsequent rejoining. We have developed a sensitive procedure which makes stringent use of these inhibitors so as to maximize the frequency of breaks detected after low levels of UV (0.25 - 10 Jm-2) and to permit analysis of the kinetics of break accumulation over short intervals after irradiation (up to 90 min). Since the rate of accumulation of breaks declines quickly with time of incubation (not simply as a consequence of substrate depletion), we have calculated initial rate constants by extrapolating to zero time for a range of UV doses (i.e. different substrate concentrations). (orig./AJ)

  6. Red Blood Cell Transfusion Independence Following the Initiation of Iron Chelation Therapy in Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Maha A. Badawi

    2010-01-01

    Full Text Available Iron chelation therapy is often used to treat iron overload in patients requiring transfusion of red blood cells (RBC. A 76-year-old man with MDS type refractory cytopenia with multilineage dysplasia, intermediate-1 IPSS risk, was referred when he became transfusion dependent. He declined infusional chelation but subsequently accepted oral therapy. Following the initiation of chelation, RBC transfusion requirement ceased and he remained transfusion independent over 40 months later. Over the same time course, ferritin levels decreased but did not normalize. There have been eighteen other MDS patients reported showing improvement in hemoglobin level with iron chelation; nine became transfusion independent, nine had decreased transfusion requirements, and some showed improved trilineage myelopoiesis. The clinical features of these patients are summarized and possible mechanisms for such an effect of iron chelation on cytopenias are discussed.

  7. Initial evaluation of airborne water vapour measurements by the IAGOS-GHG CRDS system

    Science.gov (United States)

    Filges, Annette; Gerbig, Christoph; Smit, Herman G. J.; Krämer, Martina; Spelten, Nicole

    2013-04-01

    Accurate and reliable airborne measurements of water vapour are still a challenge. Presently, no airborne humidity sensor exists that covers the entire range of water vapour content between the surface and the upper troposphere/lower stratosphere (UT/LS) region with sufficient accuracy and time resolution. Nevertheless , these data are a pre-requisite to study the underlying processes in the chemistry and physics of the atmosphere. The DENCHAR project (Development and Evaluation of Novel Compact Hygrometer for Airborne Research) addresses this deficit by developing and characterizing novel or improved compact airborne hygrometers for different airborne applications within EUFAR (European Facility for Airborne Research). As part of the DENCHAR inter-comparison campaign in Hohn (Germany), 23 May - 1 June 2011, a commercial gas analyzer (G2401-m, Picarro Inc.,US), based on cavity ring-down spectroscopy (CRDS), was installed on a Learjet to measure water vapour, CO2, CH4 and CO. The CRDS components are identical to those chosen for integration aboard commercial airliner within IAGOS (In-service Aircraft for a Global Observing System). Thus the campaign allowed for the initial assessment validation of the long-term IAGOS H2O measurements by CRDS against reference instruments with a long performance record (FISH, the Fast In-situ Stratospheric Hygrometer, and CR2 frostpoint hygrometer, both research centre Juelich). The inlet system, a one meter long 1/8" FEP-tube connected to a Rosemount TAT housing (model 102BX, deiced) installed on a window plate of the aircraft, was designed to eliminate sampling of larger aerosols, ice particles, and water droplets, and provides about 90% of ram-pressure. In combination with a lowered sample flow of 0.1 slpm (corresponding to a 4 second response time), this ensured a fully controlled sample pressure in the cavity of 140 torr throughout an aircraft altitude operating range up to 12.5 km without the need of an upstream sampling pump

  8. Synthesis of 2-18F-fluoroisonicotinic acid hydrazide and initial biological evaluation

    International Nuclear Information System (INIS)

    Isonicotinic acid hydrazide (isonizide) is one of the most effective agents in tuberculosis therapy. This agent rapidly permeates the bacterial cell membrane via passive diffusion. The central nervous system tuberculosis is being observed in patients who are intravenous drug abusers, with AIDS and AIDS-related complex. Therefore, radiopharmaceuticals for diagnosis of tuberculosis may become important. Very few attempts have been made to develop isonicotinic acid and derivatives for the same application. As part of an on-going research effort to develop radiotracers for fluorination of proteins and peptides via prosthetic groups approach, we have synthesized ethyl 2-[18F]-fluoroisonicotinate and 2-[18F]-fluoroisonicotinic acid hydrazide. The synthetic approach starts from treatment of ethyl-2-(trimethylammonium)-isonicotinate precursor using no-carrier-added radiofluoride produced by the 18O(p,n)18F nuclear reaction on 18O-enriched (95 %) water and Kryptofix 222 as nucleophilic catalyst in anhydrous acetonitrile at 1000C, gave ethyl 2-[18F]-fluoroisonicotinate in greater than 90% radiochemical yield (decay corrected) within two minutes reaction time. The ether extract of fluorinated ethylester evaporated and residue was re-dissolved in ethanol and treated with hydrazine for 15 minutes in boiling water to obtain 2-[18F]-fluoroisonicotinic acid hydrazide in excellent radiochemical yield. The overall radiochemical yield was greater that 70% with total synthesis time of approximately one hour. This synthetic approach hold considerable promise as a rapid and simple method for fluorination of radiopharmaceuticals of high radiochemical yield. Biological evaluation was performed in normal mice. The data obtained shown that the lungs appear to retain some activity that someone may presume that such radiotracer maybe useful in detection of tuberculosis

  9. 78 FR 27219 - Dominion Bridgeport Fuel Cell, LLC; Supplemental Notice That Initial Market-Based Rate Filing...

    Science.gov (United States)

    2013-05-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Dominion Bridgeport Fuel Cell, LLC; Supplemental Notice That Initial Market... in the above-referenced proceeding of Dominion Bridgeport Fuel Cell, LLC's application for...

  10. 40 CFR 63.7941 - How do I conduct a performance test, design evaluation, or other type of initial compliance...

    Science.gov (United States)

    2010-07-01

    ..., design evaluation, or other type of initial compliance demonstration? (a) You must conduct a performance... device is used), as determined by Method 2 of 40 CFR part 60, appendix A, dscm/h; n = Number of organic... determined by Method 18 of 40 CFR part 60, appendix A; MWi = Molecular weight of organic compound i in...

  11. Impact and Process Evaluation of the U.S. Department of Energy's Wind Powering America Initiative

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-05-01

    This report presents an evaluation of the impacts and processes of the former Wind Powering America(WPA) initiative sponsored by the U.S. Department of Energy (DOE). WPA has an underlying goal of dramatically increasing the use of wind energy in the U.S.

  12. Evaluation of the LiveWell@School Food Initiative Shows Increases in Scratch Cooking and Improvement in Nutritional Content

    Science.gov (United States)

    Schober, Daniel J.; Carpenter, Leah; Currie, Venita; Yaroch, Amy L.

    2016-01-01

    Background: The purpose of this evaluation was to examine the effects of the LiveWell@School Food Initiative (LW@SFI), a Colorado-based childhood obesity prevention program that partners with school districts to enable them to serve more scratch cooked foods through culinary training, action planning, and equipment grants. Methods: This evaluation…

  13. Evaluations of environmental effect on micro crack initiation and propagation by surface observations of fatigue specimens

    International Nuclear Information System (INIS)

    Fatigue life of nuclear facilities tends to be decreased by the influence of reactor coolant, which is called environmental effect. The effect accelerates crack growth rate but the influence for crack initiation is not clarified. This study intends to discuss the environmental effect in crack initiation. The crack length and the number of cracks are measured from the investigation of fatigue test specimens in reactor coolant and air. The behavior of crack initiation is revealed from the measurement of number of cracks, crack sizes and fatigue life. From this study, environmental effect of reactor coolant is considered to influence crack initiation and increase the number of micro crack. It is also estimated that the coalescence of cracks influences the acceleration of crack growth. (author)

  14. Uncertainty Evaluation of Weibull Estimators through Monte Carlo Simulation: Applications for Crack Initiation Testing

    Directory of Open Access Journals (Sweden)

    Jae Phil Park

    2016-06-01

    Full Text Available The typical experimental procedure for testing stress corrosion cracking initiation involves an interval-censored reliability test. Based on these test results, the parameters of a Weibull distribution, which is a widely accepted crack initiation model, can be estimated using maximum likelihood estimation or median rank regression. However, it is difficult to determine the appropriate number of test specimens and censoring intervals required to obtain sufficiently accurate Weibull estimators. In this study, we compare maximum likelihood estimation and median rank regression using a Monte Carlo simulation to examine the effects of the total number of specimens, test duration, censoring interval, and shape parameters of the true Weibull distribution on the estimator uncertainty. Finally, we provide the quantitative uncertainties of both Weibull estimators, compare them with the true Weibull parameters, and suggest proper experimental conditions for developing a probabilistic crack initiation model through crack initiation tests.

  15. Evaluating the performance of vehicular platoon control under different network topologies of initial states

    Science.gov (United States)

    Li, Yongfu; Li, Kezhi; Zheng, Taixiong; Hu, Xiangdong; Feng, Huizong; Li, Yinguo

    2016-05-01

    This study proposes a feedback-based platoon control protocol for connected autonomous vehicles (CAVs) under different network topologies of initial states. In particularly, algebraic graph theory is used to describe the network topology. Then, the leader-follower approach is used to model the interactions between CAVs. In addition, feedback-based protocol is designed to control the platoon considering the longitudinal and lateral gaps simultaneously as well as different network topologies. The stability and consensus of the vehicular platoon is analyzed using the Lyapunov technique. Effects of different network topologies of initial states on convergence time and robustness of platoon control are investigated. Results from numerical experiments demonstrate the effectiveness of the proposed protocol with respect to the position and velocity consensus in terms of the convergence time and robustness. Also, the findings of this study illustrate the convergence time of the control protocol is associated with the initial states, while the robustness is not affected by the initial states significantly.

  16. Evaluation of Dynamic Models of Distillation Columns with Emphasis on the Initial Response

    Directory of Open Access Journals (Sweden)

    Bernd Wittgens

    2000-04-01

    Full Text Available The flow dynamics (tray hydraulics are of key importance for the initial dynamic response of distillation columns. The most important parameters are the liquid holdup, the liquid hydraulic time constant and the vapor constant representing the initial effect of a change in vapor flow on liquid flow. In the paper we present methods for determining these parameters experimentally, and compare the results with estimates from available correlations such as the Francis Weir formula.

  17. Evaluating Open Source Software for Use in Library Initiatives: A Case Study Involving Electronic Publishing

    Science.gov (United States)

    Samuels, Ruth Gallegos; Griffy, Henry

    2012-01-01

    This article discusses best practices for evaluating open source software for use in library projects, based on the authors' experience evaluating electronic publishing solutions. First, it presents a brief review of the literature, emphasizing the need to evaluate open source solutions carefully in order to minimize Total Cost of Ownership. Next,…

  18. Mechanisms of triplex DNA-mediated inhibition of transcription initiation in cells.

    Science.gov (United States)

    Jain, Aklank; Magistri, Marco; Napoli, Sara; Carbone, Giuseppina M; Catapano, Carlo V

    2010-03-01

    Triplex-forming oligonucleotides (TFOs) are attractive tools to control gene expression at the transcriptional level. This anti-gene approach has proven to be successful in various experimental settings. However, the mechanisms leading to transcriptional repression in cells have not been fully investigated yet. Here, we examined the consequence of triplex DNA formation on the binding of transcriptional activators, co-activators and RNA Polymerase II to the ets2 gene promoter using chromatin immunoprecipitation assays. The triplex target sequence was located approximately 40-bp upstream of the transcription start site (TSS) and overlapped an Sp1 binding site relevant for ets2 transcription. We found that the ets2-TFO prevented binding of Sp1, TAF(II)130 and TAF(II)250 to the ets2 promoter, while binding of RNA polymerase II and TBP were not affected. The effects were both sequence and target specific, since the TFO had no effect on the c-myc promoter and a mutated ets2 promoter construct. Thus, triplex DNA formation near a TSS leads to formation of a non-functional pre-initiation complex (PIC) by blocking binding of transcriptional activators and co-activator molecules. This is the first direct demonstration of interference with PIC assembly at the TSS by oligonucleotide-triplex DNA formation in cells. PMID:20045441

  19. Evaluation of the metabolic fate of munitions material (TNT & RDX) in plant systems. Initial assessment of plant DNA mutation spectra as a biomarker

    Energy Technology Data Exchange (ETDEWEB)

    Leung, F.; Cataldo, D.A.; Fellows, R.J.; Jarrell, A.E.; Harvey, S.D.

    1995-09-01

    Munitions material can enter the environment as a result of manufacturing activities and field usage. Predictor methodologies, or biomarkers would enhance evaluation of environmental impacts. The goal of this exploratory study deoxyribonucleic acid (DNA) mutation frequency as a biomarker for munitions exposure. The approach e resolution of an effective repetitive sequence probe for the identification of characteristic mutations, and (2) the development of a testing media [a clonal cell line of carrot (Daucus carota) spension cells]. Commercially available probes demonstrated marginal resolution therefore a low-C{sub o}t library was then constructed. Three colonies from the low-C{sub o}t DNA library were screened and the DNA isolates sequenced. A suspension culture of carrot (Daucus carota) was developed. A mutation spectra experiment was initiated at a 10-mg TNT/L exposure concentration with the attempt to clone over 1500 single TNT-exposed cells. Over the following six months greater than 98% of the initially isolated cells were unable to survive and produce micro calluses. The remaining calli were too few to be statistically significant and the experiment was terminated. The biomarker concept itself remains to be disproved, but the need for large numbers of uniform clones to differentiate true mutations suggest that more direct techniques using whole tissues need to be developed.

  20. Mapping of ESE-1 subdomains required to initiate mammary epithelial cell transformation via a cytoplasmic mechanism

    Directory of Open Access Journals (Sweden)

    Tentler John J

    2011-08-01

    Full Text Available Abstract Background The ETS family transcription factor ESE-1 is often overexpressed in human breast cancer. ESE-1 initiates transformation of MCF-12A cells via a non-transcriptional, cytoplasmic process that is mediated by a unique 40-amino acid serine and aspartic acid rich (SAR subdomain, whereas, ESE-1's nuclear transcriptional property is required to maintain the transformed phenotype of MCF7, ZR-75-1 and T47D breast cancer cells. Results To map the minimal functional nuclear localization (NLS and nuclear export (NES signals, we fused in-frame putative NLS and NES motifs between GFP and the SAR domain. Using these GFP constructs as reporters of subcellular localization, we mapped a single NLS to six basic amino acids (242HGKRRR247 in the AT-hook and two CRM1-dependent NES motifs, one to the pointed domain (NES1: 102LCNCALEELRL112 and another to the DNA binding domain (DBD, (NES2: 275LWEFIRDILI284. Moreover, analysis of a putative NLS located in the DBD (316GQKKKNSN323 by a similar GFP-SAR reporter or by internal deletion of the DBD, revealed this sequence to lack NLS activity. To assess the role of NES2 in regulating ESE-1 subcellular localization and subsequent transformation potency, we site-specifically mutagenized NES2, within full-length GFP-ESE-1 and GFP-NES2-SAR reporter constructs. These studies show that site-specific mutation of NES2 completely abrogates ESE-1 transforming activity. Furthermore, we show that exclusive cytoplasmic targeting of the SAR domain is sufficient to initiate transformation, and we report that an intact SAR domain is required, since block mutagenesis reveals that an intact SAR domain is necessary to maintain its full transforming potency. Finally, using a monoclonal antibody targeting the SAR domain, we demonstrate that the SAR domain contains a region accessible for protein - protein interactions. Conclusions These data highlight that ESE-1 contains NLS and NES signals that play a critical role in

  1. Identification of a novel subpopulation of tumor-initiating cells from gemcitabine-resistant pancreatic ductal adenocarcinoma patients.

    Directory of Open Access Journals (Sweden)

    Kazuya Shimizu

    Full Text Available Pancreatic ductal adenocarcinoma is highly resistant to systemic chemotherapy. Although there are many reports using pancreatic cancer cells derived from patients who did not receive chemotherapy, characteristics of pancreatic cancer cells from chemotherapy-resistant patients remain unclear. In this study, we set out to establish a cancer cell line in disseminated cancer cells derived from gemcitabine-resistant pancreatic ductal adenocarcinoma patients. By use of in vitro co-culture system with stromal cells, we established a novel pancreatic tumor-initiating cell line. The cell line required its direct interaction with stromal cells for its in vitro clonogenic growth and passaging. Their direct interaction induced basal lamina-like extracellular matrix formation that maintained colony formation. The cell line expressed CD133 protein, which expression level changed autonomously and by culture conditions. These results demonstrated that there were novel pancreatic tumor-initiating cells that required direct interactions with stromal cells for their in vitro cultivation in gemcitabine-resistant pancreatic ductal adenocarcinoma. This cell line would help to develop novel therapies that enhance effects of gemcitabine or novel anti-cancer drugs.

  2. Evaluation of the effects of initial conditions on transients in PUMA

    International Nuclear Information System (INIS)

    Major differences between the SBWR and the currently operating BWRs include the use of passive gravity-driven systems in the SBWR for emergency cooling of the vessel and containment. In order to investigate the phenomena expected during a Loss of Coolant Accident (LOCA), NRC has sponsored an integral scaled-test facility, called Purdue, University Multidimensional Integral Test Assembly (PUMA). The facility models all the major safety-related components of SBWR. Two PUMA initialization calculations were performed to assist the Purdue University in establishing test initialization procedures. Both calculations were based on the initial conditions obtained from SBWR LOCA simulation. In the base case, a complete separation between vapor and liquid was assumed, with all the water in the lower part of the Reactor Pressure Vessel (RPV) and all the vapor above it. In the sensitivity case, the water inventory was distributed in the vessel in the same way as in the SBWR at 1.034 MPa, which is the initial pressure for PUMA facility. Purdue University plans to initialize the PUMA tests as in the base case. The sensitivity calculation is performed to provide assurance that this mode of initialization is adequate. It also provides information on possible differences in the progress of transients. The conditions outside of the vessel were identical for both cases prior to initiation of the accident. The paper will discuss the differences in the early part of the transient. The conclusion from this study will also apply to many integral facilities which simulate the reactor transients from the middle of the transient

  3. Cotinine inhibits the pro-inflammatory response initiated by multiple cell surface Toll-like receptors in monocytic THP cells

    Directory of Open Access Journals (Sweden)

    Bagaitkar Juhi

    2012-11-01

    Full Text Available Abstract Background The primary, stable metabolite of nicotine [(S-3-(1-methyl-2-pyrrolidinyl pyridine] in humans is cotinine [(S-1-methyl-5-(3-pyridinyl-2-pyrrolidinone]. We have previously shown that cotinine exposure induces convergence and amplification of the GSK3β-dependent PI3 kinase and cholinergic anti-inflammatory systems. The consequence is reduced pro-inflammatory cytokine secretion by human monocytes responding to bacteria or LPS, a TLR4 agonist. Findings Here we show that cotinine-induced inflammatory suppression may not be restricted to individual Toll-like receptors (TLRs. Indeed, in monocytic cells, cotinine suppresses the cytokine production that is normally resultant upon agonist-specific engagement of all of the major surface exposed TLRs (TLR 2/1; 2/6; 4 and 5, although the degree of suppression varies by TLR. Conclusions These results provide further mechanistic insight into the increased susceptibility to multiple bacterial infections known to occur in smokers. They also establish THP-1 cells as a potentially suitable model with which to study the influence of tobacco components and metabolites on TLR-initiated inflammatory events.

  4. Connecticut Transit (CTTRANSIT) Fuel Cell Transit Bus: Preliminary Evaluation Results

    Energy Technology Data Exchange (ETDEWEB)

    Chandler, K.; Eudy, L.

    2008-10-01

    This report provides preliminary results from a National Renewable Energy Laboratory evaluation of a protoptye fuel cell transit bus operating at Connecticut Transit in Hartford. Included are descriptions of the planned fuel cell bus demonstration and equipment; early results and agency experience are also provided.

  5. Inhibition of carcinoma formation and of vascular invasion in grafts of radiation-initiated thyroid clonogens by unirradiated thyroid cells

    International Nuclear Information System (INIS)

    Quantitative transplantation techniques have been employed to study radiogenic cancer initiation frequency and cell interactions during promotion/progression in grafted clonogenic rat thyroid epithelial cells. The graft recipients were surgically thyroidectomized. Radiogenic initiation is a common cellular event; one of ∼ 32 surviving 5-Gy-irradiated thyroid clonogens gave rise to cancer in grafts initially containing ∼ 11 clonogens per transplantation site. The efficiency of promotion/progression is inversely related to grafted irradiated cell number. As the number of transplanted surviving irradiated clonogens was increased progressively from ∼ 11 to ∼ 720 clonogens per graft site, the carcinoma frequency per grafted clonogen progressively decreased to one per ∼ 920. Addition of unirradiated thyroid cells to the transplant inocula further suppressed promotion/progression of radiation-initiated thyroid clonogens. Furthermore, the probability of vascular invasion, a reflection of metastatic potential in carcinomas which arose from irradiated grafted thyroid clonogens, was reduced by addition of unirradiated thyroid cells to the transplant inocula. Assays of thyroid stimulating hormone (TSH) titers in the sera of thyroidectomized rats 44 weeks after transplantation of clonogenic thyroid cells indicate that the suppression of neoplastic promotion/progression observed with increased numbers of cells per graft site is due at least in part to feed-back inhibition of TSH production by thyroid hormone of graft origin. (author)

  6. 1,25-dihydroxyvitamin D3 conditioned CD11c+ dendritic cells are effective initiators of CNS autoimmune disease

    Directory of Open Access Journals (Sweden)

    Dario eBesusso

    2015-11-01

    Full Text Available Dendritic cells (DC play a crucial role in regulating T cell activation. Due to their capacity to shape the immune response, tolerogenic DC have been used to treat autoimmune diseases. In this study we examined whether 1,25 dihydroxyvitamin D3 conditioned bone marrow derived DC (VitD-BMDC were able to limit the development of autoimmune pathology in experimental autoimmune encephalomyelitis (EAE. We found that VitD-BMDC had lower expression of MHC class II and co-stimulatory molecules and were less effective at priming autoreactive T cells in-vitro. Using our recently described BMDC driven model of EAE, we demonstrated that VitD-BMDC had a significantly reduced ability to initiate EAE. We found that the impaired ability of VitD-BMDC to initiate EAE was not due to T cell tolerisation. Instead, we discovered that the addition of 1,25(OH2D3 to BMDC cultures resulted in a significant reduction in the proportion of CD11c+ cells. Purified CD11c+VitD-BMDC were significantly less effective at priming T cells in-vitro yet were similarly capable of initiating EAE as vehicle treated CD11c+BMDC. This study demonstrates that in-vitro assays of DC function can be a poor predictor of in-vivo behaviour and that CD11c+VitD-BMDC are highly effective initiators of an autopathogenic T cell response.

  7. Integrating Assessment and Evaluation Into Partnership Initiatives: Lessons From the Community Partnerships for Older Adults.

    Science.gov (United States)

    Giunta, Nancy; Thomas, M Lori

    2015-08-01

    Communities nationwide have formed cross-sector partnerships to face the needs of an aging population, particularly for the purpose of improving long-term supportive service systems. Research is limited on how evaluation strategies are incorporated into partnership work, especially in the field of aging. This retrospective qualitative study reviewed administrative and key informant interview data to examine how 15 community partnerships (CPs) within the Community Partnerships for Older Adults (CPFOA) national program incorporated evaluation into their work. The four overarching lessons drawn from our inquiry suggest that effective CPs: (a) incorporate both formative and summative methods into evaluation, (b) use and develop the knowledge and skills of its members, (c) support flexible and creative evaluation methods and strategies, and (d) use internal and external resources to support evaluation efforts, particularly with nontraditional partners. There is a need for continued research to capture the methodological complexity of partnership evaluation. PMID:24652885

  8. Paneth Cell-Rich Regions Separated by a Cluster of Lgr5+ Cells Initiate Crypt Fission in the Intestinal Stem Cell Niche.

    Science.gov (United States)

    Langlands, Alistair J; Almet, Axel A; Appleton, Paul L; Newton, Ian P; Osborne, James M; Näthke, Inke S

    2016-06-01

    The crypts of the intestinal epithelium house the stem cells that ensure the continual renewal of the epithelial cells that line the intestinal tract. Crypt number increases by a process called crypt fission, the division of a single crypt into two daughter crypts. Fission drives normal tissue growth and maintenance. Correspondingly, it becomes less frequent in adulthood. Importantly, fission is reactivated to drive adenoma growth. The mechanisms governing fission are poorly understood. However, only by knowing how normal fission operates can cancer-associated changes be elucidated. We studied normal fission in tissue in three dimensions using high-resolution imaging and used intestinal organoids to identify underlying mechanisms. We discovered that both the number and relative position of Paneth cells and Lgr5+ cells are important for fission. Furthermore, the higher stiffness and increased adhesion of Paneth cells are involved in determining the site of fission. Formation of a cluster of Lgr5+ cells between at least two Paneth-cell-rich domains establishes the site for the upward invagination that initiates fission. PMID:27348469

  9. Evaluation of the effects of initial conditions on transients in PUMA

    International Nuclear Information System (INIS)

    A Simplified Boiling Water Reactor (SBWR) is the latest Boiling Water Reactor (BWR) designed by the General Electric (GE). Major differences between the SBWR and the currently operating BWRs include the use of passive gravity-driven systems in the SBWR for emergency cooling of the vessel and containment. In order to investigate the phenomena expected during a Loss of Coolant Accident (LOCA), Nuclear Regulatory Commission (NRC) has sponsored an integral scaled-test facility, called Purdue University Multidimensional Integral Test Assembly (PUMA). The facility models all the major safety-related components of SBWR. Two PUMA initialization calculations were performed to assist the Purdue University in establishing test initialization procedures. Both calculations were based on the initial conditions obtained from SBWR LOCA simulation. In the base case, a complete separation between vapor and liquid was assumed, with all the water in the lower part of the Reactor Pressure Vessel (RPV) and all the vapor above it. In the sensitivity case, the water inventory was distributed in the vessel in the same way as in the SBWR at 1.034 MPa, which is the initial pressure for PUMA facility. Purdue University plans to initialize the PUMA tests as in the base case. The sensitivity calculation is performed to provide assurance that this mode of initialization is adequate. It also provides information on possible differences in the progress of transients. The paper will discuss the differences in the early part of the transient. The conclusion from this study will also apply to many integral facilities which simulate the reactor transients form the middle of the transient

  10. Implementation of a Process for Initial Transcranial Doppler Ultrasonography in Children With Sickle Cell Anemia.

    Science.gov (United States)

    Crosby, Lori E; Joffe, Naomi E; Davis, Blair; Quinn, Charles T; Shook, Lisa; Morgan, Darice; Simmons, Kenya; Kalinyak, Karen A

    2016-07-01

    Stroke, a devastating complication of sickle cell anemia (SCA), can cause irreversible brain injury with physical and cognitive deficits. Transcranial Doppler ultrasonography (TCD) is a non-invasive tool for identifying children with SCA at highest risk of stroke. National guidelines recommend that TCD screening begin at age 2 years, yet there is research to suggest less than half of young children undergo screening. The purpose of this project was to use quality improvement methods to improve the proportion of patients aged 24-27 months who successfully completed their initial TCD from 25% to 75% by December 31, 2013. Quality improvement methods (e.g., process mapping, simplified failure mode effect analysis, and plan-do-study-act cycles) were used to develop and test processes for identifying eligible patients, scheduling TCDs, preparing children and families for the first TCD, and monitoring outcomes (i.e., TCD protocol). Progress was tracked using a report of eligible patients and a chart showing the age in months for the first successful TCD (population metric). As of December 2013, 100% of eligible patients successfully completed their initial TCD screen; this improvement was maintained for the next 20 months. In November 2014, a Welch's one-way ANOVA was conducted. Results showed a statistically significant difference between the average age of first TCD for eligible patients born in 2009 and eligible patients born during the intervention period (2010-2013; F[1,11.712]=16.03, p=0.002). Use of quality improvement methods to implement a TCD protocol was associated with improved TCD screening rates in young children with SCA. PMID:27320459

  11. BC Transit Fuel Cell Bus Project: Evaluation Results Report

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Post, M.

    2014-02-01

    This report evaluates a fuel cell electric bus demonstration led by British Columbia Transit (BC Transit) in Whistler, Canada. BC Transit is collaborating with the California Air Resources Board and the U.S. Department of Energy's National Renewable Energy Laboratory to evaluate the buses in revenue service. This evaluation report covers two years of revenue service data on the buses from April 2011 through March 2013.

  12. Open Zinc Freezing-Point Cell Assembly and Evaluation

    Science.gov (United States)

    Žužek, V.; Batagelj, V.; Drnovšek, J.; Bojkovski, J.

    2014-07-01

    An open metal freezing-point cell design has been developed in the Laboratory of Metrology and Quality. According to our design, a zinc cell was successfully assembled. The paper presents the needed parts for the cell, the cleaning process, and sealing of the cell. The assembled cell was then evaluated by comparison with two commercial closed zinc cells of different manufacturers. The freezing plateaus of the cells were measured, and a direct cell comparison was made. It was shown that the assembled open cell performed better than the used closed cell and was close to the brand new closed cell. The nominal purity of the zinc used for the open cell was 7 N, but the freezing plateau measurement suggests a higher impurity concentration. It was assumed that the zinc was contaminated to some extent during the process of cutting as its original shape was an irregular cylinder. The uncertainty due to impurities for the assembled cell is estimated to be 0.3 mK. Furthermore, the immersion profile and the pressure coefficient were measured. Both results are close to their theoretical values.

  13. Analytical evaluation of fatigue cycles to crack initiation and crack growth during cyclic thermal shocks

    International Nuclear Information System (INIS)

    The thermal shock experiments at the HDR plant are proceeded in the cylindrical part of the reactor pressure vessel. Calculations for prediction of crack initiation and growth are performed and compared to results of non-destructive examinations. Special attention is paid to influencing parameters, like inhomogeneous surface, on crack formation. (orig.)

  14. Quantitative evaluation of fiber fuse initiation with exposure to arc discharge provided by a fusion splicer

    Science.gov (United States)

    Todoroki, Shin-Ichi

    2016-05-01

    The optical communication industry and power-over-fiber applications face a dilemma as a result of the expanding demand of light power delivery and the potential risks of high-power light manipulation including the fiber fuse phenomenon, a continuous destruction of the fiber core pumped by the propagating light and triggered by a heat-induced strong absorption of silica glass. However, we have limited knowledge on its initiation process in the viewpoint of energy flow in the reactive area. Therefore, the conditions required for a fiber fuse initiation in standard single-mode fibers were determined quantitatively, namely the power of a 1480 nm fiber laser and the arc discharge intensity provided by a fusion splicer for one second as an outer heat source. Systematic investigation on the energy flow balance between these energy sources revealed that the initiation process consists of two steps; the generation of a precursor at the heated spot and the transition to a stable fiber fuse. The latter step needs a certain degree of heat accumulation at the core where waveguide deformation is ongoing competitively. This method is useful for comparing the tolerance to fiber fuse initiation among various fibers with a fixed energy amount that was not noticed before.

  15. Group Cognitive-Behavioral Treatment for the Nonpurging Bulimic: An Initial Evaluation.

    Science.gov (United States)

    Telch, Christy F.; And Others

    1990-01-01

    Tested initial effects of cognitive-behavioral therapy for binge eating. Female nonpurging binge eaters (n=44) were randomized to treatment or control groups. At posttreatment, significant difference was found, with 79 percent of treatment subjects reporting abstinence from binge eating and 94 percent decrease in binge eating compared with…

  16. Quantitative evaluation of fiber fuse initiation with exposure to arc discharge provided by a fusion splicer.

    Science.gov (United States)

    Todoroki, Shin-Ichi

    2016-01-01

    The optical communication industry and power-over-fiber applications face a dilemma as a result of the expanding demand of light power delivery and the potential risks of high-power light manipulation including the fiber fuse phenomenon, a continuous destruction of the fiber core pumped by the propagating light and triggered by a heat-induced strong absorption of silica glass. However, we have limited knowledge on its initiation process in the viewpoint of energy flow in the reactive area. Therefore, the conditions required for a fiber fuse initiation in standard single-mode fibers were determined quantitatively, namely the power of a 1480 nm fiber laser and the arc discharge intensity provided by a fusion splicer for one second as an outer heat source. Systematic investigation on the energy flow balance between these energy sources revealed that the initiation process consists of two steps; the generation of a precursor at the heated spot and the transition to a stable fiber fuse. The latter step needs a certain degree of heat accumulation at the core where waveguide deformation is ongoing competitively. This method is useful for comparing the tolerance to fiber fuse initiation among various fibers with a fixed energy amount that was not noticed before. PMID:27140935

  17. Primary pulmonary lymphoma-role of fluoro-deoxy-glucose positron emission tomography-computed tomography in the initial staging and evaluating response to treatment - case reports and review of literature

    Science.gov (United States)

    Agarwal, Krishan Kant; Dhanapathi, Halanaik; Nazar, Aftab Hasan; Kumar, Rakesh

    2016-01-01

    Primary pulmonary lymphoma (PPL) is an uncommon entity of non-Hodgkin lymphoma, which accounts for <1% of all cases of lymphoma. We present two rare cases of PPL of diffuse large B-cell lymphoma, which underwent 18fluorine fluoro-deoxy-glucose positron emission tomography-computed tomography for initial staging and response evaluation after chemotherapy. PMID:27385889

  18. Use of ICRH for startup and initial heating of the TMX-U central cell

    International Nuclear Information System (INIS)

    Ion cyclotron resonance heating (ICRH) was evaluated and it was found to be satisfactory for use in establishing the conditions necessary to form a thermal barrier in TMX-upgrade (TMX-U). We discuss the constraints that must be satisfied in order to maintain a plasma, and outline a complete startup scenario that ends with the plasma at design parameters. The detailed discussions in this report concentrate on those parts of startup where ICRH is necessary. The ability of ICRH to couple power into a plasma at the fundamental ion cyclotron resonance, w/sub ci/, is determined from experiments with a half-turn loop antenna in the Phaedrus tandem mirror central cell. From these experiments, we get the empirical scaling that shows power deposited in the plasma is proportional to the plasma density

  19. Human normal bronchial epithelial cells: a novel in vitro cell model for toxicity evaluation.

    Directory of Open Access Journals (Sweden)

    Wenqiang Feng

    Full Text Available Human normal cell-based systems are needed for drug discovery and toxicity evaluation. hTERT or viral genes transduced human cells are currently widely used for these studies, while these cells exhibited abnormal differentiation potential or response to biological and chemical signals. In this study, we established human normal bronchial epithelial cells (HNBEC using a defined primary epithelial cell culture medium without transduction of exogenous genes. This system may involve decreased IL-1 signaling and enhanced Wnt signaling in cells. Our data demonstrated that HNBEC exhibited a normal diploid karyotype. They formed well-defined spheres in matrigel 3D culture while cancer cells (HeLa formed disorganized aggregates. HNBEC cells possessed a normal cellular response to DNA damage and did not induce tumor formation in vivo by xenograft assays. Importantly, we assessed the potential of these cells in toxicity evaluation of the common occupational toxicants that may affect human respiratory system. Our results demonstrated that HNBEC cells are more sensitive to exposure of 10~20 nm-sized SiO2, Cr(VI and B(aP compared to 16HBE cells (a SV40-immortalized human bronchial epithelial cells. This study provides a novel in vitro human cells-based model for toxicity evaluation, may also be facilitating studies in basic cell biology, cancer biology and drug discovery.

  20. Evaluation of a Mouse Embryonic Stem Cell Adherent Cell Differentiation and Cytotoxicity (ACDC) assay (Keystone Sym)

    Science.gov (United States)

    Our goal is to establish an in vitro model system to evaluate chemical effects using a single stem cell culture technique that would improve throughput and provide quantitative markers of differentiation and cell number. To this end, we have used an adherent cell differentiation ...

  1. Hypoxia attenuates anti-Aspergillus fumigatus immune responses initiated by human dendritic cells.

    Science.gov (United States)

    Fliesser, Mirjam; Wallstein, Marion; Kurzai, Oliver; Einsele, Hermann; Löffler, Jürgen

    2016-08-01

    Aspergillus fumigatus is an opportunistic mould that causes invasive pulmonary aspergillosis (IPA), a life-threatening infection in immunocompromised patients. During the course of IPA, localised areas of tissue hypoxia occur. Bacterial infection models revealed that hypoxic microenvironments modulate the function of host immune cells. However, the influence of hypoxia on anti-fungal immunity has been largely unknown. We evaluated the impact of hypoxia on the human anti-A. fumigatus immune response. Human monocyte-derived dendritic cells (DCs) were stimulated in vitro with germ tubes of A. fumigatus under normoxia or hypoxia (1% O2 ), followed by analysis of DC viability, maturation and cytokine release. While DC viability was unaffected, hypoxia attenuated cytokine release from DCs and maturation of DCs upon stimulation with A. fumigatus. These data suggest that hypoxia at the site of A. fumigatus infection inhibits full activation and function of human DCs. Thereby, this study identified hypoxia as a crucial immune-modulating factor in the human anti-fungal immune response that might influence the course and outcome of IPA in immunocompromised patients. PMID:27005862

  2. Evaluation of multi-level social learning for sustainable landscapes: perspective of a development initiative in Bergslagen, Sweden.

    Science.gov (United States)

    Axelsson, Robert; Angelstam, Per; Myhrman, Lennart; Sädbom, Stefan; Ivarsson, Milis; Elbakidze, Marine; Andersson, Kenneth; Cupa, Petr; Diry, Christian; Doyon, Frederic; Drotz, Marcus K; Hjorth, Arne; Hermansson, Jan Olof; Kullberg, Thomas; Lickers, F Henry; McTaggart, Johanna; Olsson, Anders; Pautov, Yurij; Svensson, Lennart; Törnblom, Johan

    2013-03-01

    To implement policies about sustainable landscapes and rural development necessitates social learning about states and trends of sustainability indicators, norms that define sustainability, and adaptive multi-level governance. We evaluate the extent to which social learning at multiple governance levels for sustainable landscapes occur in 18 local development initiatives in the network of Sustainable Bergslagen in Sweden. We mapped activities over time, and interviewed key actors in the network about social learning. While activities resulted in exchange of experiences and some local solutions, a major challenge was to secure systematic social learning and make new knowledge explicit at multiple levels. None of the development initiatives used a systematic approach to secure social learning, and sustainability assessments were not made systematically. We discuss how social learning can be improved, and how a learning network of development initiatives could be realized. PMID:23475659

  3. Cell Length Independent PBRB Model for Simulations of HE Reaction Initiation, Growth, and Detonation

    Science.gov (United States)

    Dwivedi, Sunil

    2015-06-01

    It has been our focus to use the Physics Based Reaction Burn (PBRB) model to simulate reaction initiation, growth, and detonation of HE composites at the mesoscale. The idealization of hot spots as planar surfaces reduces the 3D model to a 1D hot spot cell (1DHSC) model. The idealization also renders the model dependent on the 1DHSC length and mesh size. New developments are presented making the PBRB model 1DHSC length independent. First, the accurate prediction of the gas-solid interface temperature and thermal gradient are essential, achieved through a finite difference scheme with 500-2000 thermal grid points. Second, keeping the burn mass constant while varying the 1DHSC length is essential, achieved by varying the hot spot specific surface area. 1D and 2D simulation results are presented for shock response of RDX at 1 km/s and 2 km/s impact velocities. The 5, 10, and 50 micro meters 1DHSC lengths yield near identical run-to-detonation, time-to-detonation, and detonation velocity in agreement with experimental data. It is concluded that the new developments make the PBRB model well suited as a generic EOS model for HE composites. - Dr. John Brennan, ARL is acknowledged for his interactions and support. This work is supported in part by ARL Grant W911NF-12-2-0053 and DTRA Grant HDTRA1-12-1-0004.

  4. PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells

    Science.gov (United States)

    Rogers, Samuel; Fey, Dirk; McCloy, Rachael A.; Parker, Benjamin L.; Mitchell, Nicholas J.; Payne, Richard J.; Daly, Roger J.; James, David E.; Caldon, C. Elizabeth; Watkins, D. Neil; Croucher, David R.; Burgess, Andrew

    2016-01-01

    ABSTRACT Entry into mitosis is driven by the phosphorylation of thousands of substrates, under the master control of Cdk1. During entry into mitosis, Cdk1, in collaboration with MASTL kinase, represses the activity of the major mitotic protein phosphatases, PP1 and PP2A, thereby ensuring mitotic substrates remain phosphorylated. For cells to complete and exit mitosis, these phosphorylation events must be removed, and hence, phosphatase activity must be reactivated. This reactivation of phosphatase activity presumably requires the inhibition of MASTL; however, it is not currently understood what deactivates MASTL and how this is achieved. In this study, we identified that PP1 is associated with, and capable of partially dephosphorylating and deactivating, MASTL during mitotic exit. Using mathematical modelling, we were able to confirm that deactivation of MASTL is essential for mitotic exit. Furthermore, small decreases in Cdk1 activity during metaphase are sufficient to initiate the reactivation of PP1, which in turn partially deactivates MASTL to release inhibition of PP2A and, hence, create a feedback loop. This feedback loop drives complete deactivation of MASTL, ensuring a strong switch-like activation of phosphatase activity during mitotic exit. PMID:26872783

  5. Support for the initial attachment, growth and differentiation of MG-63 cells: a comparison between nano-size hydroxyapatite and micro-size hydroxyapatite in composites.

    Science.gov (United States)

    Filová, Elena; Suchý, Tomáš; Sucharda, Zbyněk; Supová, Monika; Zaloudková, Margit; Balík, Karel; Lisá, Věra; Slouf, Miroslav; Bačáková, Lucie

    2014-01-01

    Hydroxyapatite (HA) is considered to be a bioactive material that favorably influences the adhesion, growth, and osteogenic differentiation of osteoblasts. To optimize the cell response on the hydroxyapatite composite, it is desirable to assess the optimum concentration and also the optimum particle size. The aim of our study was to prepare composite materials made of polydimethylsiloxane, polyamide, and nano-sized (N) or micro-sized (M) HA, with an HA content of 0%, 2%, 5%, 10%, 15%, 20%, 25% (v/v) (referred to as N0-N25 or M0-M25), and to evaluate them in vitro in cultures with human osteoblast-like MG-63 cells. For clinical applications, fast osseointegration of the implant into the bone is essential. We observed the greatest initial cell adhesion on composites M10 and N5. Nano-sized HA supported cell growth, especially during the first 3 days of culture. On composites with micro-size HA (2%-15%), MG-63 cells reached the highest densities on day 7. Samples M20 and M25, however, were toxic for MG-63 cells, although these composites supported the production of osteocalcin in these cells. On N2, a higher concentration of osteopontin was found in MG-63 cells. For biomedical applications, the concentration range of 5%-15% (v/v) nano-size or micro-size HA seems to be optimum. PMID:25125978

  6. Baseline Survey for an Impact Evaluation of the Greenbelt Transformation Initiative in South Sudan

    Data.gov (United States)

    US Agency for International Development — This data set is derived from a 2013 household baseline survey in the country's Greenbelt region as part of an impact evaluation of the Food, Agribusiness, and...

  7. Evaluation of nonlocal parameter in the vibrations of single-walled carbon nanotubes with initial strain

    Science.gov (United States)

    Arash, B.; Ansari, R.

    2010-06-01

    Based upon a nonlocal shell model accounting for the small-scale effects, the vibration characteristics of single-walled carbon nanotubes (SWCNTs) with different boundary conditions subjected to initial strain are studied in this paper. The set of governing equations of motion is numerically solved by a method that emerged from incorporating the radial point interpolation approximation within the framework of the generalized differential quadrature method. The effectiveness of the present nonlocal shell model is assessed by the molecular dynamics simulations as a benchmark of good accuracy. Accordingly, nonlocal parameters for clamped and cantilever SWCNTs with thicknesses of 0.066 and 0.34 nm are proposed due to the uncertainty that exists in defining nanotube wall thickness. The simulation results show that the resonant frequencies of SWCNTs are very sensitive to the initial strain, although small.

  8. Evaluation of an Implementation Initiative for Embedding Dialectical Behavior Therapy in Community Settings

    OpenAIRE

    Herschell, Amy D.; Lindhiem, Oliver J.; Kogan, Jane N.; Celedonia, Karen L.; Stein, Bradley D.

    2013-01-01

    We examined the effectiveness of Dialectical Behavior Therapy (DBT) training in community-based agencies. Data were gathered at four time points over a two-year period from front-line mental health therapists (N = 64) from 10 community-based agencies that participated in a DBT implementation initiative. We examined change on therapist attitudes towards consumers with Borderline Personality Disorder (BPD), confidence in the effectiveness of DBT, and use of DBT model components. All measures we...

  9. Evaluation of a Practice-Development Initiative to Improve Breastfeeding Rates

    OpenAIRE

    Barnes, Margaret; Cox, Julie; Doyle, Bronwyn; Reed, Rachel

    2010-01-01

    The benefits of breastfeeding for infant, mother, family, and community are well recognized, and increasing breastfeeding rates is considered an important health-promotion strategy. Improving breastfeeding knowledge and practice among individuals caring for breastfeeding women is considered an important aspect of this strategy. The practice-development initiative described in this article aimed to improve hospital-based breastfeeding rates through the implementation of The Ten Steps to Succes...

  10. Quantitative evaluation of fiber fuse initiation with exposure to arc discharge provided by a fusion splicer

    OpenAIRE

    Todoroki, Shin-ichi

    2016-01-01

    The optical communication industry and power-over-fiber applications face a dilemma as a result of the expanding demand of light power delivery and the potential risks of high-power light manipulation including the fiber fuse phenomenon, a continuous destruction of the fiber core pumped by the propagating light and triggered by a heat-induced strong absorption of silica glass. However, we have limited knowledge on its initiation process in the viewpoint of energy flow in the reactive area. Th...

  11. Initial evaluation of ultrasonic attenuation measurements for estimating fracture toughness of RPV steels

    Energy Technology Data Exchange (ETDEWEB)

    Hiser, A.L. Jr.; Green, R.E. Jr. [Johns Hopkins Univ., Baltimore, MD (United States). Center for Nondestructive Evaluation

    1999-08-01

    Neutron bombardment of reactor pressure vessel (RPV) steels causes reductions in fracture toughness in these steels, termed neutron irradiation embrittlement. Currently, there are no accepted methods for nondestructive determination of the extent of the irradiation embrittlement nor the actual fracture toughness of the reactor pressure vessel. This paper provides initial results of an effort addressing the use of ultrasonic attenuation as a suitable parameter for nondestructive determination of irradiation embrittlement in RPV steels. (orig.)

  12. Participation in Risk Management Decisions: Theoretical, Practical, and Strategic Difficulties in the Evaluation of Public Participation Initiatives

    International Nuclear Information System (INIS)

    A current trend in risk management, and policy setting more generally, is the involvement of members of the public, or other significant stakeholders, in the decision-making process. Such involvement has been argued to have the advantage of increasing the democratic legitimacy of decisions, and allowing the incorporation of lay insight into problems that have a degree of scientific uncertainty (and hence that are based to some extent on value judgments). One significant issue is the quality or validity of such processes, namely, the issue of evaluation. Evaluation is important, not only from a quality control perspective, but because it may indicate potential improvements for the conduct of further exercises, and importantly, may help to assure participants (and the public more widely) that the exercise is more than just a public relations exercise. However, evaluation of public involvement initiatives is relatively rare, and little discussed in the academic literature. It is also beset with a large number of potential problems and uncertainties. In this paper, we will discuss a variety of problems with conducting evaluations of participation initiatives. These problems range from the theoretical (how one defines effectiveness, how one measures this, how one confirms the validity, reliability and utility of one's measures), to the practical (how one conducts evaluations given limitations in time, space, resources, and possible sources of data), to the strategic/political (how one deals with sponsor/organiser resistance to evaluation). These problems will be discussed from a theoretical point of view, and with reference to practical evaluations that we have conducted with a large variety of governmental and non-governmental organisations, predominantly in the UK. The paper will conclude with a number of recommendations regarding best practice in conducting evaluations

  13. Evaluation of Multi-level Social Learning for Sustainable Landscapes: Perspective of a Development Initiative in Bergslagen, Sweden

    OpenAIRE

    Axelsson, Robert; Angelstam, Per; Myhrman, Lennart; Sädbom, Stefan; Ivarsson, Milis; Elbakidze, Marine; Andersson, Kenneth; Cupa, Petr; Diry, Christian; Doyon, Frederik; Drotz, Marcus; Hjorth, Arne; Hermansson, Jan Olof; Kullberg, Thomas; Lickers, F. Henry

    2013-01-01

    To implement policies about sustainable landscapes and rural development necessitates social learning about states and trends of sustainability indicators, norms that define sustainability, and adaptive multi-level governance. We evaluate the extent to which social learning at multiple governance levels for sustainable landscapes occur in 18 local development initiatives in the network of Sustainable Bergslagen in Sweden. We mapped activities over time, and interviewed key actors in the netwo...

  14. Implementing healthy lifestyle promotion in primary care: a quasi-experimental cross-sectional study evaluating a team initiative

    OpenAIRE

    Andersson, Kristin; Krevers, Barbro; Bendtsen, Preben

    2015-01-01

    Background: Non-communicable diseases are a leading cause of death and can largely be prevented by healthy lifestyles. Health care organizations are encouraged to integrate healthy lifestyle promotion in routine care. This study evaluates the impact of a team initiative on healthy lifestyle promotion in primary care. Methods: A quasi-experimental, cross-sectional design compared three intervention centres that had implemented lifestyle teams with three control centres that used a traditional ...

  15. Evaluation of a pharmacist intervention on patients initiating pharmacological treatment for depression: a randomized controlled superiority trial

    OpenAIRE

    Rubio Valera, Maria; March Pujol, Marian; Fernández Sánchez, Ana; Peñarrubia María, María Teresa; Travé i Mercadé, Pere; López del Hoyo, Yolanda; Serrano Blanco, Antoni

    2013-01-01

    Major depression is associated with high burden, disability and costs. Non-adherence limits the effectiveness of antidepressants. Community pharmacists (CP) are in a privileged position to help patients cope with antidepressant treatment. The aim of the study was to evaluate the impact of a CP intervention on primary care patients who had initiated antidepressant treatment. Newly diagnosed primary care patients were randomised to usual care (UC) (92) or pharmacist intervention (87). Patients ...

  16. Height distribution of the Kardar-Parisi-Zhang equation with sharp-wedge initial condition: Numerical evaluations

    Science.gov (United States)

    Prolhac, Sylvain; Spohn, Herbert

    2011-07-01

    The time-dependent probability distribution function of the height for the Kardar-Parisi-Zhang equation with sharp wedge initial conditions has been obtained recently as a convolution between the Gumbel distribution and a difference of two Fredholm determinants. We evaluate numerically this distribution over the whole time span. The crossover from the short time behavior, which is Gaussian, to the long time behavior, which is governed by the Gaussian unitary ensemble (GUE) Tracy-Widom distribution, is clearly visible.

  17. Copine A plays a role in the differentiation of stalk cells and the initiation of culmination in Dictyostelium development

    Directory of Open Access Journals (Sweden)

    Donaghy Alex C

    2010-06-01

    Full Text Available Abstract Background Copines are calcium-dependent phospholipid-binding proteins found in diverse eukaryotic organisms. We are studying the function of copines in Dictyostelium discoideum, a single-celled amoeba that undergoes cell differentiation and morphogenesis to form multicellular fruiting bodies when placed in starvation conditions. Previously, we showed that Dictyostelium cells lacking the copine A (cpnA gene are not able to complete the developmental cycle, arresting at the slug stage. The aim of this study is to further characterize the developmental defect of the cpnA- cells. Results Time-lapse imaging revealed that cpnA- cells exhibited delayed aggregation and made large mounds that formed one large slug as compared to the smaller slugs of the wild-type cells. While the prespore cell patterning appeared to be normal within the cpnA- slugs, the prestalk cell patterning was different from wild-type. When cpnA- cells were mixed with a small percentage of wild-type cells, chimeric fruiting bodies with short stalks formed. When a small percentage of cpnA- cells was mixed with wild-type cells, the cpnA- cells labeled with GFP were found located throughout the chimeric slug and in both the stalk and sporehead of the fruiting bodies. However, there appeared to be a small bias towards cpnA- cells becoming spore cells. When cpnA- cells were developed in buffer containing EGTA, they were also able to differentiate into either stalk or spore cells to form fruiting bodies with short stalks. Conclusions Our results indicate that CpnA is involved in the regulation of aggregation, slug size, and culmination during Dictyostelium development. More specifically, CpnA appears to be involved in the function and differentiation of prestalk cells and plays a role in a calcium-regulated signaling pathway critical to triggering the initiation of culmination.

  18. Utility of PET-FDG in renal cell carcinoma: evaluation in our habitat

    International Nuclear Information System (INIS)

    The great utility of FDG-PET in most oncologic diseases is well known. One of the limitations of the FDG-PET is for the evaluation of renal carcinoma. For better evaluation of the usefulness of FDG-PET in renal cell carcinoma, we reviewed several studies about the subject and compared the results with our own FDG-PET study on patients with renal carcinoma. Results of most studies are clearly influenced by the reason for which the FDG-PET study was requested: initial diagnosis, staging or re-staging. Our results demonstrate that optimizing patient preparation and using flexible study protocols, better results than reported can be achieved

  19. Reflective practice groups for nurses: a consultation liaison psychiatry nursing initiative: part 2--the evaluation.

    Science.gov (United States)

    Dawber, Chris

    2013-06-01

    This paper outlines an evaluation of reflective practice groups (RPG) involving nurses and midwives from three clinical nursing specialties at Redcliffe and Caboolture Hospitals, Queensland, Australia. The groups were facilitated by the consultation liaison psychiatry nurse and author using a process-focused, whole-of-group approach to explore clinical narrative in a supportive group setting. This was a preliminary evaluation utilizing a recently-developed tool, the Clinical Supervision Evaluation Questionnaire, along with externally-facilitated focus groups. Nurses and midwives responded favourably to RPG, reporting a positive impact on clinical practice, self-awareness, and resilience. The majority of participants considered RPG had positive implications for team functioning. The focus groups identified the importance of facilitation style and the need to address aspects of workplace culture to enable group development and enhance the capacity for reflection. Evaluation of the data indicates this style of RPG can improve reflective thinking, promote team cohesion, and provide support for nurses and midwives working in clinical settings. Following on from this study, a second phase of research has commenced, providing more detailed, longitudinal evaluation across a larger, more diverse group of nurses. PMID:23020828

  20. Proteotoxic stress induces a cell-cycle arrest by stimulating Lon to degrade the replication initiator DnaA.

    Science.gov (United States)

    Jonas, Kristina; Liu, Jing; Chien, Peter; Laub, Michael T

    2013-08-01

    The decision to initiate DNA replication is a critical step in the cell cycle of all organisms. Cells often delay replication in the face of stressful conditions, but the underlying mechanisms remain incompletely defined. Here, we demonstrate in Caulobacter crescentus that proteotoxic stress induces a cell-cycle arrest by triggering the degradation of DnaA, the conserved replication initiator. A depletion of available Hsp70 chaperone, DnaK, either through genetic manipulation or heat shock, induces synthesis of the Lon protease, which can directly degrade DnaA. Unexpectedly, we find that unfolded proteins, which accumulate following a loss of DnaK, also allosterically activate Lon to degrade DnaA, thereby ensuring a cell-cycle arrest. Our work reveals a mechanism for regulating DNA replication under adverse growth conditions. Additionally, our data indicate that unfolded proteins can actively and directly alter substrate recognition by cellular proteases. PMID:23911325

  1. Human tumor cell proliferation evaluated using manganese-enhanced MRI.

    Directory of Open Access Journals (Sweden)

    Rod D Braun

    Full Text Available BACKGROUND: Tumor cell proliferation can depend on calcium entry across the cell membrane. As a first step toward the development of a non-invasive test of the extent of tumor cell proliferation in vivo, we tested the hypothesis that tumor cell uptake of a calcium surrogate, Mn(2+ [measured with manganese-enhanced MRI (MEMRI], is linked to proliferation rate in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Proliferation rates were determined in vitro in three different human tumor cell lines: C918 and OCM-1 human uveal melanomas and PC-3 prostate carcinoma. Cells growing at different average proliferation rates were exposed to 1 mM MnCl(2 for one hour and then thoroughly washed. MEMRI R(1 values (longitudinal relaxation rates, which have a positive linear relationship with Mn(2+ concentration, were then determined from cell pellets. Cell cycle distributions were determined using propidium iodide staining and flow cytometry. All three lines showed Mn(2+-induced increases in R(1 compared to cells not exposed to Mn(2+. C918 and PC-3 cells each showed a significant, positive correlation between MEMRI R(1 values and proliferation rate (p≤0.005, while OCM-1 cells showed no significant correlation. Preliminary, general modeling of these positive relationships suggested that pellet R(1 for the PC-3 cells, but not for the C918 cells, could be adequately described by simply accounting for changes in the distribution of the cell cycle-dependent subpopulations in the pellet. CONCLUSIONS/SIGNIFICANCE: These data clearly demonstrate the tumor-cell dependent nature of the relationship between proliferation and calcium influx, and underscore the usefulness of MEMRI as a non-invasive method for investigating this link. MEMRI is applicable to study tumors in vivo, and the present results raise the possibility of evaluating proliferation parameters of some tumor types in vivo using MEMRI.

  2. Human NK cells selective targeting of colon cancer-initiating cells: A role for natural cytotoxicity receptors and MHC class i molecules

    KAUST Repository

    Tallerico, Rossana

    2013-01-23

    Tumor cell populations have been recently proposed to be composed of two compartments: tumor-initiating cells characterized by a slow and asymmetrical growth, and the "differentiated" cancer cells with a fast and symmetrical growth. Cancer stem cells or cancer-initiating cells (CICs) play a crucial role in tumor recurrence. The resistance of CICs to drugs and irradiation often allows them to survive traditional therapy. NK cells are potent cytotoxic lymphocytes that can recognize tumor cells. In this study, we have analyzed the NK cell recognition of tumor target cells derived from the two cancer cell compartments of colon adenocarcinoma lesions. Our data demonstrate that freshly purified allogeneic NK cells can recognize and kill colorectal carcinoma- derived CICs whereas the non-CIC counterpart of the tumors (differentiated tumor cells), either autologous or allogeneic, is less susceptible to NK cells. This difference in the NK cell susceptibility correlates with higher expression on CICs of ligands for NKp30 and NKp44 in the natural cytotoxicity receptor (NCR) group of activating NK receptors. In contrast, CICs express lower levels of MHC class I, known to inhibit NK recognition, on their surface than do the "differentiated" tumor cells. These data have been validated by confocal microscopy where NCR ligands and MHC class I molecule membrane distribution have been analyzed. Moreover, NK cell receptor blockade in cytotoxicity assays demonstrates that NCRs play a major role in the recognition of CIC targets. This study strengthens the idea that biology-based therapy harnessing NK cells could be an attractive opportunity in solid tumors. Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved.

  3. Initial Probabilistic Evaluation of Reactor Pressure Vessel Fracture with Grizzly and Raven

    International Nuclear Information System (INIS)

    The Grizzly code is being developed with the goal of creating a general tool that can be applied to study a variety of degradation mechanisms in nuclear power plant components. The first application of Grizzly has been to study fracture in embrittled reactor pressure vessels (RPVs). Grizzly can be used to model the thermal/mechanical response of an RPV under transient conditions that would be observed in a pressurized thermal shock (PTS) scenario. The global response of the vessel provides boundary conditions for local models of the material in the vicinity of a flaw. Fracture domain integrals are computed to obtain stress intensity factors, which can in turn be used to assess whether a fracture would initiate at a pre-existing flaw. These capabilities have been demonstrated previously. A typical RPV is likely to contain a large population of pre-existing flaws introduced during the manufacturing process. This flaw population is characterized stastistically through probability density functions of the flaw distributions. The use of probabilistic techniques is necessary to assess the likelihood of crack initiation during a transient event. This report documents initial work to perform probabilistic analysis of RPV fracture during a PTS event using a combination of the RAVEN risk analysis code and Grizzly. This work is limited in scope, considering only a single flaw with deterministic geometry, but with uncertainty introduced in the parameters that influence fracture toughness. These results are benchmarked against equivalent models run in the FAVOR code. When fully developed, the RAVEN/Grizzly methodology for modeling probabilistic fracture in RPVs will provide a general capability that can be used to consider a wider variety of vessel and flaw conditions that are difficult to consider with current tools. In addition, this will provide access to advanced probabilistic techniques provided by RAVEN, including adaptive sampling and parallelism, which can dramatically

  4. Initial Probabilistic Evaluation of Reactor Pressure Vessel Fracture with Grizzly and Raven

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, Benjamin [Idaho National Lab. (INL), Idaho Falls, ID (United States); Hoffman, William [Univ. of Idaho, Moscow, ID (United States); Sen, Sonat [Idaho National Lab. (INL), Idaho Falls, ID (United States); Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Dickson, Terry [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bass, Richard [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-10-01

    The Grizzly code is being developed with the goal of creating a general tool that can be applied to study a variety of degradation mechanisms in nuclear power plant components. The first application of Grizzly has been to study fracture in embrittled reactor pressure vessels (RPVs). Grizzly can be used to model the thermal/mechanical response of an RPV under transient conditions that would be observed in a pressurized thermal shock (PTS) scenario. The global response of the vessel provides boundary conditions for local models of the material in the vicinity of a flaw. Fracture domain integrals are computed to obtain stress intensity factors, which can in turn be used to assess whether a fracture would initiate at a pre-existing flaw. These capabilities have been demonstrated previously. A typical RPV is likely to contain a large population of pre-existing flaws introduced during the manufacturing process. This flaw population is characterized stastistically through probability density functions of the flaw distributions. The use of probabilistic techniques is necessary to assess the likelihood of crack initiation during a transient event. This report documents initial work to perform probabilistic analysis of RPV fracture during a PTS event using a combination of the RAVEN risk analysis code and Grizzly. This work is limited in scope, considering only a single flaw with deterministic geometry, but with uncertainty introduced in the parameters that influence fracture toughness. These results are benchmarked against equivalent models run in the FAVOR code. When fully developed, the RAVEN/Grizzly methodology for modeling probabilistic fracture in RPVs will provide a general capability that can be used to consider a wider variety of vessel and flaw conditions that are difficult to consider with current tools. In addition, this will provide access to advanced probabilistic techniques provided by RAVEN, including adaptive sampling and parallelism, which can dramatically

  5. Site Specific Advisory Board initiative, evaluation survey results supplementary appendix: Summary of individual site results

    International Nuclear Information System (INIS)

    This Appendix presents results of the Site-Specific Advisory Board (SSAB) Initiative for each of the 11 sites that participated in the survey. These individual results are a supplement to the June 1996 Summary Report which presented overall survey results. Results are presented in 11 sections, arranged alphabetically by site. Each section includes a series of figures and tables that parallel those presented in the Summary Report. To facilitate comparison, figures are presented both for the individual site and for the overall long survey. The sequence of sections is: Fernald, Hanford, Idaho, Los Alamos, Monticello, Nevada, Pantex, Rocky Flats, St. Louis, Sandia, and Savannah River

  6. Site Specific Advisory Board initiative, evaluation survey results supplementary appendix: Summary of individual site results

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-08-01

    This Appendix presents results of the Site-Specific Advisory Board (SSAB) Initiative for each of the 11 sites that participated in the survey. These individual results are a supplement to the June 1996 Summary Report which presented overall survey results. Results are presented in 11 sections, arranged alphabetically by site. Each section includes a series of figures and tables that parallel those presented in the Summary Report. To facilitate comparison, figures are presented both for the individual site and for the overall long survey. The sequence of sections is: Fernald, Hanford, Idaho, Los Alamos, Monticello, Nevada, Pantex, Rocky Flats, St. Louis, Sandia, and Savannah River.

  7. Tumor Initiating Cells and FZD8 play a major role in drug resistance in Triple-Negative Breast Cancer

    OpenAIRE

    Yin, Shuping; Xu, Liping; Bonfil, R. Daniel; Banerjee, Sanjeev; Sarkar, Fazlul H; Sethi, Seema; Reddy, Kaladhar B.

    2013-01-01

    Triple-negative breast cancer (TNBC) studies have shown that neoadjuvant chemotherapy before surgery was effective in the minority of women, whereas the majority who had residual tumor had a relatively poor outcome. To identify the mechanism by which residual cancer cells survive chemotherapy, we initially performed gene expression profiling using the CRL2335 TNBC cell line derived from a squamous breast carcinoma before and after treatment with cisplatin plus TRAIL. We found a significant in...

  8. Lung cancer tumorigenicity and drug resistance are maintained through ALDHhiCD44hi tumor initiating cells

    OpenAIRE

    Liu, Jing; Xiao, Zhijie; Wong, Sunny Kit-Man; Tin, Vicky Pui-Chi; Ho, Ka-Yan; Wang, Junwen; Sham, Mai-Har; Wong, Maria Pik

    2013-01-01

    Limited improvement in long term survival of lung cancer patients has been achieved by conventional chemotherapy or targeted therapy. To explore the potentials of tumor initiating cells (TIC)-directed therapy, it is essential to identify the cell targets and understand their maintenance mechanisms. We have analyzed the performance of ALDH/CD44 co-expression as TIC markers and treatment targets of lung cancer using well-validated in vitro and in vivo analyses in multiple established and patien...

  9. Search for Chemically Defined Culture Medium to Assist Initial Regeneration of Diseased Renal Parenchyma After Stem/Progenitor Cell Implantation

    OpenAIRE

    Minuth WW; Denk L; Gruber M

    2013-01-01

    Before an intended implantation stem/progenitor cells are usually kept in the beneficial atmosphere of a selected culture medium. However, after implantation the situation is drastically changing for them. Yet stem/progenitor cells must stand the harmful fluid environment within a diseased organ. In this coherence it is unknown, to which degree alterations in molecular composition of interstitial fluid can influence the initial regeneration of parenchyma. To obtain first ins...

  10. Cytotoxicity study of rock wool by cell magnetometric evaluation.

    Science.gov (United States)

    Kudo, Yuichiro; Kotani, Makoto; Aizawa, Yoshiharu

    2009-11-01

    The cytotoxicity of rock wool (RW), an asbestos substitute, was evaluated by cell magnetometry. Alveolar macrophages were isolated from male Fisher rats. Following addition of triiron tetraoxide (Fe(3)O(4)) to macrophages, RW was added. Then, the remnant magnetic field strength was measured for 20min after magnetization by an external field. Relaxation, an indicator of decay of cytotoxicity, was observed by cell magnetometry immediately postmagnetization in the group to which RW was added. In general, materials phagocytosed by macrophages are ingested into phagosomes and digested while migrating. This migration of phagosomes occurs by polymerization and depolymerization of the cytoskeleton. As a result of evaluation, relaxation was not delayed by addition of RW, since RW caused no effect on the cytoskeleton. It was suggested that RW has no cytotoxicity as evaluated by cell magnetometry. PMID:19559064

  11. Manufacture and evaluation of Li/BCX DD cells

    Science.gov (United States)

    Meyer, S.; Takeuchi, E.

    1990-01-01

    This project is divided into four main tasks: cell manufacture, acceptance, and lot certification of cells, performance testing of cells, and abuse testing of cells. Lithium/bromine chloride in thionyl chloride (Li/BCX) 149 DD cells (PN 3B2085-XA) were built according to the provisions of Electrochem Industries Quality Plan 17096. Acceptance and lot certification testing was performed according to NASA JSC Document EP5-83-025, Revision B. Acceptance testing included open circuit and load voltage check, visual examination, size and weight measurements, and high temperature exposure. Lot certification tests were performed for capacity performance and for performance under conditions of thermal and electrical abuse. These tests included 149 C exposure, capacity discharge, fuse check, high temperature exposure, high rate discharge, short circuit, vibration, and overdischarge testing. A quantity of 200 cells was delivered to Johnson Space Center for life test evaluation. A parametric evaluation of the capacity discharge of Li/BCX DD cells was performed over a variety of temperatures and discharge rates. This testing served to map the performance capability of the cell. Tests were also performed over a variety of electrical and thermal abuse conditions. Abuse tests included short circuit, charging, overdischarge, high temperature exposure, shock, and vibration.

  12. Engaging Families in Boys & Girls Clubs: An Evaluation of the Family PLUS Pilot Initiative

    Science.gov (United States)

    Kreider, Holly; Raghupathy, Shobana

    2010-01-01

    Research has shown that engaging families through youth development and after-school programs may benefit children. This paper extends knowledge in this arena, describing a set of strategies for implementing family-strengthening activities in youth development settings. The paper reports findings from a pilot evaluation of the Boys & Girls Clubs…

  13. Initial Evaluation of a Mobile Scaffolding Application That Seeks to Support Novice Learners of Programming

    Science.gov (United States)

    Mbogo, Chao; Blake, Edwin; Suleman, Hussein

    2014-01-01

    The aim of this paper is to explore the use of an application that scaffolds the constructions of programs on a mobile device. The application was developed to support novice learners of programming outside the classroom. This paper reports on results of a first experiment conducted to evaluate the mobile application. The main research questions…

  14. Second Line of Defense, Megaports Initiative, Operational Testing and Evaluation Plan, Port of Lazaro Cardenas, Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, Jamie D.

    2012-05-30

    The purpose of the Operational Testing and Evaluation (OT&E) phases of the project is to prepare for turnover of the Megaports System supplied by U.S. Department of Energy/National Nuclear Security Administration (DOE/NNSA)—located at the Export Lanes of the Port of Lazaro Cardenas, Mexico—to the Government of Mexico (GOM).

  15. Training and Development. An Evaluation of Docklands SKILLNET Quick Start Initiatives. FEU/REPLAN.

    Science.gov (United States)

    Saunders, Lesley

    This report provides results of an evaluation of SKILLNET, an education and training innovation to commission training in the newly redeveloped area of London's dockland. Chapter 1, an introduction, defines SKILLNET's primary function--to address the current mismatch between kinds of jobs available in the area and the levels and kinds of skills…

  16. MRI for the initial evaluation of acute wrist, knee, and ankle trauma

    NARCIS (Netherlands)

    J.J. Nikken (Jeroen)

    2003-01-01

    textabstractIn this thesis we study the application of MRI in acute trauma of wrist, knee, and ankle, evaluating its potentials, its effects, and its costs. Our aim was to use MRI in all patients with acute trauma of wrist, knee, and ankle, without increasing the overall costs to society, potentiall

  17. Initiation of the occupational health evaluation of the organophosphate S-(2-Diisopropylaminoethyl) 0-ethyl methylphosphonothioate

    International Nuclear Information System (INIS)

    In order to insure that personnel are not subjected to as yet unrecognized harards resulting from chronic low level exposures to S-(2-Diisopropylaminothyl) 0-ethyl methylphosphothiolate (VX), a broad based evaluation has been undertaken to discover any problems that might result in workers handling this material. The project is a collaborative effort involving several investigators at LEHR and the campus of UC Davis

  18. Nondestructive cell evaluation techniques in SOFC stack manufacturing

    Science.gov (United States)

    Wunderlich, C.

    2016-04-01

    Independent from the specifics of the application, a cost efficient manufacturing of solid oxide fuel cells (SOFC), its electrolyte membranes and other stack components, leading to reliable long-life stacks is the key for the commercial viability of this fuel cell technology. Tensile and shear stresses are most critical for ceramic components and especially for thin electrolyte membranes as used in SOFC cells. Although stack developers try to reduce tensile stresses acting on the electrolyte by either matching CTE of interconnects and electrolytes or by putting SOFC cells under some pressure - at least during transient operation of SOFC stacks ceramic cells will experience some tensile stresses. Electrolytes are required to have a high Weibull characteristic fracture strength. Practical experiences in stack manufacturing have shown that statistical fracture strength data generated by tests of electrolyte samples give limited information on electrolyte or cell quality. In addition, the cutting process of SOFC electrolytes has a major influence on crack initiation. Typically, any single crack in one the 30 to 80 cells in series connection will lead to a premature stack failure drastically reducing stack service life. Thus, for statistical reasons only 100% defect free SOFC cells must be assembled in stacks. This underlines the need for an automated inspection. So far, only manual processes of visual or mechanical electrolyte inspection are established. Fraunhofer IKTS has qualified the method of optical coherence tomography for an automated high throughput inspection. Alternatives like laser speckle photometry and acoustical methods are still under investigation.

  19. CD44 variant 9 is a potential biomarker of tumor initiating cells predicting survival outcome in hepatitis C virus-positive patients with resected hepatocellular carcinoma.

    Science.gov (United States)

    Kakehashi, Anna; Ishii, Naomi; Sugihara, Eiji; Gi, Min; Saya, Hideyuki; Wanibuchi, Hideki

    2016-05-01

    This study investigated whether the expression of CD44 variant 9 (CD44v9) might be a functional marker of tumor-initiating stem-like cells in primary hepatocellular carcinomas (HCCs) of hepatitis C virus (HCV)(+) patients and provide an indicator of patient survival, as well as associated mechanisms. A total of 90 HCV(+) HCC patients who underwent surgery from 2006 to 2011 were enrolled and monitored for 2-8 years. Expression of CD44v9 was validated immunohistochemically in all HCCs, followed by comparative proteome, survival, and clinicopathological analyses. CD44 variant 8--10 was further evaluated in diethylnitrosamine-induced HCCs of C57Bl/6J mice. Focally localized CD44v(+) cells with a membranous staining pattern were detected in human HCV(+) and mouse HCCs. CD44v9(+) cells of HCCs were predominantly negative for Ki67 and P-p38, indicating decrease of cell proliferation in the CD44v9(+) tumor cell population, likely to be related to suppression of intracellular oxidative stress due to activation of Nrf2-mediated signaling, DNA repair, and inhibition of xenobiotic metabolism. CD44v9 IHC evaluation in 90 HCV(+) HCC cases revealed that positive expression was significantly associated with poor overall and recurrence-free survival, a younger age, poor histological differentiation of HCCs, and high alkaline phosphatase levels compared with patients with negative expression. CD44v9 is concluded to be a potential biomarker of tumor-initiating stem-like cells and a prognostic marker in HCV(+) HCC patients associated with Nrf2-mediated resistance to oxidative stress. PMID:26882440

  20. Performance and degradation evaluation of five different commercial lithium-ion cells

    Energy Technology Data Exchange (ETDEWEB)

    Striebel, Kathryn A.; Shim, Joongpyo

    2004-04-20

    The initial performance of five different types of Li-ion rechargeable batteries, from Quallion Corp, UltraLife Battery and Toshiba, was measured and compared. Cell characterization included variable-rate constant-current cycling, various USDOE pulse-test protocols and full-spectrum electrochemical impedance spectroscopy. Changes in impedance and capacity were monitored during electrochemical cycling under various conditions, including constant-current cycling over 100 percent DOD at a range of temperature and pulse profile cycling over a very narrow range of DOD at room temperature. All cells were found to maintain more than 80 percent of their rated capacity for more than 400 constant current 100 percent DOD cycles. The power fade (or impedance rise) of the cells varied considerably. New methods for interpreting the pulse resistance data were evaluated for their usefulness in interpreting performance mechanism as a function of test protocol and cell design.

  1. Antigen sampling by intestinal M cells is the principal pathway initiating mucosal IgA production to commensal enteric bacteria

    Science.gov (United States)

    Rios, D; Wood, M B; Li, J; Chassaing, B; Gewirtz, A T; Williams, I R

    2016-01-01

    Secretory IgA (SIgA) directed against gut resident bacteria enables the mammalian mucosal immune system to establish homeostasis with the commensal gut microbiota after weaning. Germinal centers (GCs) in Peyer's patches (PPs) are the principal inductive sites where naive B cells specific for bacterial antigens encounter their cognate antigens and receive T-cell help driving their differentiation into IgA-producing plasma cells. We investigated the role of antigen sampling by intestinal M cells in initiating the SIgA response to gut bacteria by developing mice in which receptor activator of nuclear factor-κB ligand (RANKL)-dependent M-cell differentiation was abrogated by conditional deletion of Tnfrsf11a in the intestinal epithelium. Mice without intestinal M cells had profound delays in PP GC maturation and emergence of lamina propria IgA plasma cells, resulting in diminished levels of fecal SIgA that persisted into adulthood. We conclude that M-cell-mediated sampling of commensal bacteria is a required initial step for the efficient induction of intestinal SIgA. PMID:26601902

  2. Implementation and evaluation of a multisite drug usage evaluation program across Australian hospitals - a quality improvement initiative

    Directory of Open Access Journals (Sweden)

    Robertson Marion B

    2011-08-01

    Full Text Available Abstract Background With the use of medicines being a broad and extensive part of health management, mechanisms to ensure quality use of medicines are essential. Drug usage evaluation (DUE is an evidence-based quality improvement methodology, designed to improve the quality, safety and cost-effectiveness of drug use. The purpose of this paper is to describe a national DUE methodology used to improve health care delivery across the continuum through multi-faceted intervention involving audit and feedback, academic detailing and system change, and a qualitative assessment of the methodology, as illustrated by the Acute Postoperative Pain Management (APOP project. Methods An established methodology, consisting of a baseline audit of inpatient medical records, structured patient interviews and general practitioner surveys, followed by an educational intervention and follow-up audit, is used. Australian hospitals, including private, public, metropolitan and regional, are invited to participate on a voluntary basis. De-identified data collected by hospitals are collated and evaluated nationally to provide descriptive comparative analyses. Hospitals benchmark their practices against state and national results to facilitate change. The educational intervention consists of academic detailing, group education, audit and feedback, point-of-prescribing prompts and system changes. A repeat data collection is undertaken to assess changes in practice. An online qualitative survey was undertaken to evaluate the APOP program. Qualitative assessment of hospitals' perceptions of the effectiveness of the overall DUE methodology and changes in procedure/prescribing/policy/clinical practice which resulted from participation were elicited. Results 62 hospitals participated in the APOP project. Among 23 respondents to the evaluation survey, 18 (78% reported improvements in the documentation of pain scores at their hospital. 15 (65% strongly agreed or agreed that

  3. Evaluation of options for disposition of dispersible material in B-Cell

    International Nuclear Information System (INIS)

    The radioactive contaminants in the dispersible material in B-cell of the 324 Building Radiochemical Energy (RE) hot-cell complex at the Hanford Site in southeastern Washington exceed the allowable level. In 1986, there was a spill of 1.3 million curies of concentrated cesium and strontium in B-cell. Cleanup is required, and candidate technologies for cleaning up or otherwise addressing problems associated with the dispersible material are being evaluated by Pacific Northwest Laboratory (PNL). The RE hot-cell complex in 324 Building was constructed in the late 1950s. From the early 1960s until today the complex has been the site of numerous research, development, and demonstration programs using radioactive and hazardous materials. In mid-FY 1988, a program to clean B-cell was initiated. At present, dispersible material has been collected from 45% of the cell floor area, and 64% of the equipment and support racks have been removed from the cell. The evaluation of decontamination procedures are described

  4. Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential

    Science.gov (United States)

    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

    Objective. The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Approach. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Main results. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. Significance. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

  5. Evaluation of Stem Cell Markers, CD44/CD24 in Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Masoud Hashemi Arabi

    2014-05-01

    Four breast cancer cell lines, MCF-7 ، T47D ، MDA-MB231 and MDA-MB468 were purchased from National cell Bank of Iran based in Iran Pasture Institute and were cultured in high glucose DMEM supplemented with 10% FCS. Cells were stained with antiCD44-PE and antiCD24-FITC antibodies and Status of CD44 and CD24 as markers of breast cancer stem cells were evaluated using flow cytometer and fluorescent microscopy.Evaluation of CD44 and CD24 as markers of breast cancer stem cells showed that MDA-MB231 with 97±1.2% CD44+/CD24-/low cells is significantly different from the others that they were mainly CD44 and CD24 positive cells(p

  6. Production of interleukin‑4 in CD133+ cervical cancer stem cells promotes resistance to apoptosis and initiates tumor growth.

    Science.gov (United States)

    Liu, Chun-Tao; Xin, Ying; Tong, Chun-Yan; Li, Bing; Bao, Hong-Li; Zhang, Cai-Yun; Wang, Xue-Hui

    2016-06-01

    The cancer stem cell (CSC) theory suggests that cancer growth and invasion is dictated by the small population of CSCs within the heterogenous tumor. The aim of the present study was to elucidate the cause for chemotherapy failure and the resistance of CSCs to apoptosis. A total of ~2.3% cluster of differentiation (CD)133+ cancer stem‑like side population (SP) cells were identified in cases of uterine cervical cancer. These CD133+ SP cells were found to potently initiate tumor growth and invasion, as they exhibit transcriptional upregulation of stemness genes, including octamer‑binding transcription factor‑4, B‑cell‑specific Moloney murine leukemia virus insertion site‑1, epithelial cell adhesion molecule, (sex determining region Y)‑box 2, Nestin and anti‑apoptotic B cell lymphoma‑2. In addition, the CD133+ SP cells showed resistance to multi‑drug treatment and apoptosis. The present study further showed that the secretion of interleukin‑4 (IL‑4) in CD133+ cervical cancer SP cells promoted cell proliferation and prevented the SP cells from apoptosis. Following the neutralization of IL‑4 with anti‑IL‑4 antibody, the CD133+ SP cells were more sensitive to drug treatment and apoptosis. Therefore, the data obtained in the present study suggested that the autocrine secretion of IL‑4 promotes increased survival and resistance to cell death in CSCs. PMID:27121303

  7. Evaluating hemorrhage in renal cell carcinoma using susceptibility weighted imaging.

    Directory of Open Access Journals (Sweden)

    Wei Xing

    Full Text Available BACKGROUND: Intratumoral hemorrhage is a frequent occurrence in renal cell carcinoma and is an indicator of tumor subtype. We hypothesize that susceptibility weighted imaging (SWI is sensitive to hemorrhage in renal cell carcinoma and can give a more diagnostic image when compared to conventional imaging techniques. MATERIALS AND METHODS: A retrospective review of 32 patients with clear cell renal cell carcinoma was evaluated. All patients underwent magnetic resonance imaging (MRI and 22 out of 32 patients also underwent a computed tomography (CT scan. Hemorrhage was classified into 3 different categories according to shape and distribution. Histopathology was obtained from all masses by radical nephrectomy. The ability to detect the presence of hemorrhage using CT, non-contrast conventional MRI and SWI was evaluated, and the patterns of hemorrhage were compared. RESULTS: Using pathologic results as the gold standard, the sensitivities of non-contrast conventional MRI, SWI and CT in detecting hemorrhage in clear cell renal cell carcinoma were 65.6%, 100% and 22.7%, respectively. Accuracy of non-contrast conventional MRI and SWI in evaluating hemorrhagic patterns were 31.3% and 100%, respectively. CONCLUSION: These results demonstrate that SWI can better reveal hemorrhage and characterize the pattern more accurately than either non-contrast conventional MRI or CT. This suggests that SWI is the technique of choice for detecting hemorrhagic lesions in patients with renal cancer.

  8. A Structural Evaluation of a Large-Scale Quasi-Experimental Microfinance Initiative.

    Science.gov (United States)

    Kaboski, Joseph P; Townsend, Robert M

    2011-09-01

    This paper uses a structural model to understand, predict, and evaluate the impact of an exogenous microcredit intervention program, the Thai Million Baht Village Fund program. We model household decisions in the face of borrowing constraints, income uncertainty, and high-yield indivisible investment opportunities. After estimation of parameters using pre-program data, we evaluate the model's ability to predict and interpret the impact of the village fund intervention. Simulations from the model mirror the data in yielding a greater increase in consumption than credit, which is interpreted as evidence of credit constraints. A cost-benefit analysis using the model indicates that some households value the program much more than its per household cost, but overall the program costs 20 percent more than the sum of these benefits. PMID:22162594

  9. Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

    Czech Academy of Sciences Publication Activity Database

    Yan, B.; Stantic, M.; Zobalová, Renata; Bezawork-Geleta, A.; Stapelberg, M.; Stursa, J.; Prokopová, Kateřina; Dong, L.; Neužil, Jiří

    2015-01-01

    Roč. 15, č. 401 (2015). ISSN 1471-2407 R&D Projects: GA MZd NT14078; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * Mitochondrially targeted vitamin E succinate * Complex II Subject RIV: FD - Oncology ; Hematology Impact factor: 3.362, year: 2014

  10. Initial in vitro evaluations of antibacterial activities of glucosinolate enzymatic hydrolysis products against plant pathogenic bacteria

    OpenAIRE

    Aires, A.; Mota, V.R.; Saavedra, M.J.; Monteiro, A.A.; Simões, M; Rosa, E.A.S.; Bennett, R.N.

    2009-01-01

    Aims: The aim of the study was to evaluate the in vitro antibacterial effects of glucosinolate hydrolysis products (GHP) against plant pathogenic micro-organisms namely Agrobacterium tumefaciens, Erwinia chrysanthemi, Pseudomonas cichorii, Pseudomonas tomato, Xanthomonas campestris and Xanthomonas juglandis. Methods and Results: Using a disc diffusion assay, seven different doses of 10 GHP were tested against each bacteria. The results showed that the isothiocyanates were...

  11. Evaluation of the APEC Environmental Goods Initiative: A Dominant Supplier Approach

    OpenAIRE

    Manzano, George; Prado, Shanti Aubren

    2015-01-01

    The paper evaluates the feasibility of sectoral liberalization of environmental goods for the Asia-Pacific Economic Cooperation (APEC). Using the model originally developed by Wonnacott, it argues for the liberalization of goods predominantly supplied by APEC members, thereby minimizing the free rider problem that usually afflicts most favored nation liberalization. The paper then ranks the different items in the APEC list of environmental goods according to economic advisability, given the p...

  12. Social Pedagogy in the UK today: findings from evaluations of training and development initiatives

    OpenAIRE

    Claire Cameron

    2015-01-01

    Since 2007, workplace based social pedagogic intervention has been taking place in the UK. Until that point, social pedagogy was largely unknown within children’s services practice or training. This paper synthesises findings from 10 evaluation studies that examined social pedagogic intervention in the form of training and development activity in children’s residential care, foster care and related services. The findings are presente...

  13. EnergyFit Nevada (formerly known as the Nevada Retrofit Initiative) final report and technical evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Carvill, Anna; Bushman, Kate; Ellsworth, Amy

    2014-06-17

    The EnergyFit Nevada (EFN) Better Buildings Neighborhood Program (BBNP, and referred to in this document as the EFN program) currently encourages Nevada residents to make whole-house energy-efficient improvements by providing rebates, financing, and access to a network of qualified home improvement contractors. The BBNP funding, consisting of 34 Energy Efficiency Conservation Block Grants (EECBG) and seven State Energy Program (SEP) grants, was awarded for a three-year period to the State of Nevada in 2010 and used for initial program design and implementation. By the end of first quarter in 2014, the program had achieved upgrades in 553 homes, with an average energy reduction of 32% per home. Other achievements included: Completed 893 residential energy audits and installed upgrades in 0.05% of all Nevada single-family homes1 Achieved an overall conversation rate of 38.1%2 7,089,089 kWh of modeled energy savings3 Total annual homeowner energy savings of approximately $525,7523 Efficiency upgrades completed on 1,100,484 square feet of homes3 $139,992 granted in loans to homeowners for energy-efficiency upgrades 29,285 hours of labor and $3,864,272 worth of work conducted by Nevada auditors and contractors4 40 contractors trained in Nevada 37 contractors with Building Performance Institute (BPI) certification in Nevada 19 contractors actively participating in the EFN program in Nevada 1 Calculated using 2012 U.S. Census data reporting 1,182,870 homes in Nevada. 2 Conversion rate through March 31, 2014, for all Nevada Retrofit Initiative (NRI)-funded projects, calculated using the EFN tracking database. 3 OptiMiser energy modeling, based on current utility rates. 4 This is the sum of $3,596,561 in retrofit invoice value and $247,711 in audit invoice value.

  14. Initial Evaluations of LoC Prediction Algorithms Using the NASA Vertical Motion Simulator

    Science.gov (United States)

    Krishnakumar, Kalmanje; Stepanyan, Vahram; Barlow, Jonathan; Hardy, Gordon; Dorais, Greg; Poolla, Chaitanya; Reardon, Scott; Soloway, Donald

    2014-01-01

    Flying near the edge of the safe operating envelope is an inherently unsafe proposition. Edge of the envelope here implies that small changes or disturbances in system state or system dynamics can take the system out of the safe envelope in a short time and could result in loss-of-control events. This study evaluated approaches to predicting loss-of-control safety margins as the aircraft gets closer to the edge of the safe operating envelope. The goal of the approach is to provide the pilot aural, visual, and tactile cues focused on maintaining the pilot's control action within predicted loss-of-control boundaries. Our predictive architecture combines quantitative loss-of-control boundaries, an adaptive prediction method to estimate in real-time Markov model parameters and associated stability margins, and a real-time data-based predictive control margins estimation algorithm. The combined architecture is applied to a nonlinear transport class aircraft. Evaluations of various feedback cues using both test and commercial pilots in the NASA Ames Vertical Motion-base Simulator (VMS) were conducted in the summer of 2013. The paper presents results of this evaluation focused on effectiveness of these approaches and the cues in preventing the pilots from entering a loss-of-control event.

  15. Evaluation of optimization strategies and the effect of initial conditions on IMAT optimization using a leaf position optimization algorithm

    International Nuclear Information System (INIS)

    Intensity-modulated arc therapy (IMAT) is a rotational variant of intensity-modulated radiation therapy (IMRT) that can be implemented with or without angular dose rate variation. The purpose of this study is to assess optimization strategies and initial conditions using a leaf position optimization (LPO) algorithm altered for variable dose rate IMAT. A concave planning target volume (PTV) with a central cylindrical organ at risk (OAR) was used in this study. The initial IMAT arcs were approximated by multiple static beams at 5 deg. angular increments where multi-leaf collimator (MLC) leaf positions were determined from the beam's eye view to irradiate the PTV but avoid the OAR. For the optimization strategy, two arcs with arc ranges of 280 deg. and 150 deg. were employed and plans were created using LPO alone, variable dose rate optimization (VDRO) alone, simultaneous LPO and VDRO and sequential combinations of these strategies. To assess the MLC initialization effect, three single 360 deg. arc plans with different initial MLC configurations were generated using the simultaneous LPO and VDRO. The effect of changing optimization degrees of freedom was investigated by employing 3 deg., 5 deg. and 10 deg. angular sampling intervals for the two 280 deg., two 150 deg. and single arc plans using LPO and VDRO. The objective function value, a conformity index, a dose homogeneity index, mean dose to OAR and normal tissues were computed and used to evaluate the treatment plans. This study shows that the best optimization strategy for a concave target is to use simultaneous MLC LPO and VDRO. We found that the optimization result is sensitive to the choice of initial MLC aperture shapes suggesting that an LPO-based IMAT plan may not be able to overcome local minima for this geometry. In conclusion, simultaneous MLC leaf position and VDRO are needed with the most appropriate initial conditions (MLC positions, arc ranges and number of arcs) for IMAT.

  16. Evaluation of hela cell lineage response to β radiation from Holmium-166 embedded in ceramic seeds

    Directory of Open Access Journals (Sweden)

    Eduardo Sarmento Valente

    2011-10-01

    Full Text Available This work studied the effects of β radiation of Ho-166 embedded in ceramic seeds on HeLa cells. Methodology consisted in the production of ceramic seeds with holmium-165 by sol-gel route. Chemical and physical characterizations of the seeds were performed. Subsequently, nuclear characterization was performed by gamma spectrometry. Experimental and theoretical activities were defined and initial dose rate were evaluated by MIRD (Medical Internal Radiation Dose Committee methodology. The seeds were placed in confluent culture flasks and remained for six radionuclide half-lives. Biological results were represented by a clean 6 mm diameter area around the seed where the tumour cells were killed. The initial dose rate was 15.5 Gy. h-1. The maximum absorbed dose was 591.3 Gy. The features of the Ho-166 seeds suggested that such ceramic seeds were suitable for high dose rate brachytherapy.

  17. Identification and characterization of cancer initiating cells from BRCA1 related mammary tumors using markers for normal mammary stem cells

    Directory of Open Access Journals (Sweden)

    Athanassios Vassilopoulos, Rui-Hong Wang, Constantinos Petrovas, David Ambrozak, Richard Koup, Chu-Xia Deng

    2008-01-01

    Full Text Available It is hypothesized that cancer stem cells arise either from normal stem cells or from progenitor cells that have gained the ability to self-renew. Here we determine whether mammary cancer stem cells can be isolated by using antibodies that have been used for the isolation of normal mammary stem cells. We show that BRCA1 mutant cancer cell lines contained a subpopulation of CD24+CD29+ or CD24+CD49f+ cells that exhibited increased proliferation and colony forming ability in vitro, and enhanced tumor-forming ability in vivo. The purified CD24+CD29+ cells could differentiate and reconstitute the heterogeneity found in parental cells when plated as a monolayer. Under low-attachment conditions, we detected “tumorspheres” only in the presence of double positive cells, which maintained their ability to self-renew. Furthermore, CD24+CD29+ cells could form tubular structures reminiscent of the mammary ductal tree when grown in three-dimensional cultures, implying that these cancer cells maintain some of the characteristics of the normal stem cells. Nevertheless, they could still drive tumor formation since as low as 500 double positive cells immediately after sorting from BRCA1 mutant primary tumors were able to form tumors with the same heterogeneity found in the original tumors. These data provide evidence that breast cancer stem cells originate from normal stem cells and advance our understanding of BRCA1-associated tumorigenesis with possible implications for future cancer treatment.

  18. Isolation of intestinal epithelial cells and evaluation of transport functions

    Energy Technology Data Exchange (ETDEWEB)

    Kimmich, G.A.

    1990-01-01

    Epithelial cells can be isolated from the small intestine of chickens by a procedure involving hyaluronidase treatment of the intact tissue. The isolated cells retain a high degree of functional activity as assessed by the formation of 70-fold gradients of alpha-MG. Stability of the sugar gradients reflects maintenance of stable electrochemical Na+ gradients across the plasma membrane. The cells can be used to evaluate the properties of Na(+)-dependent sugar transport, Na(+)-independent sugar transport, ion transport, metabolism, membrane potentials, and the integration of these events, all of which are important to achieving a stable sugar gradient.

  19. Isolation of intestinal epithelial cells and evaluation of transport functions

    International Nuclear Information System (INIS)

    Epithelial cells can be isolated from the small intestine of chickens by a procedure involving hyaluronidase treatment of the intact tissue. The isolated cells retain a high degree of functional activity as assessed by the formation of 70-fold gradients of alpha-MG. Stability of the sugar gradients reflects maintenance of stable electrochemical Na+ gradients across the plasma membrane. The cells can be used to evaluate the properties of Na(+)-dependent sugar transport, Na(+)-independent sugar transport, ion transport, metabolism, membrane potentials, and the integration of these events, all of which are important to achieving a stable sugar gradient

  20. Identification and characterization of cancer initiating cells from BRCA1 related mammary tumors using markers for normal mammary stem cells

    OpenAIRE

    Vassilopoulos, Athanassios; Wang, Rui-Hong; Petrovas, Constantinos; Ambrozak, David; Koup, Richard; Deng, Chu-Xia

    2008-01-01

    It is hypothesized that cancer stem cells arise either from normal stem cells or from progenitor cells that have gained the ability to self-renew. Here we determine whether mammary cancer stem cells can be isolated by using antibodies that have been used for the isolation of normal mammary stem cells. We show that BRCA1 mutant cancer cell lines contained a subpopulation of CD24+CD29+ or CD24+CD49f+ cells that exhibited increased proliferation and colony forming ability in vitro, and enhanced ...

  1. Evaluation of cell cytotoxic effect on herbal extracts mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong Soo; Gwon, Hui Jeong; Choi, Bo Ram; Lim, Youn Mook; Nho, Young Chang [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2009-12-15

    Herbal extracts (HE) such as Houttuynia cordata Thunb., Eucommia ulimoides, Plantago asiatica var., Morus alba L., and Ulmus davidiana var., are known to suppress an atopic dermatitis like skin lesions. In this study, to evaluate the cell cytotoxicity effect on L929, HaCaT and HMC-1 cell by the HE, the herbs were extracted with distilled water (at 75 .deg. C) and then the HE mixtures were freeze-dried for 5 days and sterilized with {gamma}-rays. The cytotoxicity was measured by Cell Counting Kit-8 (CCK-8) assay. The result showed that the HE mixtures did not significantly affect cell viability and had no toxicity on the cells. These findings indicate that the HE mixtures can be used as a potential therapeutic agent.

  2. Analysis of Residual DSBs in Ataxia-Telangiectasia Lymphoblast Cells Initiating Apoptosis

    Directory of Open Access Journals (Sweden)

    Teresa Anglada

    2016-01-01

    Full Text Available In order to examine the relationship between accumulation of residual DNA double-strand breaks (DSBs and cell death, we have used a control and an ATM (Ataxia-Telangiectasia Mutated defective cell line, as Ataxia-Telangiectasia (AT cells tend to accumulate residual DSBs at long times after damage infliction. After irradiation, AT cells showed checkpoint impairment and a fraction of cells displayed an abnormal centrosome number and tetraploid DNA content, and this fraction increased along with apoptosis rates. At all times analyzed, AT cells displayed a significantly higher rate of radiation-induced apoptosis than normal cells. Besides apoptosis, 70–85% of the AT viable cells (TUNEL-negative carried ≥10 γH2AX foci/cell, while only 12–27% of normal cells did. The fraction of AT and normal cells undergoing early and late apoptosis were isolated by flow cytometry and residual DSBs were concretely scored in these populations. Half of the γH2AX-positive AT cells undergoing early apoptosis carried ≥10 γH2AX foci/cell and this fraction increased to 75% in late apoptosis. The results suggest that retention of DNA damage-induced γH2AX foci is an indicative of lethal DNA damage, as cells undergoing apoptosis are those accumulating more DSBs. Scoring of residual γH2AX foci might function as a predictive tool to assess radiation-induced apoptosis.

  3. The effect of initial tonicity on freeze/thaw injury to human red cells suspended in solutions of sodium chloride.

    Science.gov (United States)

    Pegg, D E; Diaper, M P

    1991-02-01

    Human red blood cells, suspended in solutions of sodium chloride, have been frozen to temperatures between -2 and -14 degrees C and thawed, and the extent of hemolysis was measured. In parallel experiments, red cells were exposed to similar cycles of change in the composition of the suspending solution, but by dialysis at 21 degrees C. The tonicity of the saline in which the cells were initially suspended was varied between 0.6x isotonic and 4x isotonic; some samples from each experimental treatment were returned to isotonic saline before hemolysis was measured. It was found that the tonicity of the saline used to suspend the cells for the main body of the experiment affected the amount of hemolysis measured: raising the tonicity from 0.6x to 1x to 2x reduced hemolysis, both in the freezing and in the dialysis experiments, whereas raising the tonicity further to 4x reversed that trend. There was little difference between the freeze/thaw and the dialysis treatments for the cells suspended in 1x or 2x saline, whether or not the cells were returned to isotonic conditions. However, the cells suspended in 0.6x saline showed greater damage from freezing and thawing than from the comparable change in the composition of the solution, whether or not they were returned to isotonic conditions. Cells that were suspended in 4x saline and exposed to changes in salt concentration by dialysis showed less hemolysis when they were assayed in the 4x solution than cells that had received the comparable freezing/thaw treatment, but when the experiment included a return to isotonicity, the two treatments gave similar results. Returning the cells to isotonic saline had a negligible affect on the cells in 0.6x and 1x saline, but caused considerable hemolysis in the 2x and 4x samples, more so after dialysis than after freezing and thawing. We conclude that cells suspended in 0.6x and 4x saline behave differently from cells suspended in 1x and 2x saline and hence that cells suspended in a

  4. Ultrasound for initial evaluation and triage of clinically suspicious soft-tissue masses

    International Nuclear Information System (INIS)

    Aim: To evaluate the efficacy of ultrasound as a first-line investigation in patients with a clinical soft-tissue mass. Methods: Three hundred and fifty-eight consecutive patients (155 male, 203 female, mean age 48 years) referred from primary and secondary care with soft-tissue masses underwent ultrasound evaluation. Five radiologists performed ultrasound using a 10-15 MHz linear transducer and recorded the referrer diagnosis, history, lesion size, anatomical location and depth, internal echogenicity, external margins (well-defined rim or infiltrative), and vascularity on power Doppler (absent or present, if present the pattern was listed as either linear or disorganized). A provisional ultrasound diagnosis was made using one of eight categories. Benign categories (categories 1-5) were referred back to a non-sarcoma specialist or original referrer for observation. Indeterminate or possible sarcomas (categories 6-8) were referred for magnetic resonance imaging (MRI) within 14 days. Additionally category 8 lesions were referred to the regional sarcoma service. Institutional and regional database follow-up was performed. Results: Two hundred and eighty-four of the 358 (79%) lesions were classified as benign (categories 1-5). On follow-up 15 of the 284 patients were re-referred but none (284/284) had a malignancy on follow-up (24-30 months). Overall at ultrasound 33 lesions were larger than 5 cm, 42 lesions were deep to deep fascia with 20 showing both features. In this subgroup of 95 patients there were six malignant tumours with the rest benign. Seventy-three of the 358 patients underwent MRI; the results of which indicated that there were 60 benign or non-tumours, 10 possible sarcomas, and three indeterminate lesions. Overall six of 12 (6/358, 1.68% of total patients) lesions deemed to represent possible sarcomas on imaging were sarcomas. Conclusion: Ultrasound is an effective diagnostic triage tool for the evaluation of soft-tissue masses referred from primary

  5. Initial evaluation of the effects of aerosolized Florida red tide toxins (brevetoxins) in persons with asthma.

    Science.gov (United States)

    Fleming, Lora E; Kirkpatrick, Barbara; Backer, Lorraine C; Bean, Judy A; Wanner, Adam; Dalpra, Dana; Tamer, Robert; Zaias, Julia; Cheng, Yung Sung; Pierce, Richard; Naar, Jerome; Abraham, William; Clark, Richard; Zhou, Yue; Henry, Michael S; Johnson, David; Van De Bogart, Gayl; Bossart, Gregory D; Harrington, Mark; Baden, Daniel G

    2005-05-01

    Florida red tides annually occur in the Gulf of Mexico, resulting from blooms of the marine dinoflagellate Karenia brevis. K. brevis produces highly potent natural polyether toxins, known as brevetoxins, that activate voltage-sensitive sodium channels. In experimental animals, brevetoxins cause significant bronchoconstriction. A study of persons who visited the beach recreationally found a significant increase in self-reported respiratory symptoms after exposure to aerosolized Florida red tides. Anecdotal reports indicate that persons with underlying respiratory diseases may be particularly susceptible to adverse health effects from these aerosolized toxins. Fifty-nine persons with physician-diagnosed asthma were evaluated for 1 hr before and after going to the beach on days with and without Florida red tide. Study participants were evaluated with a brief symptom questionnaire, nose and throat swabs, and spirometry approved by the National Institute for Occupational Safety and Health. Environmental monitoring, water and air sampling (i.e., K. brevis, brevetoxins, and particulate size distribution), and personal monitoring (for toxins) were performed. Brevetoxin concentrations were measured by liquid chromatography mass spectrometry, high-performance liquid chromatography, and a newly developed brevetoxin enzyme-linked immunosorbent assay. Participants were significantly more likely to report respiratory symptoms after Florida red tide exposure. Participants demonstrated small but statistically significant decreases in forced expiratory volume in 1 sec, forced expiratory flow between 25 and 75%, and peak expiratory flow after exposure, particularly those regularly using asthma medications. Similar evaluation during nonexposure periods did not significantly differ. This is the first study to show objectively measurable adverse health effects from exposure to aerosolized Florida red tide toxins in persons with asthma. Future studies will examine the possible chronic

  6. Radiosynthesis and initial evaluation of [18F]-FEPPA for PET imaging of peripheral benzodiazepine receptors

    International Nuclear Information System (INIS)

    Introduction: A novel [18F]-radiolabelled phenoxyanilide, [18F]-FEPPA, has been synthesized and evaluated, in vitro and ex vivo, as a potential positron emission tomography imaging agent for the peripheral benzodiazepine receptor (PBR). Methods: [18F]-FEPPA and two other radiotracers for imaging PBR, namely [11C]-PBR28 and [11C]-PBR28-d3, were synthesised and evaluated in vitro and ex vivo as potential PBR imaging agents. Results: [18F]-FEPPA is efficiently prepared in one step from its tosylate precursor and [18F]-fluoride in high radiochemical yields and at high specific activity. FEPPA displayed a Ki of 0.07 nM for PBR in rat mitochondrial membrane preparations and a suitable lipophilicity for brain penetration (log P of 2.99 at pH 7.4). Upon intravenous injection into rats, [18F]-FEPPA showed moderate brain uptake [standard uptake value (SUV) of 0.6 at 5 min] and a slow washout (SUV of 0.35 after 60 min). Highest uptake of radioactivity was seen in the hypothalamus and olfactory bulb, regions previously reported to be enriched in PBR in rat brain. Analysis of plasma and brain extracts demonstrated that [18F]-FEPPA was rapidly metabolized, but no lipophilic metabolites were observed in either preparation and only 5% radioactive metabolites were present in brain tissue extracts. Blocking studies to determine the extent of specific binding of [18F]-FEPPA in rat brain were problematic due to large perturbations in circulating radiotracer and the lack of a reference region. Conclusions: Further evaluation of the potential of [18F]-FEPPA will require the employment of rigorous kinetic models and/or appropriate animal models

  7. Using X-ray computed tomography to evaluate the initial saturation resulting from different saturation procedures

    DEFF Research Database (Denmark)

    Christensen, Britt Stenhøj Baun; Wildenschild, D; Jensen, K.H.

    2006-01-01

    for saturation. Evaluation of the different enhanced saturation techniques was done with Xray computed tomography (CT) and gravimetrically. The use of CT scanning makes it possible to observe the spatial distribution of wetting and non-wetting phases in the porous medium in a non-destructive way. In...... this case the sample was scanned in 1 mm intervals over the height of the 3.5 cm tall sample, providing detailed information on the performance of the different procedures. Five different combinations of the above mentioned saturation procedures were applied to a disturbed silica sand sample. The...

  8. CD133 expression is not selective for tumor initiating or radioresistant cell populations in the CRC line HCT-116

    International Nuclear Information System (INIS)

    The hypothesis of certain subpopulations of cancer cells with stem-cell like characteristics that might be responsible for treatment resistance and recurrence of disease is still challenging and under quite controversial discussion. In most studies, surrogate cell surface antigens such as the 92-110 kDa transmembrane glycoprotein CD133 (human Prominin-1) were labeled to isolate particular small cancer cell populations for studying their tumorigenic potential. In colorectal carcinomas (CRC) for example, a small CD133 positive (CD133+) cell population has recently been described to be enriched for tumor-initiating/cancer stem cells (TIC/CSC) as compared to the CD133 negative (CD133) population. Furthermore, it was documented that the CD133+ subpopulation could exclusively be maintained in culture as spheres under serum-free conditions. Addition of serum resulted in cell differentiation, growth in 2-D and downregulation of CD133 expression. This would imply that established colorectal cancer (CRC) cell lines that have been grown under adherent, serum-supplemented conditions for years should be devoid of CD133+ cells and TIC/CSC, respectively, which seems contradictory to the finding that many CRC lines produce tumors in nude mice models. In order to gain insight into this paradox, we studied the expression of CD133 in numerous established CRC lines under standard culture conditions and chose one particular cell line based on its expression pattern to study the behavior of CD133+ / CD133- subpopulations

  9. An Evaluation of Kinetic Parameters of Cadmium and Copper Biosorption by Immobilized Cells

    Directory of Open Access Journals (Sweden)

    Nelly Georgieva

    2007-10-01

    Full Text Available Bioremediation is the use of living organisms to reduce or eliminate environmental hazards resulting from the accumulation of toxic chemicals and other hazardous wastes. This technology is based on the utilization of microorganisms to transform organic and inorganic compounds. The filamentous yeast Trichosporon cutaneum strain R57, immobilized and free cells was cultivated as batch culture on a liquid medium in the presence of various concentrations of cadmium and copper ions. The simultaneous uptake and accumulation of Cd2+ and Cu2+ ions by Tr. cutaneum cells depending on the initial concentration of Cd2+ and Cu2+ in the medium were studied. The potential use of the free and immobilized cells of Trichosporon cutaneum to remove cadmium and copper ions, from aqueous solutions was evaluated. Two important physicochemical aspects for the evaluation of the sorption process as a unit operation are the equilibrium of sorption and the kinetics. The Cd2+ and Cu2+ ions biosorption capacities of all tested adsorbent were presented as a function of the initial concentration of metal ions within the aqueous biosorption medium. The individual, as well as bicomponent sorption kinetics of copper and cadmium ions by immobilised cells of Trichosporon cutaneum R57 is presented. A second order kinetic model obtains kinetic parameters for the copper and cadmium ions.

  10. Initiation of two ovarian cell lines fromFugu rubripes (Temminck et. Schlegel)

    Institute of Scientific and Technical Information of China (English)

    ZHENG Debin; ZHANG Bo; SONG Wenping; PAN Luqing; MA Chao; XIAO Guangxia

    2015-01-01

    The ovary is an excellent system for studying stem cell renewal and differentiation, which is under the control of ovarian somatic cells. In order to understand oogenesis inFugu rubripes (Temminck et. Schlegel) as a marine fish model of aquaculture importance, we established cell lines called TSOC1 and TSOC2 from a juvenile ovary of this organism. TSOC1 is composed of spindle epithelial-like cells, while the other is cobblestone-like cells. Therefore, TSOC1 and TSOC2 appear to consist of ovarian somatic cells. Growth requirement condition was investigated including temperature, concentration of FBS and pH. Significant fluorescent signals were observed after TSOC1 and TSOC2 cells were transfected with pEGFP-N3 vector, indicating its potential utility for genetic manipulation such as gene function studies. It is shown that these cell lines are effective for infection by the turbot reddish body iridovirus and flounder lymphosystis disease virus as evidenced by the appearance of cytopathic effect and virus propagation in the virus-infected cells, and most convincingly, the observation of viral particles by electron microscopy, demonstrating that TSOC1 and TSOC2 are suitable to study interactions between virus and host cells. It is believed that TSOC1 and TSOC2 will be useful tools to study sex-related events and interactions between primordial germ cells and oogonia cells during oogenesis. Therefore, establishment of ovary cell lines fromFugu rubripes seems to be significant for those research areas.

  11. Automated Work Packages Prototype: Initial Design, Development, and Evaluation. Light Water Reactor Sustainability Program

    International Nuclear Information System (INIS)

    The goal of the Automated Work Packages (AWP) project is to demonstrate how to enhance work quality, cost management, and nuclear safety through the use of advanced technology. The work described in this report is part of the digital architecture for a highly automated plant project of the technical program plan for advanced instrumentation, information, and control (II&C) systems technologies. This report addresses the DOE Milestone M2LW-15IN0603112: Describe the outcomes of field evaluations/demonstrations of the AWP prototype system and plant surveillance and communication framework requirements at host utilities. A brief background to the need for AWP research is provided, then two human factors field evaluation studies are described. These studies focus on the user experience of conducting a task (in this case a preventive maintenance and a surveillance test) while using an AWP system. The remaining part of the report describes an II&C effort to provide real time status updates to the technician by wireless transfer of equipment indications and a dynamic user interface.

  12. A knitted garment using intarsia technique for Heart Rate Variability biofeedback: Evaluation of initial prototype.

    Science.gov (United States)

    Abtahi, F; Ji, G; Lu, K; Rödby, K; Seoane, F

    2015-01-01

    Heart rate variability (HRV) biofeedback is a method based on paced breathing at specific rate called resonance frequency by giving online feedbacks from user respiration and its effect on HRV. Since the HRV is also influence by different factors like stress and emotions, stress related to an unfamiliar measurement device, cables and skin electrodes may cover the underling effect of such kind of intervention. Wearable systems are usually considered as intuitive solutions which are more familiar to the end-user and can help to improve usability and hence reducing the stress. In this work, a prototype of a knitted garment using intarsia technique is developed and evaluated. Results show the satisfactory level of quality for Electrocardiogram and thoracic electrical bioimpedance i.e. for respiration monitoring as a part of HRV biofeedback system. Using intarsia technique and conductive yarn for making the connection instead of cables will reduce the complexity of fabrication in textile production and hence reduce the final costs in a final commercial product. Further development of garment and Android application is ongoing and usability and efficiency of final prototype will be evaluated in detail. PMID:26736953

  13. An initial evaluation of the Convex SPP-1000 for Earth and space science applications.

    Science.gov (United States)

    Sterling, T. L.; Savarese, D. F.; Merkey, P. R.; Gardner, J. P.

    1995-10-01

    The Convex SPP-1000 is the most recent of the new generation of Scalable Parallel Computing systems being offered commercially. The SPP-1000 is distinguished by incorporating the first commercial version of directory based cache coherence mechanisms and the emerging Scalable Coherent Interface protocol to achieve a true global shared memory capability. Pairs of HP PA-RISC processors are combined in clusters of 8 processors using a cross-bar switch. Up to 16 clusters are interconnected using 4 ring networks in parallel with a distributed global cache. To evaluate this new system in a Beta test environment, the Goddard Space Flight Center conducted three classes of operational experiments with an emphasis on applications related to Earth and space science. A cluster was tested as a platform for executing a multiple program workload exploiting job-stream level parallelism. Synthetic programs were run to measure overhead costs of barrier, fork-join, and message passing synchronization primitives. A key problem for Earth and space science studies is gravitational N-body simulation of solar systems to galactic clusters. An efficient tree-code version of this problem was run to reveal scaling properties of the system and to measure the overall efficiency. This paper presents the experimental results and findings of this study and provides the earliest published evaluation of this new scalable architecture.

  14. Evaluation of the State Energy Conservation Program from program initiation to September 1978. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Heller, James N.; Grossmann, John R.; Shochet, Susan; Bresler, Joel; Duggan, Noreene

    1980-03-01

    The State Energy Conservation Program was established in 1975 to promote energy conservation and to help states develop and implement their own conservation programs. Base (5) and supplemental (3) programs required states to implement programs including: mandatory thermal-efficiency standards and insulation requirements for new and renovated buildings; mandatory lighting efficiency standards for public buildings; mandatory standards and policies affecting the procurement practices of the state and its political subdivisions; program measures to promote the availability and use of carpools, vanpools, and public transportation; a traffic law or regulation which permits a right turn-on-red; and procedures to carry out a continuing public education effort to increase awareness of energy conservation; procedures which promote effective coordination among local, state, and Federal energy conservation programs; and procedures for carrying out energy audits on buildings and industrial plants. All 50 states and Puerto Rico, Guam, the Virgin Islands, American Samoa, and the District of Columbia participated in the program. The total 1980 energy savings projected by the states is about 5.9 quadrillion Btu's or about 7% of the DOE projected 1980 baseline consumption of just under 83 quads. The detailed summary is presented on the following: information the SECP evaluation; DOE response to the SECP; DOE's role in the program management process; the effectiveness of the states in managing the SECP; the status of program measure implementation; innovative state energy conservation programs; and the evaluation methodology.

  15. Information fusion performance evaluation for motion imagery data using mutual information: initial study

    Science.gov (United States)

    Grieggs, Samuel M.; McLaughlin, Michael J.; Ezekiel, Soundararajan; Blasch, Erik

    2015-06-01

    As technology and internet use grows at an exponential rate, video and imagery data is becoming increasingly important. Various techniques such as Wide Area Motion imagery (WAMI), Full Motion Video (FMV), and Hyperspectral Imaging (HSI) are used to collect motion data and extract relevant information. Detecting and identifying a particular object in imagery data is an important step in understanding visual imagery, such as content-based image retrieval (CBIR). Imagery data is segmented and automatically analyzed and stored in dynamic and robust database. In our system, we seek utilize image fusion methods which require quality metrics. Many Image Fusion (IF) algorithms have been proposed based on different, but only a few metrics, used to evaluate the performance of these algorithms. In this paper, we seek a robust, objective metric to evaluate the performance of IF algorithms which compares the outcome of a given algorithm to ground truth and reports several types of errors. Given the ground truth of a motion imagery data, it will compute detection failure, false alarm, precision and recall metrics, background and foreground regions statistics, as well as split and merge of foreground regions. Using the Structural Similarity Index (SSIM), Mutual Information (MI), and entropy metrics; experimental results demonstrate the effectiveness of the proposed methodology for object detection, activity exploitation, and CBIR.

  16. Evaluation of esophageal peristalsis in patients with esophageal tumors. Initial experience with cine MR imaging

    International Nuclear Information System (INIS)

    We evaluated esophageal peristalsis in patients with esophageal tumors by cine MR using steady-state free precession (SSFP) sequence and correlated the alteration of the esophageal peristalsis with clinical symptoms and tumor stages. Thirteen patients with pathologically proven esophageal tumors, including 12 esophageal cancers and one submucosal leiomyoma, underwent cine MRI using true fast imaging with steady precession (trueFISP) sequence, which is one SSFP sequence, after contrast-enhanced MR scanning for clinical purposes. A total of 120 serial images were obtained within 60 s through the plane along the long axis of the esophagus while patients chewed gum. The serial trueFISP images were evaluated for the presence, frequency, speed of progression, and passage of peristalsis through the tumor. The data from cine MRI were compared with clinical symptoms and tumor stages. Peristalsis was clearly identified in all patients. Seven patients with complete interruption of peristalsis had dysphagia; one with partially impaired peristalsis could intake solid foods with discomfort; and two with partially impaired peristalsis and three with preserved peristalsis remained asymptomatic. Patients with complete or partial interruption of peristalsis had Stage T3 or T4 esophageal cancer. In conclusion, trueFISP cine MR imaging enables direct visualization of esophageal peristalsis in relation to esophageal tumors. Complete interruption of peristalsis causes dysphagia, whereas partial interruption of and preserved peristalsis usually do not cause digestive problems. Interruption of peristalsis may indicate impaired muscle function caused by invasion of advanced esophageal cancers. (author)

  17. A head-mounted display system for augmented reality: Initial evaluation for interventional MRI

    International Nuclear Information System (INIS)

    Purpose: To discuss the technical details of a head mounted display with an augmented reality (AR) system and to describe a first pre-clinical evaluation in interventional MRI. Method: The AR system consists of a video-see-through head mounted display (HMD), mounted with a mini video camera for tracking and a stereo pair of mini cameras that capture live images of the scene. The live video view of the phantom/patient is augmented with graphical representations of anatomical structures from MRI image data and is displayed on the HMD. The application of the AR system with interventional MRI was tested using a MRI data set of the head and a head phantom. Results: The HMD enables the user to move around and observe the scene dynamically from various viewpoints. Within a short time the natural hand-eye coordination can easily be adapted to the slightly different view. The 3D perception is based on stereo and kinetic depth cues. A circular target with a diameter of 0.5 square centimeter was hit in 19 of 20 attempts. In a first evaluation the MRI image data augmented reality scene of a head phantom allowed good planning and precise simulation of a puncture. Conclusion: The HMD in combination with AR provides a direct, intuitive guidance for interventional MR procedures. (orig.)

  18. Automated Work Packages Prototype: Initial Design, Development, and Evaluation. Light Water Reactor Sustainability Program

    Energy Technology Data Exchange (ETDEWEB)

    Oxstrand, Johanna Helene [Idaho National Lab. (INL), Idaho Falls, ID (United States); Al Rashdan, Ahmad [Idaho National Lab. (INL), Idaho Falls, ID (United States); Le Blanc, Katya Lee [Idaho National Lab. (INL), Idaho Falls, ID (United States); Bly, Aaron Douglas [Idaho National Lab. (INL), Idaho Falls, ID (United States); Agarwal, Vivek [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-07-01

    The goal of the Automated Work Packages (AWP) project is to demonstrate how to enhance work quality, cost management, and nuclear safety through the use of advanced technology. The work described in this report is part of the digital architecture for a highly automated plant project of the technical program plan for advanced instrumentation, information, and control (II&C) systems technologies. This report addresses the DOE Milestone M2LW-15IN0603112: Describe the outcomes of field evaluations/demonstrations of the AWP prototype system and plant surveillance and communication framework requirements at host utilities. A brief background to the need for AWP research is provided, then two human factors field evaluation studies are described. These studies focus on the user experience of conducting a task (in this case a preventive maintenance and a surveillance test) while using an AWP system. The remaining part of the report describes an II&C effort to provide real time status updates to the technician by wireless transfer of equipment indications and a dynamic user interface.

  19. Alport syndrome: significance of gingival biopsy in the initial diagnosis and periodontal evaluation after renal transplantation

    Directory of Open Access Journals (Sweden)

    Hilal Uslu Toygar

    2009-12-01

    Full Text Available Alport Syndrome (AS is an important hereditary disorder affecting the glomerular basement membrane. Diagnosis of AS is based on the presence of hematuric nephropathy, renal failure, hearing loss, ocular abnormalities and changes in the glomerular basement membrane of the lamina densa. The aims of this case report were to show the changes in the gingival tissues in a patient with AS under therapy with cyclosporin-A after renal transplantation and to discuss the possible role of type IV collagen in gingival basal lamina as an alternative approach for the diagnosis of AS. A 20-year-old male patient with AS underwent periodontal therapy including a series of gingivectomy surgeries. Gingival samples obtained during the second surgery were examined histopathologically and by transmission electron microscopy for further pathological examination. Gingivectomy procedures have been performed every 6 months over the last 4 years. The excessive and fibrous gingival enlargements resulted in migration of the anterior teeth, but no alveolar bone loss occurred. This is the first report to demonstrate the possible changes in the gingival tissues caused by AS. It is suggested that gingival biopsy can be an initial diagnostic tool instead of renal or skin biopsies. Proper dental and periodontal care and regular visits to the dentist could provide limited gingival hyperplasia to patients with AS.

  20. Evaluating the Initialization Methods of Wavelet Networks for Hyperspectral Image Classification

    Science.gov (United States)

    Hsu, Pai-Hui

    2016-06-01

    The idea of using artificial neural network has been proven useful for hyperspectral image classification. However, the high dimensionality of hyperspectral images usually leads to the failure of constructing an effective neural network classifier. To improve the performance of neural network classifier, wavelet-based feature extraction algorithms can be applied to extract useful features for hyperspectral image classification. However, the extracted features with fixed position and dilation parameters of the wavelets provide insufficient characteristics of spectrum. In this study, wavelet networks which integrates the advantages of wavelet-based feature extraction and neural networks classification is proposed for hyperspectral image classification. Wavelet networks is a kind of feed-forward neural networks using wavelets as activation function. Both the position and the dilation parameters of the wavelets are optimized as well as the weights of the network during the training phase. The value of wavelet networks lies in their capabilities of optimizing network weights and extracting essential features simultaneously for hyperspectral images classification. In this study, the influence of the learning rate and momentum term during the network training phase is presented, and several initialization modes of wavelet networks were used to test the performance of wavelet networks.

  1. Initial Evaluation of Engine Combustion Network Injectors with X-Ray Diagnostics

    International Nuclear Information System (INIS)

    A significant hurdle in the understanding of diesel sprays is the sensitivity of such sprays to the detailed geometry of the spray nozzle. This sensitivity hampers the comparison of results from spray measurements by different research groups, even if the groups measure nozzles with the same nominal geometry. Moreover, these differences make the comparison and validation of different diagnostic techniques problematic. To remove this source of uncertainty from diesel spray measurements, a collaboration of several research groups has formed to measure a common set of injectors under identical conditions under the auspices of Sandia National Laboratorys Engine Combustion Network. The current work describes the initial measurement of these injectors and the sprays created by these injectors using the x-ray diagnostics available at the Advanced Photon Source. X-ray phase-enhanced imaging is used to perform time-resolved, in situ measurements of injector pintle motion. In addition to these measurements, x-ray radiography measurements of the sprays from these injectors will be performed to better understand the near-nozzle fuel mass distribution in these sprays.

  2. Clinician performed resuscitative ultrasonography for the initial evaluation and resuscitation of trauma

    Directory of Open Access Journals (Sweden)

    Gillman Lawrence M

    2009-08-01

    Full Text Available Abstract Background Traumatic injury is a leading cause of morbidity and mortality in developed countries worldwide. Recent studies suggest that many deaths are preventable if injuries are recognized and treated in an expeditious manner – the so called 'golden hour' of trauma. Ultrasound revolutionized the care of the trauma patient with the introduction of the FAST (Focused Assessment with Sonography for Trauma examination; a rapid assessment of the hemodynamically unstable patient to identify the presence of peritoneal and/or pericardial fluid. Since that time the use of ultrasound has expanded to include a rapid assessment of almost every facet of the trauma patient. As a result, ultrasound is not only viewed as a diagnostic test, but actually as an extension of the physical exam. Methods A review of the medical literature was performed and articles pertaining to ultrasound-assisted assessment of the trauma patient were obtained. The literature selected was based on the preference and clinical expertise of authors. Discussion In this review we explore the benefits and pitfalls of applying resuscitative ultrasound to every aspect of the initial assessment of the critically injured trauma patient.

  3. Second Line of Defense Megaports Initiative Operational Testing and Evaluation Plan - Kingston Container Terminal, Port of Kingston, Jamaica

    Energy Technology Data Exchange (ETDEWEB)

    Deforest, Thomas J.; VanDyke, Damon S.

    2012-03-01

    Operational Testing and Evaluation Plan - Kingston Container Terminal, Port of Kingston, Jamaica was written for the Second Line of Defense Megaports Initiative. The purpose of the Operational Testing and Evaluation (OT&E) phase of the project is to prepare for turnover of the Megaports system supplied by U.S. Department of Energy/National Nuclear Security Administration (DOE/NNSA) located at the Kingston Container Terminal (KCT) of the Port of Kingston, Jamaica to the Government of Jamaica (GOJ). Activities conducted during the OT&E phase must demonstrate that the Megaports system can be operated effectively in real time by Jamaica Customs and KCT personnel to the satisfaction of the DOE/NNSA. These activities will also determine if the Megaports system, as installed and accepted, is performing according to the Megaports Program objectives such that the system is capable of executing the mission of the Second Line of Defense Megaports Initiative. The OT&E phase of the project also provides an opportunity to consider potential improvements to the system and to take remedial action if performance deficiencies are identified during the course of evaluation. Changes to the system should be considered under an appropriate change-control process. DOE/NNSA will determine that OT&E is complete by examining whether the Megaports system is performing as intended and that the GOJ is fully capable of operating the system independently without continued onsite support from the U.S. team.

  4. Forskolin and the meiosis inducing substance synergistically initiate meiosis in fetal male germ cells

    DEFF Research Database (Denmark)

    Byskov, A G; Fenger, M; Westergaard, L;

    1993-01-01

    We have shown that Meiosis Inducing Substance (MIS) and forskolin synergistically and dose dependently induce meiosis in germ cells of cultured fetal mouse testes. We used a bioassay which consists of fetal mouse testes and ovaries cultured for 6 days. In this study MIS media are spent culture...... fixed, squashed, and DNA-stained. In these preparations germ cells and somatic cells can be distinguished, and the number of germ cells in the different stages of meiosis is counted as is the number of somatic cells in mitosis. MIS activity is defined to be present in a medium when meiosis is induced in...... male germ cells during culture. We found that MIS media as well as forskolin induced meiosis in fetal male germ cells in a dose-dependent manner. In addition, MIS media and forskolin acted synergistically by inducing meiosis. Female germ cells seem to be unaffected by the various culture media. These...

  5. Evaluation of the Redesign of an Undergraduate Cell Biology Course

    Science.gov (United States)

    McEwen, Laura April; Harris, dik; Schmid, Richard F.; Vogel, Jackie; Western, Tamara; Harrison, Paul

    2009-01-01

    This article offers a case study of the evaluation of a redesigned and redeveloped laboratory-based cell biology course. The course was a compulsory element of the biology program, but the laboratory had become outdated and was inadequately equipped. With the support of a faculty-based teaching improvement project, the teaching team redesigned the…

  6. Initial performance evaluation of major components in the head-end reprocessing solids handling system

    International Nuclear Information System (INIS)

    The General Atomic cold head-end reprocessing pilot plant has been built to demonstrate the feasibility of the proposed commercial reprocessing flowsheet, in particular its integrated operation. This integration is accomplished in part by the solids handling system, which is designed to provide transfer of material at required rates between different steps in the process and to provide the required surge capacity. The major components of the solids handling system have been tested in order to verify or upgrade the design. The components described here are: inlet filters, conveying lines, bunkers, in-bunker filters, blowers, level sensors, feeders, and weigh cells. By and large, the equipment has performed as expected. Feeding of the various materials in the system has received considerable attention, and several improvements were necessary. The system is now equipped to perform its function of serving the needs of the other unit operations in the pilot plant

  7. Role of lymphocyte-specific protein tyrosine kinase (LCK) in the expansion of glioma-initiating cells by fractionated radiation

    International Nuclear Information System (INIS)

    Research highlights: → Activation of Lymphocyte-specific protein tyrosine kinase (LCK) is involved in the fractionated radiation-induced expansion of glioma stem-like cells. → Inhibition of LCK prevents acquisition of fractionated radiation-induced resistance to chemotherapeutic treatment. → LCK activity is critical for the maintenance of self-renewal in glioma stem-like cells. -- Abstract: Brain cancers frequently recur or progress as focal masses after treatment with ionizing radiation. Radiation used to target gliomas may expand the cancer stem cell population and enhance the aggressiveness of tumors; however, the mechanisms underlying the expansion of cancer stem cell population after radiation have remained unclear. In this study, we show that LCK (lymphocyte-specific protein tyrosine kinase) is involved in the fractionated radiation-induced expansion of the glioma-initiating cell population and acquisition of resistance to anticancer treatments. Fractionated radiation caused a selective increase in the activity of LCK, a Src family non-receptor tyrosine kinase. The activities of other Src family kinases Src, Fyn, and Lyn were not significantly increased. Moreover, knockdown of LCK expression with a specific small interfering RNA (siRNA) effectively blocked fractionated radiation-induced expansion of the CD133+ cell population. siRNA targeting of LCK also suppressed fractionated radiation-induced expression of the glioma stem cell marker proteins CD133, Nestin, and Musashi. Expression of the known self-renewal-related proteins Notch2 and Sox2 in glioma cells treated with fractionated radiation was also downregulated by LCK inhibition. Moreover, siRNA-mediated knockdown of LCK effectively restored the sensitivity of glioma cells to cisplatin and etoposide. These results indicate that the non-receptor tyrosine kinase LCK is critically involved in fractionated radiation-induced expansion of the glioma-initiating cell population and decreased cellular

  8. Social Pedagogy in the UK today: findings from evaluations of training and development initiatives

    Directory of Open Access Journals (Sweden)

    Claire Cameron

    2015-12-01

    Full Text Available Since 2007, workplace based social pedagogic intervention has been taking place in the UK. Until that point, social pedagogy was largely unknown within children’s services practice or training. This paper synthesises findings from 10 evaluation studies that examined social pedagogic intervention in the form of training and development activity in children’s residential care, foster care and related services. The findings are presented in relation to four types of impact: on the ‘trainees’; on the learning organisation; on children; and on the wider context. Findings are positive across all four types of impact, but especially so in relation to ‘trainees’ and children. Social pedagogy appears to validate and reframe practice as reflective, relational and enjoyable which helps children to thrive in public care settings. One key factor in the positive impact of social pedagogy training may be the experiential learning style adopted by trainers. 

  9. Second Line of Defense Megaports Initiative Operational Testing and Evaluation Plan Colon Container Terminal (CCT) Panama

    Energy Technology Data Exchange (ETDEWEB)

    Newhouse, Robert N.

    2010-01-01

    Report on the Operational Testing and Evaluation to validate and baseline an operable system that meets the Second Line of Defense (SLD) mission requirements. An SLD system is defined as the detection technology and associated equipment, the system operators from the host country, the standard operating procedures (SOPs), and other elements such as training and maintenance which support long-term system sustainment. To this end, the activities conducted during the OT&E phase must demonstrate that the Megaports System can be operated effectively in real-time by Panama Direccion General de Aduanas (DGA Panama Customs) personnel to the standards of the U.S. Department of Energy/National Nuclear Security Administration (DOE/NNSA).

  10. Novel Scanning Lens Instrument for Evaluating Fresnel Lens Performance: Equipment Development and Initial Results (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Herrero, R.; Miller, D. C.; Kurtz, S. R.; Anton, I.; Sala, G.

    2013-07-01

    A system dedicated to the optical transmittance characterization of Fresnel lenses has been developed at NREL, in collaboration with the UPM. The system quantifies the optical efficiency of the lens by generating a performance map. The shape of the focused spot may also be analyzed to understand change in the lens performance. The primary instrument components (lasers and CCD detector) have been characterized to confirm their capability for performing optical transmittance measurements. Measurements performed on SoG and PMMA lenses subject to a variety of indoor conditions (e.g., UV and damp heat) identified differences in the optical efficiency of the evaluated lenses, demonstrating the ability of the Scanning Lens Instrument (SLI) to distinguish between the aged lenses.

  11. A Modified NK Cell Degranulation Assay Applicable for Routine Evaluation of NK Cell Function

    Science.gov (United States)

    Shabrish, Snehal; Gupta, Maya; Madkaikar, Manisha

    2016-01-01

    Natural killer (NK) cells play important role in innate immunity against tumors and viral infections. Studies show that lysosome-associated membrane protein-1 (LAMP-1, CD107a) is a marker for degranulation of NK and cytotoxic T cells and its expression is a sensitive marker for the cytotoxic activity determination. The conventional methods of determination of CD107a on NK cells involve use of peripheral blood mononuclear cells (PBMC) or pure NK cells and K562 cells as stimulants. Thus, it requires large volume of blood sample which is usually difficult to obtain in pediatric patients and patients with cytopenia and also requires specialized laboratory for maintaining cell line. We have designed a flow cytometric assay to determine CD107a on NK cells using whole blood, eliminating the need for isolation of PBMC or isolate NK cells. This assay uses phorbol-12-myristate-13-acetate (PMA) and calcium ionophore (Ca2+-ionophore) instead of K562 cells for stimulation and thus does not require specialized cell culture laboratory. CD107a expression on NK cells using modified NK cell degranulation assay compared to the conventional assay was significantly elevated (p < 0.0001). It was also validated by testing patients diagnosed with familial hemophagocytic lymphohistiocytosis (FHL) with defect in exocytosis. This assay is rapid, cost effective, and reproducible and requires significantly less volume of blood which is important for clinical evaluation of NK cells. PMID:27413758

  12. Microwave imaging for tissue assessment: initial evaluation in multitarget tissue-equivalent phantoms.

    Science.gov (United States)

    Meaney, P M; Paulsen, K D; Hartov, A; Crane, R K

    1996-09-01

    A prototype microwave imaging system is evaluated for its ability to recover two-dimensional (2-D) electrical property distributions under transverse magnetic (TM) illumination using multitarget tissue equivalent phantoms. Experiments conducted in a surrounding lossy saline tank demonstrate that simultaneous recovery of both the real and imaginary components of the electrical property distribution is possible using absolute imaging procedures over a frequency range of 300-700 MHz. Further, image reconstructions of embedded tissue-equivalent targets are found to be quantitative not only with respect to geometrical factors such as object size and location but also electrical composition. Quantitative assessments based on full-width half-height criteria reveal that errors in diameter estimates of reconstructed targets are less than 10 mm in all cases, whereas, positioning errors are less than 1 mm in single object experiments but degrade to 4-10 mm when multiple targets are present. Recovery of actual electrical properties is found to be frequency dependent for the real and imaginary components with background values being typically within 10-20% of their correct size and embedded object having similar accuracies as a percentage of the electrical contrast, although errors as high as 50% can occur. The quantitative evaluation of imaging performance has revealed potential advantages in a two-tiered receiver antenna configuration whose measured field values are more sensitive to target region changes than the typical tomographic type of approach which uses reception sites around the full target region perimeter. This measurement strategy has important implications for both the image reconstruction algorithm where there is a premium on minimizing problem size without sacrificing image quality and the hardware system design which seeks to economize on the amount of measured data required for quantitative image reconstruction while maximizing its sensitivity to target

  13. Positron Emission Tomography (PET) Evaluation After Initial Chemotherapy and Radiation Therapy Predicts Local Control in Rhabdomyosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Dharmarajan, Kavita V., E-mail: dharmark@mskcc.org [Departments of Radiation Oncology, Pediatric Oncology, and Nuclear Medicine, Memorial Sloan-Kettering, New York, New York (United States); Wexler, Leonard H.; Gavane, Somali; Fox, Josef J.; Schoder, Heiko; Tom, Ashlyn K.; Price, Alison N.; Meyers, Paul A.; Wolden, Suzanne L. [Departments of Radiation Oncology, Pediatric Oncology, and Nuclear Medicine, Memorial Sloan-Kettering, New York, New York (United States)

    2012-11-15

    Purpose: 18-fluorodeoxyglucose positron emission tomography (PET) is already an integral part of staging in rhabdomyosarcoma. We investigated whether primary-site treatment response characterized by serial PET imaging at specific time points can be correlated with local control. Patients and Methods: We retrospectively examined 94 patients with rhabdomyosarcoma who received initial chemotherapy 15 weeks (median) before radiotherapy and underwent baseline, preradiation, and postradiation PET. Baseline PET standardized uptake values (SUVmax) and the presence or absence of abnormal uptake (termed PET-positive or PET-negative) both before and after radiation were examined for the primary site. Local relapse-free survival (LRFS) was calculated according to baseline SUVmax, PET-positive status, and PET-negative status by the Kaplan-Meier method, and comparisons were tested with the log-rank test. Results: The median patient age was 11 years. With 3-year median follow-up, LRFS was improved among postradiation PET-negative vs PET-positive patients: 94% vs 75%, P=.02. By contrast, on baseline PET, LRFS was not significantly different for primary-site SUVmax {<=}7 vs >7 (median), although the findings suggested a trend toward improved LRFS: 96% for SUVmax {<=}7 vs 79% for SUVmax >7, P=.08. Preradiation PET also suggested a statistically insignificant trend toward improved LRFS for PET-negative (97%) vs PET-positive (81%) patients (P=.06). Conclusion: Negative postradiation PET predicted improved LRFS. Notably, 77% of patients with persistent postradiation uptake did not experience local failure, suggesting that these patients could be closely followed up rather than immediately referred for intervention. Negative baseline and preradiation PET findings suggested statistically insignificant trends toward improved LRFS. Additional study may further understanding of relationships between PET findings at these time points and outcome in rhabdomyosarcoma.

  14. Positron Emission Tomography (PET) Evaluation After Initial Chemotherapy and Radiation Therapy Predicts Local Control in Rhabdomyosarcoma

    International Nuclear Information System (INIS)

    Purpose: 18-fluorodeoxyglucose positron emission tomography (PET) is already an integral part of staging in rhabdomyosarcoma. We investigated whether primary-site treatment response characterized by serial PET imaging at specific time points can be correlated with local control. Patients and Methods: We retrospectively examined 94 patients with rhabdomyosarcoma who received initial chemotherapy 15 weeks (median) before radiotherapy and underwent baseline, preradiation, and postradiation PET. Baseline PET standardized uptake values (SUVmax) and the presence or absence of abnormal uptake (termed PET-positive or PET-negative) both before and after radiation were examined for the primary site. Local relapse-free survival (LRFS) was calculated according to baseline SUVmax, PET-positive status, and PET-negative status by the Kaplan-Meier method, and comparisons were tested with the log-rank test. Results: The median patient age was 11 years. With 3-year median follow-up, LRFS was improved among postradiation PET-negative vs PET-positive patients: 94% vs 75%, P=.02. By contrast, on baseline PET, LRFS was not significantly different for primary-site SUVmax ≤7 vs >7 (median), although the findings suggested a trend toward improved LRFS: 96% for SUVmax ≤7 vs 79% for SUVmax >7, P=.08. Preradiation PET also suggested a statistically insignificant trend toward improved LRFS for PET-negative (97%) vs PET-positive (81%) patients (P=.06). Conclusion: Negative postradiation PET predicted improved LRFS. Notably, 77% of patients with persistent postradiation uptake did not experience local failure, suggesting that these patients could be closely followed up rather than immediately referred for intervention. Negative baseline and preradiation PET findings suggested statistically insignificant trends toward improved LRFS. Additional study may further understanding of relationships between PET findings at these time points and outcome in rhabdomyosarcoma.

  15. Evaluating alternative stem cell hypotheses for adultcorneal epithelial maintenance

    Institute of Scientific and Technical Information of China (English)

    John D West; Natalie J Dorà; Natalie J Dorà,

    2015-01-01

    In this review we evaluate evidence for three differenthypotheses that explain how the corneal epitheliumis maintained. The limbal epithelial stem cell (LESC)hypothesis is most widely accepted. This proposes thatstem cells in the basal layer of the limbal epithelium,at the periphery of the cornea, maintain themselvesand also produce transient (or transit) amplifying cells(TACs). TACs then move centripetally to the centre ofthe cornea in the basal layer of the corneal epitheliumand also replenish cells in the overlying suprabasallayers. The LESCs maintain the corneal epitheliumduring normal homeostasis and become more active torepair significant wounds. Second, the corneal epithelialstem cell (CESC) hypothesis postulates that, duringnormal homeostasis, stem cells distributed throughoutthe basal corneal epithelium, maintain the tissue.According to this hypothesis, LESCs are present in thelimbus but are only active during wound healing. We alsoconsider a third possibility, that the corneal epithelium ismaintained during normal homeostasis by proliferationof basal corneal epithelial cells without any input fromstem cells. After reviewing the published evidence,we conclude that the LESC and CESC hypotheses areconsistent with more of the evidence than the thirdhypothesis, so we do not consider this further. The LESCand CESC hypotheses each have difficulty accountingfor one main type of evidence so we evaluate the twokey lines of evidence that discriminate between them.Finally, we discuss how lineage-tracing experimentshave begun to resolve the debate in favour of theLESC hypothesis. Nevertheless, it also seems likely thatsome basal corneal epithelial cells can act as long-termprogenitors if limbal stem cell function is compromised.Thus, this aspect of the CESC hypothesis may have alasting impact on our understanding of corneal epithelialmaintenance, even if it is eventually shown that stemcells are restricted to the limbus as proposed by the

  16. Fluorodeoxyglucose positron emission tomography in the initial staging of germ cell tumours

    Energy Technology Data Exchange (ETDEWEB)

    Hain, S.F.; O' Doherty, M.J. [Clinical PET Centre, Guy' s and St Thomas' Hospitals, London (United Kingdom); Timothy, A.R.; Leslie, M.D.; Partridge, S.E. [Dept. of Clinical Oncology, Guy' s and St Thomas' Hospitals, London (United Kingdom); Huddart, R.A. [Dept. of Radiotherapy and Oncology, Royal Marsden, Surrey (United Kingdom)

    2000-05-01

    Testicular cancer is a rare tumour with the potential for cure at diagnosis. It is important, however, to identify those patients with metastases at presentation so as to ensure that the optimum treatment strategy is employed. Many criteria have been used to try to place patients into high- or low-risk groups, with variable success. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has the potential to identify active disease and thereby influence further management. Here we report on a retrospective study of the use of FDG-PET in the detection of metastatic testicular carcinoma at diagnosis. Thirty-one patients [13 with seminoma and 18 with non-seminomatous germ cell tumours (13 teratomas, 5 mixed)] were staged by FDG-PET scanning. The imaging was performed using a Siemens ECAT 951 scanner. All results were assessed on the basis of histology or clinical follow-up. FDG-PET scan identified metastatic disease in ten and was negative in 16; there were no false-positives and five false-negatives. There were six patients in whom FDG-PET was negative and computed tomography was regarded as suspicious but follow-up was inconclusive. The positive predictive value was 100%. The negative predictive value was 76% or 91%, depending on whether the aforementioned six cases were regarded as true-negatives or false-negatives. It may be concluded that FDG-PET is capable of detecting metastatic disease at diagnosis that is not identified by other imaging techniques. These preliminary results are sufficient to suggest that a large prospective study should be performed to evaluate the role of FDG-PET in primary staging of disease. (orig.)

  17. Poly(A) binding protein abundance regulates eukaryotic translation initiation factor 4F assembly in human cytomegalovirus-infected cells.

    Science.gov (United States)

    McKinney, Caleb; Perez, Cesar; Mohr, Ian

    2012-04-10

    By commandeering cellular translation initiation factors, or destroying those dispensable for viral mRNA translation, viruses often suppress host protein synthesis. In contrast, cellular protein synthesis proceeds in human cytomegalovirus (HCMV)-infected cells, forcing viral and cellular mRNAs to compete for limiting translation initiation factors. Curiously, inactivating the host translational repressor 4E-BP1 in HCMV-infected cells stimulates synthesis of the cellular poly(A) binding protein (PABP), significantly increasing PABP abundance. Here, we establish that new PABP synthesis is translationally controlled by the HCMV-encoded UL38 mammalian target of rapamycin complex 1-activator. The 5' UTR within the mRNA encoding PABP contains a terminal oligopyrimidine (TOP) element found in mRNAs, the translation of which is stimulated in response to mitogenic, growth, and nutritional stimuli, and proteins encoded by TOP-containing mRNAs accumulated in HCMV-infected cells. Furthermore, UL38 expression was necessary and sufficient to regulate expression of a PABP TOP-containing reporter. Remarkably, preventing the rise in PABP abundance by RNAi impaired eIF4E binding to eIF4G, thereby reducing assembly of the multisubunit initiation factor eIF4F, viral protein production, and replication. This finding demonstrates that viruses can increase host translation initiation factor concentration to foster their replication and defines a unique mechanism whereby control of PABP abundance regulates eIF4F assembly. PMID:22431630

  18. RALDH2, the enzyme for retinoic acid synthesis, mediates meiosis initiation in germ cells of the female embryonic chickens.

    Science.gov (United States)

    Yu, Minli; Yu, Ping; Leghari, Imdad H; Ge, Chutian; Mi, Yuling; Zhang, Caiqiao

    2013-02-01

    Meiosis is a process unique to the differentiation of germ cells and exhibits sex-specific in timing. Previous studies showed that retinoic acid (RA) as the vitamin A metabolite is crucial for controlling Stra8 (Stimulated by retinoic acid gene 8) expression in the gonad and to initiate meiosis; however, the mechanism by which retinoid-signaling acts has remained unclear. In the present study, we investigated the role of the enzyme retinaldehyde dehydrogenase 2 (RALDH2) which catalyzes RA synthesizes by initiating meiosis in chicken ovarian germ cells. Meiotic germ cells were first detected at day 15.5 in chicken embryo ovary when the expression of synaptonemal complex protein 3 (Scp3) and disrupted meiotic cDNA 1 homologue (Dmc1) became elevated, while Stra8 expression was specifically up-regulated at day 12.5 before meiosis onset. It was observed from the increase in Raldh2 mRNA expression levels and decreases in Cyp26b1 (the enzyme for RA catabolism) expression levels during meiosis that requirement for RA accumulation is essential to sustain meiosis. This was also revealed by RA stimulation of the cultured ovaries with the initiation of meiosis response, and the knocking down of the Raldh2 expression during meiosis, leading to abolishment of RA-dependent action. Altogether, these studies indicate that RA synthesis by the enzyme RALDH2 and signaling through its receptor is crucial for meiosis initiation in chicken embryonic ovary. PMID:22733143

  19. Evaluation of 309 environmental chemicals using a mouse embryonic stem cell adherent cell differentiation and cytotoxicity assay.

    Directory of Open Access Journals (Sweden)

    Kelly J Chandler

    Full Text Available The vast landscape of environmental chemicals has motivated the need for alternative methods to traditional whole-animal bioassays in toxicity testing. Embryonic stem (ES cells provide an in vitro model of embryonic development and an alternative method for assessing developmental toxicity. Here, we evaluated 309 environmental chemicals, mostly food-use pesticides, from the ToxCast™ chemical library using a mouse ES cell platform. ES cells were cultured in the absence of pluripotency factors to promote spontaneous differentiation and in the presence of DMSO-solubilized chemicals at different concentrations to test the effects of exposure on differentiation and cytotoxicity. Cardiomyocyte differentiation (α,β myosin heavy chain; MYH6/MYH7 and cytotoxicity (DRAQ5™/Sapphire700™ were measured by In-Cell Western™ analysis. Half-maximal activity concentration (AC₅₀ values for differentiation and cytotoxicity endpoints were determined, with 18% of the chemical library showing significant activity on either endpoint. Mining these effects against the ToxCast Phase I assays (∼500 revealed significant associations for a subset of chemicals (26 that perturbed transcription-based activities and impaired ES cell differentiation. Increased transcriptional activity of several critical developmental genes including BMPR2, PAX6 and OCT1 were strongly associated with decreased ES cell differentiation. Multiple genes involved in reactive oxygen species signaling pathways (NRF2, ABCG2, GSTA2, HIF1A were strongly associated with decreased ES cell differentiation as well. A multivariate model built from these data revealed alterations in ABCG2 transporter was a strong predictor of impaired ES cell differentiation. Taken together, these results provide an initial characterization of metabolic and regulatory pathways by which some environmental chemicals may act to disrupt ES cell growth and differentiation.

  20. Lessons from Library Power: Enriching Teaching and Learning. Final Report of the Evaluation of the National Library Power Initiative, an Initiative of the DeWitt Wallace-Reader's Digest Fund.

    Science.gov (United States)

    Zweizig, Douglas L.; Hopkins, Dianne McAfee

    This book presents the results of an evaluation of Library Power, an initiative of the DeWitt Wallace-Reader's Digest Fund that provided support for school library development in 19 communities. Following an introductory chapter, the chapters are organized around key questions of the evaluation. Chapters 2 through 4 address the implementation of…

  1. Development and initial evaluation of a spectral microdensitometer for analysing radiochromic films

    International Nuclear Information System (INIS)

    Radiation dose deposited on a radiochromic film is considered as a dose image. A precise image extraction system with commensurate capabilities is required to measure the transmittance of the image and translate it to radiation dose. This paper describes the development of a spectral microdensitometer which has been designed to achieve this goal under the conditions of (a) the linearity and sensitivity of the dose response curve of the radiochromic film being highly dependent on the wavelength of the analysing light, and (b) the inherent high spatial resolution of the film. The microdensitometer consists of a monochromator which provides an analysing light of variable wavelength, a film tray on a high-precision scanning stage, a transmission microscope coupled to a thermoelectrically cooled CCD camera, a microcomputer and corresponding interfaces. The measurement of the transmittance of the radiochromic film is made at the two absorption peaks with maximum sensitivities. The high spatial resolution of the instrument, of the order of micrometres, is achieved through the use of the microscope combined with a measure-and-step technique to cover the whole film. The performance of the instrument in regard to the positional accuracy, system reproducibility and dual-peak film calibration was evaluated. The results show that the instrument fulfils the design objective of providing a precise image extraction system for radiochromic films with micrometre spatial resolution and sensitive dose response

  2. Development and initial evaluation of a spectral microdensitometer for analysing radiochromic films

    Energy Technology Data Exchange (ETDEWEB)

    Lee, K Y [Department of Optometry and Radiography, Hong Kong Polytechnic University, Hong Kong (China); Fung, K L [Department of Optometry and Radiography, Hong Kong Polytechnic University, Hong Kong (China); Kwok, C S [Department of Radioimmunotherapy, City of Hope National Medical Centre, Duarte, CA 91010 (United States)

    2004-11-21

    Radiation dose deposited on a radiochromic film is considered as a dose image. A precise image extraction system with commensurate capabilities is required to measure the transmittance of the image and translate it to radiation dose. This paper describes the development of a spectral microdensitometer which has been designed to achieve this goal under the conditions of (a) the linearity and sensitivity of the dose response curve of the radiochromic film being highly dependent on the wavelength of the analysing light, and (b) the inherent high spatial resolution of the film. The microdensitometer consists of a monochromator which provides an analysing light of variable wavelength, a film tray on a high-precision scanning stage, a transmission microscope coupled to a thermoelectrically cooled CCD camera, a microcomputer and corresponding interfaces. The measurement of the transmittance of the radiochromic film is made at the two absorption peaks with maximum sensitivities. The high spatial resolution of the instrument, of the order of micrometres, is achieved through the use of the microscope combined with a measure-and-step technique to cover the whole film. The performance of the instrument in regard to the positional accuracy, system reproducibility and dual-peak film calibration was evaluated. The results show that the instrument fulfils the design objective of providing a precise image extraction system for radiochromic films with micrometre spatial resolution and sensitive dose response.

  3. Transcription Factors and Medium Suitable for Initiating the Differentiation of Human-Induced Pluripotent Stem Cells to the Hepatocyte Lineage.

    Science.gov (United States)

    Tomizawa, Minoru; Shinozaki, Fuminobu; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

    2016-09-01

    Transcription factors and culture media were investigated to determine the condition to initiate the differentiation of human-induced pluripotent stem (iPS) cells most efficiently. The expression of genes in human adult liver was compared with that in 201B7 cells (iPS cells) using cDNA microarray analysis. Episomal plasmids expressing transcription factors were constructed. 201B7 cells were transfected with the episomal plasmids and cultured in ReproFF (feeder-free media maintaining pluripotency), Leibovitz-15 (L15), William's E (WE), or Dulbecco's modified Eagle medium/Nutrient F-12 Ham (DF12) for 7 days. RNA was isolated and subjected to real-time quantitative PCR to analyze the expression of alpha-feto protein (AFP) and albumin. cDNA microarray analysis revealed 16 transcription factors that were upregulated in human adult liver relative to that in 201B7 cells. Episomal plasmids expressing these 16 genes were transfected into 201B7 cells. CCAAT/enhancer-binding protein alpha (CEBPA), CCAAT/enhancer-binding protein beta (CEBPB), forkhead box A1 (FOXA1), and forkhead box A3 (FOXA3) up-regulated AFP and down-regulated Nanog. These four genes were further analyzed. The expression of AFP and albumin was the highest in 201B7 cells transfected with the combination of CEBPA, CEBPB, FOXA1, and FOXA3 and cultured in WE. The combination of CEBPA, CEBPB, FOXA1, and FOXA3 was suitable for 201B7 cells to initiate differentiation to the hepatocyte lineage and WE was the most suitable medium for culture after transfection. J. Cell. Biochem. 117: 2001-2009, 2016. © 2016 Wiley Periodicals, Inc. PMID:26773721

  4. American Fuel Cell Bus Project Evaluation. Second Report

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, Leslie [National Renewable Energy Lab. (NREL), Golden, CO (United States); Post, Matthew [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2015-09-01

    This report presents results of the American Fuel Cell Bus (AFCB) Project, a demonstration of fuel cell electric buses operating in the Coachella Valley area of California. The prototype AFCB was developed as part of the Federal Transit Administration's (FTA's) National Fuel Cell Bus Program. Through the non-profit consortia CALSTART, a team led by SunLine Transit Agency and BAE Systems developed a new fuel cell electric bus for demonstration. SunLine added two more AFCBs to its fleet in 2014 and another in 2015. FTA and the AFCB project team are collaborating with the U.S. Department of Energy (DOE) and DOE's National Renewable Energy Laboratory to evaluate the buses in revenue service. This report summarizes the performance results for the buses through June 2015.

  5. Relation between both oxidative and metabolic-osmotic cell damages and initial injury severity in bombing casualties

    Directory of Open Access Journals (Sweden)

    Vučeljić Marina

    2006-01-01

    Full Text Available Background/Aim. We have recently reported the development of oxidative cell damages in bombing casualties within a very early period after the initial injury. The aim of this study, was to investigate malondialdehyde (MDA, as an indicator of lipid peroxidation, and osmolal gap (OG, as a good indicator of metabolic cell damages and to assess their relationship with the initial severity of the injury in bombing casualties. Methods. The study included the males (n = 52, injured during the bombing with the Injury Severity Score (ISS ranging from 3 to 66. The whole group of casualties was devided into a group of less severely (ISS < 25, n = 24 and a group of severely (ISS ≥ 26, n = 28 injured males. The uninjured volunteers (n = 10 were the controls. Osmolality, MDA, sodium, glucose, urea, creatinine, total bilirubin and total protein levels were measured in the venous blood, sampled daily, within a ten-day period. Results. In both groups of casualties, MDA and OG levels increased, total protein levels decreased, while other parameters were within the control limits. MDA alterations correlated with ISS (r = 0.414, p < 0.01, while a statistically significant correlation between OG and ISS was not obtained. Interestingly, in spite of some differences in MDA and OG trends, at the end of the examined period they were at the similar level in both groups. Conclusion. The initial oxidative damages of the cellular membrane with intracellular metabolic disorders contributed to the gradual development of metabolic-osmotic damages of cells, which, consequently caused the OG increase. In the bombing casualties, oxidative cell damages were dependent on the initial injury severity, while metabolic-osmotic cell damages were not.

  6. An Interactive 3D Virtual Anatomy Puzzle for Learning and Simulation - Initial Demonstration and Evaluation.

    Science.gov (United States)

    Messier, Erik; Wilcox, Jascha; Dawson-Elli, Alexander; Diaz, Gabriel; Linte, Cristian A

    2016-01-01

    To inspire young students (grades 6-12) to become medical practitioners and biomedical engineers, it is necessary to expose them to key concepts of the field in a way that is both exciting and informative. Recent advances in medical image acquisition, manipulation, processing, visualization, and display have revolutionized the approach in which the human body and internal anatomy can be seen and studied. It is now possible to collect 3D, 4D, and 5D medical images of patient specific data, and display that data to the end user using consumer level 3D stereoscopic display technology. Despite such advancements, traditional 2D modes of content presentation such as textbooks and slides are still the standard didactic equipment used to teach young students anatomy. More sophisticated methods of display can help to elucidate the complex 3D relationships between structures that are so often missed when viewing only 2D media, and can instill in students an appreciation for the interconnection between medicine and technology. Here we describe the design, implementation, and preliminary evaluation of a 3D virtual anatomy puzzle dedicated to helping users learn the anatomy of various organs and systems by manipulating 3D virtual data. The puzzle currently comprises several components of the human anatomy and can be easily extended to include additional organs and systems. The 3D virtual anatomy puzzle game was implemented and piloted using three display paradigms - a traditional 2D monitor, a 3D TV with active shutter glass, and the DK2 version Oculus Rift, as well as two different user interaction devices - a space mouse and traditional keyboard controls. PMID:27046584

  7. Evaluation of a novel Seldinger-needle for computed tomography guided interventions: initial experiences

    International Nuclear Information System (INIS)

    To evaluate a new Seldinger puncture device for computed tomography-guided interventions under difficult conditions, to analyze applicability, and to investigate assets and drawbacks. From November 2007 to March 2008, we performed CT-guided interventions in 16 patients (7 women, 9 men; mean age 62 years old) using a new 20G-Seldinger needle (Sika-Med, Wiehl, Germany). This novel needle serves as a guide for many different interventional devices due to a guide wire welded on the proximal needle end. It allows continuous application of anesthesia via four tiny holes at the distal needle end until the region of interest is reached. Each intervention was subject to difficult interventional conditions. The indications for intervention were drainage (n = 7), Trucut biopsy of tumor (n = 8) and radiofrequency ablation (n = 1). Handling, success, advantages, drawbacks, complications and patient tolerance were noted after each procedure. A pain scale from 1 - 10 was used to grade the pain level during the intervention. All interventions were performed successfully and no severe complications were observed. Patient tolerance was very good resulting in a mean pain score of 2 ± 1. Regions with dangerous and difficult access were successfully reached with the new Seldinger needle in 15 of 16 cases by dilatation of the puncture tract and continuous administration of local anesthesia via the system. Furthermore, different devices such as Trucut systems and a drainage catheter were able to be inserted without complication via the needle. With a proximal removable luer-lock connection, liquid material was able to be aspirated in six cases. Under difficult interventional conditions, the use of a Seldinger needle as a reliable technique for CT-guided interventions can provide a safe and successful procedure. (orig.)

  8. A new method for determination of Most Likely Initiation Points and the evaluation of Digital Terrain Model scale in terrain stability mapping

    Directory of Open Access Journals (Sweden)

    P. Tarolli

    2006-04-01

    Full Text Available Physically-based models have been used previously to map areas of potential instability where shallow landslides may initiate. Here we introduce a new approach for determining the Most Likely Initiation Points (MLIP for landslides. We identify the location with critical (lowest stability index from a terrain stability model on each downslope path from ridge to valley. The SINMAP Stability Index (SI was applied with this method. Only potential initiation points less than a threshold are considered to avoid identification of stable locations on downslope paths that do not contain any unstable locations. Mapped or observed landslides are often used to evaluate the effectiveness of model derived terrain stability maps, but a problem with these observations is that they may demarcate the entire landslide scar, including run out zones, rather than just initiation locations. Comparing such observations to SI does not provide a meaningful way to assess the effectiveness of the SI map because the demarcated area may include considerable area with stable SI values. In this paper we suggest using the relative density of MLIP locations within and outside demarcated landslide areas to assess the discriminating capability of a SI map. This approach was tested using landslides mapped from aerial photographs and airborne laser altimetry (LIDAR derived elevation data for a small basin located in the Northeastern Region of Italy. Digital Terrain Models (DTMs were derived from the LIDAR data for a range of grid cell sizes (from 2 to 50 m and SI and MLIP evaluated for each. We found that the direct comparison of SI within and outside of landslides was not effective. However when MLIP was used we found appreciable differences between the density of MLIP points within and outside mapped landslides with ratios as large as three or more with the highest ratios for a DTM grid cell size of 10 m. This demonstrated the utility of the MLIP approach to quantifying the

  9. Differential replication of two porcine parvovirus strains in bovine cell lines ensues from initial DNA processing and NS1 expression.

    Science.gov (United States)

    Fernandes, Sandra; Boisvert, Maude; Szelei, Jozsef; Tijssen, Peter

    2014-04-01

    Porcine parvovirus (PPV) is a small DNA virus with restricted coding capacity. The 5 kb genome expresses three major non-structural proteins (NS1, NS2 and SAT), and two structural proteins (VP1 and VP2). These few viral proteins are pleiotropic and interact with cellular components throughout viral replication. In this regard, very few cell lines have been shown to replicate the virus efficiently. Cell lines were established from a primary culture of bovine cells that allowed allotropic variants of PPV to be distinguished. Three cell lines were differentially sensitive to infection by two prototype PPV strains, NADL-2 and Kresse. In the first cell line (D10), infection was restricted early in the infectious cycle and was not productive. Infection of the second cell line (G11) was 1000 times less efficient with the NADL-2 strain compared with porcine cells, while production of infectious virus of the Kresse strain was barely detectable. Restriction points in these cells were the initial generation of DNA replication intermediates and NS1 production. Infection with chimeras between NADL-2 and Kresse showed that residues outside the previously described allotropic determinant were also partially responsible for the restriction to Kresse replication in G11 cells. F4 cells were permissive to both strains, although genome replication and infectious virus production were lower than in the porcine cells used for comparison. These results highlight the dependent nature of parvovirus tropism on host factors and suggest that cells from a non-host origin can fully support a productive infection by both strains. PMID:24347493

  10. Test and Approval Center for Fuel Cell and Hydrogen Technologies: Phase I. Initiation:Final report

    OpenAIRE

    2012-01-01

    Fuel cells and hydrogen technologies hold the potential for decreasing emissions of greenhouse gases and air pollutants, for facilitating the increased use of renewable energy sources with high efficiencies and thereby contributing to the establishment of a sustainable energy system and the mitigation of the human-caused global warming. Fuel cells (in particular solid oxide fuel cells) produce electricity and heat at higher efficiencies than conventional power plants. They emit less pollutant...

  11. Successful Reconstruction of Tooth Germ with Cell Lines Requires Coordinated Gene Expressions from the Initiation Stage

    OpenAIRE

    Yasuhiro Tomooka; Akihiko Komine

    2012-01-01

    Tooth morphogenesis is carried out by a series of reciprocal interactions between the epithelium and mesenchyme in embryonic germs. Previously clonal dental epithelial cell (epithelium of molar tooth germ (emtg)) lines were established from an embryonic germ. They were odontogenic when combined with a dental mesenchymal tissue, although the odontogenesis was quantitatively imperfect. To improve the microenvironment in the germs, freshly isolated dental epithelial cells were mixed with cells o...

  12. Forskolin and the meiosis inducing substance synergistically initiate meiosis in fetal male germ cells

    DEFF Research Database (Denmark)

    Byskov, A G; Fenger, M; Westergaard, L;

    1993-01-01

    We have shown that Meiosis Inducing Substance (MIS) and forskolin synergistically and dose dependently induce meiosis in germ cells of cultured fetal mouse testes. We used a bioassay which consists of fetal mouse testes and ovaries cultured for 6 days. In this study MIS media are spent culture...... male germ cells during culture. We found that MIS media as well as forskolin induced meiosis in fetal male germ cells in a dose-dependent manner. In addition, MIS media and forskolin acted synergistically by inducing meiosis. Female germ cells seem to be unaffected by the various culture media. These...

  13. Evaluation of high-energy lithium thionyl chloride primary cells

    Science.gov (United States)

    Frank, H. A.

    1980-01-01

    An advanced commercial primary lithium cell (LiSoCl2) was evaluated in order to establish baseline data for improved lithium batteries for aerospace applications. The cell tested had nominal capacity of 6 Ah. Maximum energy density at low rates (less than C/30, where C is the cell capacity in amp-hrs and 30 corresponds to a 30 hr discharge time) was found to be near 300 Wh/kg. An equation which predicts the operating voltage of these cells as a function of current and state of charge is presented. Heat generation rates of these cells were determined as a function of current in a calorimeter. It was found that heat rates could be theoretically predicted with some degree of accuracy at currents less than 1 amp or the C/6 rate. No explosions were observed in the cells during the condition of overdischarge or reversal nor during high rate discharge. It was found, however, that the cells can vent when overdischarge currents are greater than C/30 and when discharge rates are greater than 1.5C.

  14. Bmi1 overexpression in the cerebellar granule cell lineage of mice affects cell proliferation and survival without initiating medulloblastoma formation

    Directory of Open Access Journals (Sweden)

    Hourinaz Behesti

    2013-01-01

    BMI1 is a potent inducer of neural stem cell self-renewal and neural progenitor cell proliferation during development and in adult tissue homeostasis. It is overexpressed in numerous human cancers – including medulloblastomas, in which its functional role is unclear. We generated transgenic mouse lines with targeted overexpression of Bmi1 in the cerebellar granule cell lineage, a cell type that has been shown to act as a cell of origin for medulloblastomas. Overexpression of Bmi1 in granule cell progenitors (GCPs led to a decrease in cerebellar size due to decreased GCP proliferation and repression of the expression of cyclin genes, whereas Bmi1 overexpression in postmitotic granule cells improved cell survival in response to stress by altering the expression of genes in the mitochondrial cell death pathway and of Myc and Lef-1. Although no medulloblastomas developed in ageing cohorts of transgenic mice, crosses with Trp53−/− mice resulted in a low incidence of medulloblastoma formation. Furthermore, analysis of a large collection of primary human medulloblastomas revealed that tumours with a BMI1high TP53low molecular profile are significantly enriched in Group 4 human medulloblastomas. Our data suggest that different levels and timing of Bmi1 overexpression yield distinct cellular outcomes within the same cellular lineage. Importantly, Bmi1 overexpression at the GCP stage does not induce tumour formation, suggesting that BMI1 overexpression in GCP-derived human medulloblastomas probably occurs during later stages of oncogenesis and might serve to enhance tumour cell survival.

  15. Eukaryotic Translation Initiation Factor 3a (eIF3a) Promotes Cell Proliferation and Motility in Pancreatic Cancer.

    Science.gov (United States)

    Wang, Shu Qian; Liu, Yu; Yao, Min Ya; Jin, Jing

    2016-10-01

    Identifying a target molecule that is crucially involved in pancreatic tumor growth and metastasis is necessary in developing an effective treatment. The study aimed to investigate the role of the eukaryotic translation initiation factor 3a (eIF3a) in the cell proliferation and motility in pancreatic cancer. Our data showed that the expression of eIF3a was upregulated in pancreatic ductal adenocarcinoma as compared with its expression in normal pancreatic tissues. Knockdown of eIF3a by a specific shRNA caused significant decreases in cell proliferation and clonogenic abilities in pancreatic cancer SW1990 and Capan-1 cells. Consistently, the pancreatic cancer cell growth rates were also impaired in xenotransplanted mice. Moreover, wound-healing assay showed that depletion of eIF3a significantly slowed down the wound recovery processes in SW1990 and Capan-1 cells. Transwell migration and invasion assays further showed that cell migration and invasion abilities were significantly inhibited by knockdown of eIF3a in SW1990 and Capan-1 cells. Statistical analysis of eIF3a expression in 140 cases of pancreatic ductal adenocarcinoma samples revealed that eIF3a expression was significantly associated with tumor metastasis and TNM staging. These analyses suggest that eIF3a contributes to cell proliferation and motility in pancreatic ductal adenocarcinoma. PMID:27550487

  16. Unenhanced multidetector CT (CT KUB) in the initial imaging of suspected acute renal colic: evaluating a new service

    Energy Technology Data Exchange (ETDEWEB)

    Chowdhury, F.U. [Departments of Clinical Radiology, Leeds Teaching Hospitals, Leeds (United Kingdom); Kotwal, S. [Urology, Leeds Teaching Hospitals, Leeds (United Kingdom); Raghunathan, G.; Wah, T.M. [Departments of Clinical Radiology, Leeds Teaching Hospitals, Leeds (United Kingdom); Joyce, A. [Urology, Leeds Teaching Hospitals, Leeds (United Kingdom); Irving, H.C. [Departments of Clinical Radiology, Leeds Teaching Hospitals, Leeds (United Kingdom)], E-mail: henry.irving@leedsth.nhs.uk

    2007-10-15

    Aim: To evaluate a new imaging pathway for the investigation of patients presenting with suspected acute renal colic. Materials and methods: A retrospective review of 500 consecutive cases of suspected acute renal colic was undertaken to evaluate the initial results of a new imaging pathway introduced at our institution, which completely replaced the intravenous urogram (IVU) with unenhanced multidetector CT (CT KUB). Results: The positive rate for urolithiasis was 44% (221/500), the negative rate 46% (229/500) and the rate of other significant findings was 12% (59/500). Female patients had a low positive rate compared with male patients (27.5 versus 57.5%; p < 0.001). Urological intervention was required in 28% (61/221) and these patients had a larger average stone size (6.6 versus 3.7 mm; p < 0.001) and the stone was located more proximally. Out-of-hours imaging was performed in 37% (186/500), and these patients had a higher positive rate (52 versus 40%; p < 0.001). Other findings included a wide range of acute non-urological conditions. Conclusion: The feasibility of replacing the acute IVU with CT KUB in the initial assessment of suspected acute renal colic was demonstrated in the present study. The technique enables rapid diagnosis of urolithiasis, stratification of patients likely to proceed to urological intervention, and prompt diagnosis of a variety of other acute pathological conditions.

  17. Mechanism of initial attachment of cells derived from human bone to commonly used prosthetic materials during cell culture.

    Science.gov (United States)

    Howlett, C R; Evans, M D; Walsh, W R; Johnson, G; Steele, J G

    1994-02-01

    The suitability of polymeric biomaterials as surfaces for the attachment and growth of cells has often been investigated in cell culture. In this study the contribution that serum fibronectin (Fn) or vitronectin (Vn) make to the attachment and spreading of cells cultured from explanted human bone (bone-derived cells) during the first 90 min of culture was determined for metallic and ceramic surfaces. The requirement for Fn or Vn for attachment and spreading of bone-derived cells onto stainless steel 316 (SS), titanium (Ti) and alumina (Al2O3) and to polyethyleneterephthalate (PET) was directly tested by selective removal of Fn or Vn from the serum prior to addition to the culture medium. Attachment and spreading of bone-derived cells onto SS, Ti and Al2O3 surfaces were reduced by 73-83% when the cells were seeded in medium containing serum from which the Vn had been removed. Cell attachment and spreading on these surfaces when seeded in medium containing Fn-depleted serum (which contained Vn) were not reduced to the same extent as in the medium containing Vn-depleted serum. The bone-derived cells failed to attach to the surfaces to the same extent when seeded in medium containing serum depleted of both Vn and Fn. Our results show that for human bone-derived cells, the attachment and spreading of cells onto SS, Ti and Al2O3 as well as PET during the first 90 min of a cell culture attachment assay are a function of adsorption of serum Vn onto the surface. PMID:7515290

  18. Inhibition of replicon initiation and DNA elongation in Chinese hamster ovary cells by treatment at 45.5 degrees C

    International Nuclear Information System (INIS)

    Heat treatment of Chinese hamster ovary cells at 45.5 degrees C for 15 minutes resulted in the inhibition of both the replicon initiation and the DNA elongation processes. Analysis of the DNA made after treatment showed that for up to 30 minutes after hyperthermia, there was a significant increase (45-80% above control level) in the amount of labeled DNA less than or equal to 40S in size and having a distinct peak of 20S. Therefore, elongation of 20S molecules into larger molecules was inhibited or slowed down. These small molecules did not accumulate when recovery times were longer than 30 minutes. The DNA made after 120 and 240 minutes postheat incubation was larger than control size and indicated that, although replicon initiation was still inhibited, elongation between replicons into 120S molecules could take place. However, their subsequent elongation into parental-size molecules was inhibited. The same delay in DNA elongation seen in cells examined immediately after treatment was still observed in cells heated and allowed to recover for 30 minutes. Also, after 30 minutes of recovery, heated cells still had more newly synthesized DNA in the single-stranded fraction than did control cells, which indicates that DNA elongation within a replicon is delayed for at least 30 minutes after heating. Furthermore, at 4 hours after heating, the inhibition of elongation of clusters of replicons into parental molecules prevailed

  19. Initial work on electron beam welding of 1.3 GHz single cell prototype cavity and their process validation efforts

    International Nuclear Information System (INIS)

    RRCAT has initiated the development of 1.3 GHz (TESLA shape) Superconducting (SC) single cell cavity. In this paper we present the development effort in electron beam (EB) welding and process validation efforts done during prototype development. Niobium being expensive material, initial efforts have been made to go through the complete manufacturing cycle using dummy (aluminum) material. We will present manufacturing of rolled beam pipe with the help of dedicated precision tube rolling machine, development of welding fixtures and EB welding of prototype single cell aluminium cavity using industry support. Development of various welding parameters and weld shrinkage estimation is also described. In order to prepare qualification procedure, frequency of half-cell was measured before and after EB welding to know the frequency shift associated with weld shrinkage. We will also report the frequency simulation done using ANSYS for different stages of single cell cavity manufacturing. Further our plans to manufacture and test single cell cavity in Niobium (Nb) in association with Inter-University Accelerator Centre (IUAC), New Delhi are also presented. (author)

  20. The two chromosomes of Vibrio cholerae are initiated at different time points in the cell cycle

    DEFF Research Database (Denmark)

    Rasmussen, Tue; Jensen, Rasmus Bugge; Skovgaard, Ole

    2007-01-01

    The bacterium Vibrio cholerae, the cause of the diarrhoeal disease cholera, has its genome divided between two chromosomes, a feature uncommon for bacteria. The two chromosomes are of different sizes and different initiator molecules control their replication independently. Using novel methods for...... approximately the same time and the average number of replication origins per cell is higher for chromosome I than for chromosome II. Analysis of cell-cycle parameters shows that chromosome replication and segregation is exceptionally fast in V. cholerae. The divided genome and delayed replication of chromosome...

  1. Biopsy versus FDG PET/CT in the initial evaluation of bone marrow involvement in pediatric lymphoma patients

    International Nuclear Information System (INIS)

    The objective is to assess the role of 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/CT versus bone marrow biopsy (BMB) in the initial evaluation of bone marrow (BM) involvement in pediatric lymphoma patients. Fifty-four pediatric patients with pathologically proven lymphoma [31 Hodgkin's disease (HD), 23 non-Hodgkin's lymphoma (NHL)] were included in this study. All patients had soft tissue biopsy and BMB and had FDG PET/CT scans within 2 weeks of biopsy. Among the 31 HD patients, FDG PET/CT revealed positive BM involvement in 4 patients, while BMB revealed BM involvement in 2 patients who were also positive on FDG PET/CT imaging. Among the 23 NHL patients, FDG PET/CT revealed positive BM involvement in 8 patients, while biopsy revealed BM involvement in 5 patients on initial studies (4 of them were also positive on FDG PET/CT, and 1 was BMB positive but was negative on FDG PET/CT), plus 1 false-negative BMB study initially but positive on repeat biopsy after FDG PET/CT. The overall sensitivity of detecting BM involvement by lymphoma was 92 and 54% (p < 0.05) for FDG PET/CT and BMB, respectively. It is noted that there were more positive BMB findings in patients with abnormal FDG activities seen in the biopsy sites on PET/CT. Our study demonstrates that FDG PET/CT has high sensitivity and accuracy and a substantial complementary value to BMB in the initial diagnosis of pediatric lymphoma, and should be employed as a first-line study. (orig.)

  2. Biopsy versus FDG PET/CT in the initial evaluation of bone marrow involvement in pediatric lymphoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Gang; Chamroonrat, Wichana; Torigian, Drew A.; Alavi, Abass [Hospital of the University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States); Chen, Wengen [University of Maryland Medical Center, Department of Diagnostic Radiology and Nuclear Medicine, Baltimore, MD (United States); Zhuang, Hongming [Children' s Hospital of Philadelphia, Philadelphia, PA (United States)

    2011-08-15

    The objective is to assess the role of {sup 18}F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/CT versus bone marrow biopsy (BMB) in the initial evaluation of bone marrow (BM) involvement in pediatric lymphoma patients. Fifty-four pediatric patients with pathologically proven lymphoma [31 Hodgkin's disease (HD), 23 non-Hodgkin's lymphoma (NHL)] were included in this study. All patients had soft tissue biopsy and BMB and had FDG PET/CT scans within 2 weeks of biopsy. Among the 31 HD patients, FDG PET/CT revealed positive BM involvement in 4 patients, while BMB revealed BM involvement in 2 patients who were also positive on FDG PET/CT imaging. Among the 23 NHL patients, FDG PET/CT revealed positive BM involvement in 8 patients, while biopsy revealed BM involvement in 5 patients on initial studies (4 of them were also positive on FDG PET/CT, and 1 was BMB positive but was negative on FDG PET/CT), plus 1 false-negative BMB study initially but positive on repeat biopsy after FDG PET/CT. The overall sensitivity of detecting BM involvement by lymphoma was 92 and 54% (p < 0.05) for FDG PET/CT and BMB, respectively. It is noted that there were more positive BMB findings in patients with abnormal FDG activities seen in the biopsy sites on PET/CT. Our study demonstrates that FDG PET/CT has high sensitivity and accuracy and a substantial complementary value to BMB in the initial diagnosis of pediatric lymphoma, and should be employed as a first-line study. (orig.)

  3. Activated Alveolar Epithelial Cells Initiate Fibrosis through Secretion of Mesenchymal Proteins

    OpenAIRE

    Yang, Jibing; Wheeler, Sarah E.; Velikoff, Miranda; Kleaveland, Kathryn R.; LaFemina, Michael J.; Frank, James A.; Chapman, Harold A.; Christensen, Paul J; Kim, Kevin K.

    2013-01-01

    Fibrosis is characterized by accumulation of activated fibroblasts and pathological deposition of fibrillar collagens. Activated fibroblasts overexpress matrix proteins and release factors that promote further recruitment of activated fibroblasts, leading to progressive fibrosis. The contribution of epithelial cells to this process remains unknown. Epithelium-directed injury may lead to activation of epithelial cells with phenotypes and functions similar to activated fibroblasts. Prior report...

  4. Using magnetic resonance imaging to evaluate dendritic cell-based vaccination.

    Directory of Open Access Journals (Sweden)

    Peter M Ferguson

    Full Text Available Cancer immunotherapy with antigen-loaded dendritic cell-based vaccines can induce clinical responses in some patients, but further optimization is required to unlock the full potential of this strategy in the clinic. Optimization is dependent on being able to monitor the cellular events that take place once the dendritic cells have been injected in vivo, and to establish whether antigen-specific immune responses to the tumour have been induced. Here we describe the use of magnetic resonance imaging (MRI as a simple, non-invasive approach to evaluate vaccine success. By loading the dendritic cells with highly magnetic iron nanoparticles it is possible to assess whether the injected cells drain to the lymph nodes. It is also possible to establish whether an antigen-specific response is initiated by assessing migration of successive rounds of antigen-loaded dendritic cells; in the face of a successfully primed cytotoxic response, the bulk of antigen-loaded cells are eradicated on-route to the node, whereas cells without antigen can reach the node unchecked. It is also possible to verify the induction of a vaccine-induced response by simply monitoring increases in draining lymph node size as a consequence of vaccine-induced lymphocyte trapping, which is an antigen-specific response that becomes more pronounced with repeated vaccination. Overall, these MRI techniques can provide useful early feedback on vaccination strategies, and could also be used in decision making to select responders from non-responders early in therapy.

  5. BC Transit Fuel Cell Bus Project Evaluation Results: Second Report

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Post, M.

    2014-09-01

    Second report evaluating a fuel cell electric bus (FCEB) demonstration led by British Columbia Transit (BC Transit) in Whistler, Canada. BC Transit is collaborating with the California Air Resources Board and the U.S. Department of Energy's National Renewable Energy Laboratory to evaluate the buses in revenue service. NREL published its first report on the demonstration in February 2014. This report is an update to the previous report; it covers 3 full years of revenue service data on the buses from April 2011 through March 2014 and focuses on the final experiences and lessons learned.

  6. Influence of Macromer Molecular Weight and Chemistry on Poly(β-amino ester) Network Properties and Initial Cell Interactions

    OpenAIRE

    Brey, Darren M.; Erickson, Isaac; Burdick, Jason A.

    2008-01-01

    A library of photocrosslinkable poly(β-amino ester)s (PBAEs) was recently synthesized to expand the number of degradable polymers that can be screened and developed for a variety of biological applications. In this work, the influence of variations in macromer chemistry and macromer molecular weight (MMW) on network reaction behavior, overall bulk properties, and cell interactions were investigated. The MMW was controlled through alterations in the initial diacrylate to amine ratio (≥1) durin...

  7. Parents' Experiences of Receiving the Initial Positive Newborn Screening (NBS) Result for Cystic Fibrosis and Sickle Cell Disease

    OpenAIRE

    Chudleigh, Jane; Buckingham, Sarah; Dignan, Jo; O'Driscoll, Sandra; Johnson, Kemi; Rees, David; Wyatt, Hilary; Metcalfe, Alison

    2016-01-01

    The clinical advantages of the newborn screening programme (NBS) in the UK are well described in the literature. However, there has been little exploration of the psychosocial impact on the family. This study followed the principles of grounded theory to explore parents' experiences of receiving the initial positive NBS result for their child with cystic fibrosis (CF) or sickle cell disease (SCD). Semi-structured, qualitative interviews were conducted with 22 parents (12 mothers and 10 father...

  8. Towards an Appropriate Beamforming Scheme for Initial Cell Discovery in mmW 5G Cellular Networks

    OpenAIRE

    Abbas, Waqas bin; Zorzi, Michele

    2016-01-01

    Beamforming is an essential requirement to combat high pathloss and to improve signal-to-noise ratio during initial cell discovery in future millimeter wave cellular networks. The choice of an appropriate beamforming is directly coupled with its energy consumption. The energy consumption is even of more concern at a battery limited mobile station (MS). In this work, we provide an energy consumption based comparison of different beamforming schemes while considering both a low power and a high...

  9. Estimation of the initial slope of the cell survival curve after irradiation from micronucleus frequency in cytokinesis-blocked cells

    International Nuclear Information System (INIS)

    We have already reported that the α/β ratio of the cell survival curve could be estimated from the micronucleus frequency in cytokinesis-blocked cells treated with cytochalasin-B after irradiation. In this paper, we investigate the direct relationship between the α value and the appearance of micronuclei. Cells of the SCCVII, RIF-1, EMT6, V-79, CHO, HeLa and human esophageal cancer cell lines were used for the study. Low-dose-rate irradiation was used to determine the α component of the relationship between dose and micronucleus frequency according to the linear-quadratic (LQ) model. A reduction of the dose rate from 3.09 to 0.0142 Gy/min correspondingly decreased the micronucleus frequency; however, the fraction of binucleate cells without micronuclei was not affected in SCCVII and RIF-1 cells. When this fraction was defined as the normal nuclear division fraction, it decreased exponentially as a function of radiation dose. Then dose vs normal nuclear division fraction (NNDF) was fitted as follows: -In NNDF = aD + C, where D is radiation dose in grays and C is constant. The slope of the dose vs normal nuclear division fraction was not affected by dose rate. The correlation was also explored between the slope (a) and the α value of the cell survival curve determined by the colony formation assay in cells of eight cell lines. These two values showed extremely high agreement: α = 1.01a + 0.00795 (r = 0.99, P < 0.01). This assay was applied to estimate the α value of the cell survival curve of human esophageal cancer cell lines established from surgical specimens. 13 refs., 5 figs

  10. Phase II of a Six sigma Initiative to Study DWPF SME Analytical Turnaround Times: SRNL's Evaluation of Carbonate-Based Dissolution Methods

    International Nuclear Information System (INIS)

    The Analytical Development Section (ADS) and the Statistical Consulting Section (SCS) of the Savannah River National Laboratory (SRNL) are participating in a Six Sigma initiative to improve the Defense Waste Processing Facility (DWPF) Laboratory. The Six Sigma initiative has focused on reducing the analytical turnaround time of samples from the Slurry Mix Evaporator (SME) by developing streamlined sampling and analytical methods [1]. The objective of Phase I was to evaluate the sub-sampling of a larger sample bottle and the performance of a cesium carbonate (Cs2CO3) digestion method. Successful implementation of the Cs2CO3 fusion method in the DWPF would have important time savings and convenience benefits because this single digestion would replace the dual digestion scheme now used. A single digestion scheme would result in more efficient operations in both the DWPF shielded cells and the inductively coupled plasma--atomic emission spectroscopy (ICP-AES) laboratory. By taking a small aliquot of SME slurry from a large sample bottle and dissolving the vitrified SME sample with carbonate fusion methods, an analytical turnaround time reduction from 27 hours to 9 hours could be realized in the DWPF. This analytical scheme has the potential for not only dramatically reducing turnaround times, but also streamlining operations to minimize wear and tear on critical shielded cell components that are prone to fail, including the Hydragard(trademark) sampling valves and manipulators. Favorable results from the Phase I tests [2] led to the recommendation for a Phase II effort as outlined in the DWPF Technical Task Request (TTR) [3]. There were three major tasks outlined in the TTR, and SRNL issued a Task Technical and QA Plan [4] with a corresponding set of three major task activities: (1) Compare weight percent (wt%) total solids measurements of large volume samples versus peanut vial samples. (2) Evaluate Cs2CO3 and K2CO3 fusion methods using DWPF simulated glass (part 1

  11. Phase II of a Six sigma Initiative to Study DWPF SME Analytical Turnaround Times: SRNL's Evaluation of Carbonate-Based Dissolution Methods

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, Thomas

    2005-09-01

    The Analytical Development Section (ADS) and the Statistical Consulting Section (SCS) of the Savannah River National Laboratory (SRNL) are participating in a Six Sigma initiative to improve the Defense Waste Processing Facility (DWPF) Laboratory. The Six Sigma initiative has focused on reducing the analytical turnaround time of samples from the Slurry Mix Evaporator (SME) by developing streamlined sampling and analytical methods [1]. The objective of Phase I was to evaluate the sub-sampling of a larger sample bottle and the performance of a cesium carbonate (Cs{sub 2}CO{sub 3}) digestion method. Successful implementation of the Cs{sub 2}CO{sub 3} fusion method in the DWPF would have important time savings and convenience benefits because this single digestion would replace the dual digestion scheme now used. A single digestion scheme would result in more efficient operations in both the DWPF shielded cells and the inductively coupled plasma--atomic emission spectroscopy (ICP-AES) laboratory. By taking a small aliquot of SME slurry from a large sample bottle and dissolving the vitrified SME sample with carbonate fusion methods, an analytical turnaround time reduction from 27 hours to 9 hours could be realized in the DWPF. This analytical scheme has the potential for not only dramatically reducing turnaround times, but also streamlining operations to minimize wear and tear on critical shielded cell components that are prone to fail, including the Hydragard{trademark} sampling valves and manipulators. Favorable results from the Phase I tests [2] led to the recommendation for a Phase II effort as outlined in the DWPF Technical Task Request (TTR) [3]. There were three major tasks outlined in the TTR, and SRNL issued a Task Technical and QA Plan [4] with a corresponding set of three major task activities: (1) Compare weight percent (wt%) total solids measurements of large volume samples versus peanut vial samples. (2) Evaluate Cs{sub 2}CO{sub 3} and K{sub 2}CO{sub 3

  12. A mental health first aid training program for Australian Aboriginal and Torres Strait Islander peoples: description and initial evaluation

    Directory of Open Access Journals (Sweden)

    Hart Laura M

    2009-06-01

    Full Text Available Abstract Background Mental Health First Aid (MHFA training was developed in Australia to teach members of the public how to give initial help to someone developing a mental health problem or in a mental health crisis situation. However, this type of training requires adaptation for specific cultural groups in the community. This paper describes the adaptation of the program to create an Australian Aboriginal and Torres Strait Islander Mental Health First Aid (AMHFA course and presents an initial evaluation of its uptake and acceptability. Methods To evaluate the program, two types of data were collected: (1 quantitative data on uptake of the course (number of Instructors trained and courses subsequently run by these Instructors; (2 qualitative data on strengths, weaknesses and recommendations for the future derived from interviews with program staff and focus groups with Instructors and community participants. Results 199 Aboriginal people were trained as Instructors in a five day Instructor Training Course. With sufficient time following training, the majority of these Instructors subsequently ran 14-hour AMHFA courses for Aboriginal people in their community. Instructors were more likely to run courses if they had prior teaching experience and if there was post-course contact with one of the Trainers of Instructors. Analysis of qualitative data indicated that the Instructor Training Course and the AMHFA course are culturally appropriate, empowering for Aboriginal people, and provided information that was seen as highly relevant and important in assisting Aboriginal people with a mental illness. There were a number of recommendations for improvements. Conclusion The AMHFA program is culturally appropriate and acceptable to Aboriginal people. Further work is needed to refine the course and to evaluate its impact on help provided to Aboriginal people with mental health problems.

  13. A mental health first aid training program for Australian Aboriginal and Torres Strait Islander peoples: description and initial evaluation

    Science.gov (United States)

    Kanowski, Len G; Jorm, Anthony F; Hart, Laura M

    2009-01-01

    Background Mental Health First Aid (MHFA) training was developed in Australia to teach members of the public how to give initial help to someone developing a mental health problem or in a mental health crisis situation. However, this type of training requires adaptation for specific cultural groups in the community. This paper describes the adaptation of the program to create an Australian Aboriginal and Torres Strait Islander Mental Health First Aid (AMHFA) course and presents an initial evaluation of its uptake and acceptability. Methods To evaluate the program, two types of data were collected: (1) quantitative data on uptake of the course (number of Instructors trained and courses subsequently run by these Instructors); (2) qualitative data on strengths, weaknesses and recommendations for the future derived from interviews with program staff and focus groups with Instructors and community participants. Results 199 Aboriginal people were trained as Instructors in a five day Instructor Training Course. With sufficient time following training, the majority of these Instructors subsequently ran 14-hour AMHFA courses for Aboriginal people in their community. Instructors were more likely to run courses if they had prior teaching experience and if there was post-course contact with one of the Trainers of Instructors. Analysis of qualitative data indicated that the Instructor Training Course and the AMHFA course are culturally appropriate, empowering for Aboriginal people, and provided information that was seen as highly relevant and important in assisting Aboriginal people with a mental illness. There were a number of recommendations for improvements. Conclusion The AMHFA program is culturally appropriate and acceptable to Aboriginal people. Further work is needed to refine the course and to evaluate its impact on help provided to Aboriginal people with mental health problems. PMID:19490648

  14. Overcoming challenges to initiating cell therapy clinical trials in rapidly developing countries: India as a model.

    Science.gov (United States)

    Viswanathan, Sowmya; Rao, Mahendra; Keating, Armand; Srivastava, Alok

    2013-08-01

    Increasingly, a number of rapidly developing countries, including India, China, Brazil, and others, are becoming global hot spots for the development of regenerative medicine applications, including stem cell-based therapies. Identifying and overcoming regulatory and translational research challenges and promoting scientific and ethical clinical trials with cells will help curb the growth of stem cell tourism for unproven therapies. It will also enable academic investigators, local regulators, and national and international biotechnology and biopharmaceutical companies to accelerate stem cell-based clinical research that could lead to effective innovative treatments in these regions. Using India as a model system and obtaining input from regulators, clinicians, academics, and industry representatives across the stem cell field in India, we reviewed the role of key agencies and processes involved in this field. We have identified areas that need attention and here provide solutions from other established and functioning models in the world to streamline and unify the regulatory and ethics approval processes for cell-based therapies. We also make recommendations to check the growth and functioning of clinics offering unproven treatments. Addressing these issues will remove considerable hurdles to both local and international investigators, accelerate the pace of research and development, and create a quality environment for reliable products to emerge. By doing so, these countries would have taken one important step to move to the forefront of stem cell-based therapeutics. PMID:23836804

  15. NF-κB Functions in Tumor Initiation by Suppressing the Surveillance of Both Innate and Adaptive Immune Cells

    Directory of Open Access Journals (Sweden)

    David J. Wang

    2014-10-01

    Full Text Available NF-κB is considered a major contributor to tumor development, but how this factor functions in the initial stages of oncogenesis is not clear. In a model of Ras-induced transformation, we probed NF-κB function as preneoplastic cells formed tumors in mice. As previously shown, the p65 subunit of NF-κB acts as a tumor suppressor in normal cells by sustaining senescence following DNA damage. Our current data reveal that, following immortalization, p65 switches to an oncogene by counteracting the surveillance properties of immune cells. NF-κB exerts this effect by protecting transformed cells against macrophage-derived proapoptotic factors, tumor necrosis factor, and nitric oxide. Additionally, NF-κB acts through transforming growth factor beta (TGF-β to mitigate T cell cytotoxicity and other factors to expand myeloid-derived suppressor cells. Together, these data suggest that NF-κB functions in the early stages of transformation by suppressing immune surveillance of both innate and adaptive immune cells, information that may be useful for targeted immunotherapies.

  16. Externalization and recognition by macrophages of large subunit of eukaryotic translation initiation factor 3 in apoptotic cells

    International Nuclear Information System (INIS)

    We previously isolated a monoclonal antibody named PH2 that inhibits phosphatidylserine-mediated phagocytosis of apoptotic cells by macrophages [C. Fujii, A. Shiratsuchi, J. Manaka, S. Yonehara, Y. Nakanishi. Cell Death Differ. 8 (2001) 1113-1122]. We report here the identification of the cognate antigen. A protein bound by PH2 in Western blotting was identified as the 170-kDa subunit of eukaryotic translation initiation factor 3 (eIF3 p170/eIF3a). When eIF3a was expressed in a culture cell line as a protein fused to green fluorescence protein, the fusion protein was detected at the cell surface only after the induction of apoptosis. The same phenomenon was seen when the localization of endogenous eIF3a was determined using anti-eIF3a antibody, and eIF3a seemed to be partially degraded during apoptosis. Furthermore, bacterially expressed N-terminal half of eIF3a fused to glutathione S-transferase bound to the surface of macrophages and inhibited phagocytosis of apoptotic cells by macrophages when it was added to phagocytosis reactions. These results collectively suggest that eIF3a translocates to the cell surface upon apoptosis, probably after partial degradation, and bridges apoptotic cells and macrophages to enhance phagocytosis

  17. Evaluation of the Redesign of an Undergraduate Cell Biology Course

    OpenAIRE

    McEwen, Laura April; Harris, dik; Schmid, Richard F.; Vogel, Jackie; Western, Tamara; Harrison, Paul

    2009-01-01

    This article offers a case study of the evaluation of a redesigned and redeveloped laboratory-based cell biology course. The course was a compulsory element of the biology program, but the laboratory had become outdated and was inadequately equipped. With the support of a faculty-based teaching improvement project, the teaching team redesigned the course and re-equipped the laboratory, using a more learner-centered, constructivist approach. The focus of the article is on the project-supported...

  18. Evaluation of nitroimidazole hypoxic cell radiosensitizers in a human tumor cell line high in intracellular glutathione

    International Nuclear Information System (INIS)

    Five nitroimidazole hypoxic cell radiosensitizers were evaluated in a human lung adenocarcinoma cell line (A549) whose GSH level was 8-fold higher than Chinese hamster V79 cells. One millimolar concentrations of Misonidazole (MISO), SR-2508, RSU-1164, RSU-1172, and Ro-03-8799 sensitized hypoxic A549 cells to radiation, with Ro-03-8799 giving the highest sensitizer enhancement ration (SER) (2.3). However, MISO, SR-2508 and Ro-03-8799 were less effective in this cell line than in V79 cells, presumably due to higher GSH content of the A549 cells. Increased hypoxic radiosensitization was seen with 0.1 mM Ro-03-8799 after GSH depletion by BSO as compared to 0.1 mM Ro-03-8799 alone (SER-1.8 vs 1.3). The combination of GSH depletion and 0.1 mM Ro-03-8799 was considerably more toxic than 0.1 mM or 1.0 mM Ro-03-8799 alone. This sensitivity was much greater than has been observed for SR-2508. These data show that Ro-03-8799 was the most efficient hypoxic cell radiosensitizer in a human tumor cell line considerably higher in GSH than the rodent cell lines often used in hypoxic radiosensitization studies. Thus, Ro-03-8799 may be a more effective hypoxic cell sensitizer in human tumors that are high in GSH

  19. Lithium Iron Phosphate Cell Performance Evaluations for Lunar Extravehicular Activities

    Science.gov (United States)

    Reid, Concha

    2007-01-01

    Lithium-ion battery cells are being evaluated for their ability to provide primary power and energy storage for NASA s future Exploration missions. These missions include the Orion Crew Exploration Vehicle, the Ares Crew Launch Vehicle Upper Stage, Extravehicular Activities (EVA, the advanced space suit), the Lunar Surface Ascent Module (LSAM), and the Lunar Precursor and Robotic Program (LPRP), among others. Each of these missions will have different battery requirements. Some missions may require high specific energy and high energy density, while others may require high specific power, wide operating temperature ranges, or a combination of several of these attributes. EVA is one type of mission that presents particular challenges for today s existing power sources. The Portable Life Support System (PLSS) for the advanced Lunar surface suit will be carried on an astronaut s back during eight hour long sorties, requiring a lightweight power source. Lunar sorties are also expected to occur during varying environmental conditions, requiring a power source that can operate over a wide range of temperatures. Concepts for Lunar EVAs include a primary power source for the PLSS that can recharge rapidly. A power source that can charge quickly could enable a lighter weight system that can be recharged while an astronaut is taking a short break. Preliminary results of Al23 Ml 26650 lithium iron phosphate cell performance evaluations for an advanced Lunar surface space suit application are discussed in this paper. These cells exhibit excellent recharge rate capability, however, their specific energy and energy density is lower than typical lithium-ion cell chemistries. The cells were evaluated for their ability to provide primary power in a lightweight battery system while operating at multiple temperatures.

  20. Evaluation capacity development in Africa: Current landscape of international partners’ initiatives, lessons learned and the way forward

    Directory of Open Access Journals (Sweden)

    Michele Tarsilla

    2014-12-01

    Full Text Available Despite the copious resources allocated by international development partners to enhance African countries’ capacity to evaluate the performance and impact of development programmes and policies, most evaluation capacity building (ECB efforts have not yielded the expected results. Time and energy have been focused on the measurement of short-term effects whilst long-term results have largely remained elusive. As a result, a variety of actors across the continent are calling for more innovative strategies. In particular, more efforts are currently being made to revitalise the evaluation function in international development at the global level and to enhance a shift from short-term training to more contextually relevant, systemic learning, equity and sustainability efforts. This article aims to provide a critical overview of ECB initiatives undertaken by international development partners in Africa over five years (2009–2014 that worked well and investigate how they could be improved. The common issues stress the need for harmonisation and collaboration between international partners and African institutions and more effective collaboration with in country institutions and organisations committed to evaluation capacity development (ECD. The analysis in this article is timely and relevant for both the strengthening of socalled made-in Africa evaluation methods and approaches and the roll-out of systemic and organic ECD strategies. The debate spurred by this article is likely to contribute to the current global debate on what strategies ought to be taken as part of the post-2015 agenda. This inturn will spur the debate on ECD to increase in importance and undoubtedly in intensity.

  1. Protein markers of cancer-associated fibroblasts and tumor-initiating cells reveal subpopulations in freshly isolated ovarian cancer ascites

    Directory of Open Access Journals (Sweden)

    Wintzell My

    2012-08-01

    Full Text Available Abstract Background In ovarian cancer, massive intraperitoneal dissemination is due to exfoliated tumor cells in ascites. Tumor-initiating cells (TICs or cancer stem cells and cells showing epithelial-mesenchymal-transition (EMT are particularly implicated. Spontaneous spherical cell aggregates are sometimes observed, but although similar to those formed by TICs in vitro, their significance is unclear. Methods Cells freshly isolated from malignant ascites were separated into sphere samples (S-type samples, n=9 and monolayer-forming single-cell suspensions (M-type, n=18. Using western blot, these were then compared for expression of protein markers of EMT, TIC, and of cancer-associated fibroblasts (CAFs. Results S-type cells differed significantly from M-type by expressing high levels of E-cadherin and no or little vimentin, integrin-β3 or stem cell transcription factor Oct-4A. By contrast, M-type samples were enriched for CD44, Oct-4A and for CAF markers. Independently of M- and S-type, there was a strong correlation between TIC markers Nanog and EpCAM. The CAF marker α-SMA correlated with clinical stage IV. This is the first report on CAF markers in malignant ascites and on SUMOylation of Oct-4A in ovarian cancer. Conclusions In addition to demonstrating potentially high levels of TICs in ascites, the results suggest that the S-type population is the less tumorigenic one. Nanoghigh/EpCAMhigh samples represent a TIC subset which may be either M- or S-type, and which is separate from the CD44high/Oct-4Ahigh subset observed only in M-type samples. This demonstrates a heterogeneity in TIC populations in vivo which has practical implications for TIC isolation based on cell sorting. The biological heterogeneity will need to be addressed in future therapeutical strategies.

  2. Protein markers of cancer-associated fibroblasts and tumor-initiating cells reveal subpopulations in freshly isolated ovarian cancer ascites

    International Nuclear Information System (INIS)

    In ovarian cancer, massive intraperitoneal dissemination is due to exfoliated tumor cells in ascites. Tumor-initiating cells (TICs or cancer stem cells) and cells showing epithelial-mesenchymal-transition (EMT) are particularly implicated. Spontaneous spherical cell aggregates are sometimes observed, but although similar to those formed by TICs in vitro, their significance is unclear. Cells freshly isolated from malignant ascites were separated into sphere samples (S-type samples, n=9) and monolayer-forming single-cell suspensions (M-type, n=18). Using western blot, these were then compared for expression of protein markers of EMT, TIC, and of cancer-associated fibroblasts (CAFs). S-type cells differed significantly from M-type by expressing high levels of E-cadherin and no or little vimentin, integrin-β3 or stem cell transcription factor Oct-4A. By contrast, M-type samples were enriched for CD44, Oct-4A and for CAF markers. Independently of M- and S-type, there was a strong correlation between TIC markers Nanog and EpCAM. The CAF marker α-SMA correlated with clinical stage IV. This is the first report on CAF markers in malignant ascites and on SUMOylation of Oct-4A in ovarian cancer. In addition to demonstrating potentially high levels of TICs in ascites, the results suggest that the S-type population is the less tumorigenic one. Nanoghigh/EpCAMhigh samples represent a TIC subset which may be either M- or S-type, and which is separate from the CD44high/Oct-4Ahigh subset observed only in M-type samples. This demonstrates a heterogeneity in TIC populations in vivo which has practical implications for TIC isolation based on cell sorting. The biological heterogeneity will need to be addressed in future therapeutical strategies

  3. Test and Approval Center for Fuel Cell and Hydrogen Technologies: Phase I. Initiation

    DEFF Research Database (Denmark)

    mitigation of the human-caused global warming. Fuel cells (in particular solid oxide fuel cells) produce electricity and heat at higher efficiencies than conventional power plants. They emit less pollutants - for example no toxic NOx at all - than conventional plants do. Fuel cells can operate on fossil...... fuels (natural gas) and on alternative fuels as well. They can therefore bridge the gap between availability and efficient use of fossil fuels on the short term and establishment of an energy market based on renewables on the long term. Hydrogen is a zero carbon energy carrier that– just like......Fuel cells and hydrogen technologies hold the potential for decreasing emissions of greenhouse gases and air pollutants, for facilitating the increased use of renewable energy sources with high efficiencies and thereby contributing to the establishment of a sustainable energy system and the...

  4. Evaluation of ISABELLE full cell ultra high vacuum system

    International Nuclear Information System (INIS)

    The ISABELLE Full Cell Vacuum System consisting of a 40 m long, by 8.8 cm diameter stainless steel tube pumped by seven pumping stations was assembled and processed for 10-12 Torr operation. Evaluation and testing of the system and its sub-assemblies has been completed. Detail design of system components and the determination of the conditioning process was completed. The best procedure to rough pump, leak test, vacuum bake the system, condition pumps, degas gauges, turn on ion pumps and flash sublimation pumps was established. Pressures below 2 x 10-11 Torr are now routinely achieved in normal operation of the Full Cell. This includes pump down after replacement of various components and pump down after back fill with moist unfiltered air. The techniques developed for the Full Cell will be used to build the ISABELLE Ultra High Vacuum System

  5. Evaluating Cell Processes, Quality, and Biomarkers in Pluripotent Stem Cells Using Video Bioinformatics.

    Science.gov (United States)

    Zahedi, Atena; On, Vincent; Lin, Sabrina C; Bays, Brett C; Omaiye, Esther; Bhanu, Bir; Talbot, Prue

    2016-01-01

    There is a foundational need for quality control tools in stem cell laboratories engaged in basic research, regenerative therapies, and toxicological studies. These tools require automated methods for evaluating cell processes and quality during in vitro passaging, expansion, maintenance, and differentiation. In this paper, an unbiased, automated high-content profiling toolkit, StemCellQC, is presented that non-invasively extracts information on cell quality and cellular processes from time-lapse phase-contrast videos. Twenty four (24) morphological and dynamic features were analyzed in healthy, unhealthy, and dying human embryonic stem cell (hESC) colonies to identify those features that were affected in each group. Multiple features differed in the healthy versus unhealthy/dying groups, and these features were linked to growth, motility, and death. Biomarkers were discovered that predicted cell processes before they were detectable by manual observation. StemCellQC distinguished healthy and unhealthy/dying hESC colonies with 96% accuracy by non-invasively measuring and tracking dynamic and morphological features over 48 hours. Changes in cellular processes can be monitored by StemCellQC and predictions can be made about the quality of pluripotent stem cell colonies. This toolkit reduced the time and resources required to track multiple pluripotent stem cell colonies and eliminated handling errors and false classifications due to human bias. StemCellQC provided both user-specified and classifier-determined analysis in cases where the affected features are not intuitive or anticipated. Video analysis algorithms allowed assessment of biological phenomena using automatic detection analysis, which can aid facilities where maintaining stem cell quality and/or monitoring changes in cellular processes are essential. In the future StemCellQC can be expanded to include other features, cell types, treatments, and differentiating cells. PMID:26848582

  6. Evaluating Cell Processes, Quality, and Biomarkers in Pluripotent Stem Cells Using Video Bioinformatics.

    Directory of Open Access Journals (Sweden)

    Atena Zahedi

    Full Text Available There is a foundational need for quality control tools in stem cell laboratories engaged in basic research, regenerative therapies, and toxicological studies. These tools require automated methods for evaluating cell processes and quality during in vitro passaging, expansion, maintenance, and differentiation. In this paper, an unbiased, automated high-content profiling toolkit, StemCellQC, is presented that non-invasively extracts information on cell quality and cellular processes from time-lapse phase-contrast videos. Twenty four (24 morphological and dynamic features were analyzed in healthy, unhealthy, and dying human embryonic stem cell (hESC colonies to identify those features that were affected in each group. Multiple features differed in the healthy versus unhealthy/dying groups, and these features were linked to growth, motility, and death. Biomarkers were discovered that predicted cell processes before they were detectable by manual observation. StemCellQC distinguished healthy and unhealthy/dying hESC colonies with 96% accuracy by non-invasively measuring and tracking dynamic and morphological features over 48 hours. Changes in cellular processes can be monitored by StemCellQC and predictions can be made about the quality of pluripotent stem cell colonies. This toolkit reduced the time and resources required to track multiple pluripotent stem cell colonies and eliminated handling errors and false classifications due to human bias. StemCellQC provided both user-specified and classifier-determined analysis in cases where the affected features are not intuitive or anticipated. Video analysis algorithms allowed assessment of biological phenomena using automatic detection analysis, which can aid facilities where maintaining stem cell quality and/or monitoring changes in cellular processes are essential. In the future StemCellQC can be expanded to include other features, cell types, treatments, and differentiating cells.

  7. Matrix Metalloproteinase-10 Is Required for Lung Cancer Stem Cell Maintenance, Tumor Initiation and Metastatic Potential

    OpenAIRE

    Verline Justilien; Regala, Roderick P.; I-Chu Tseng; Walsh, Michael P.; Jyotica Batra; Radisky, Evette S.; Murray, Nicole R.; Fields, Alan P.

    2012-01-01

    Matrix metalloproteinases (Mmps) stimulate tumor invasion and metastasis by degrading the extracellular matrix. Here we reveal an unexpected role for Mmp10 (stromelysin 2) in the maintenance and tumorigenicity of mouse lung cancer stem-like cells (CSC). Mmp10 is highly expressed in oncosphere cultures enriched in CSCs and RNAi-mediated knockdown of Mmp10 leads to a loss of stem cell marker gene expression and inhibition of oncosphere growth, clonal expansion, and transformed growth in vitro. ...

  8. Role of multidisciplinary approach in a case of Langerhans cell histiocytosis with initial periodontal manifestations

    OpenAIRE

    A. Cisternino; F. Asa'Ad; FUSCO, N.; Ferrero, S; Rasperini, G

    2015-01-01

    Introduction: Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasia of unknown etiology occurring in both children and adults. This condition is characterized by an abnormal proliferation of Langerhans cells that may virtually affect all sites in the human body. Oral manifestations of LCH could be the first clinical sign of disease and its periodontal localization could be easily mistaken for other more common entities, such as chronic periodontitis, aggressive periodon...

  9. Innate lymphoid cells in the initiation, regulation and resolution of inflammation

    OpenAIRE

    Sonnenberg, Gregory F.; Artis, David

    2015-01-01

    A previously unappreciated cell type of the innate immune system, termed innate lymphoid cells (ILCs), has been characterized in mice and humans, and found to profoundly influence the induction, regulation and resolution of inflammation. ILCs play an important role in these processes in murine models of infection, inflammatory disease and tissue repair. Further, disease association studies in defined patient populations have identified significant alterations in ILC responses, suggesting a po...

  10. Initial evaluation of dry storage issues for spent nuclear fuels in wet storage at the Idaho Chemical Processing Plant

    Energy Technology Data Exchange (ETDEWEB)

    Guenther, R J; Johnson, Jr, A B; Lund, A L; Gilbert, E R [and others

    1996-07-01

    The Pacific Northwest Laboratory has evaluated the basis for moving selected spent nuclear fuels in the CPP-603 and CPP-666 storage pools at the Idaho Chemical Processing Plant from wet to dry interim storage. This work is being conducted for the Lockheed Idaho Technologies Company as part of the effort to determine appropriate conditioning and dry storage requirements for these fuels. These spent fuels are from 22 test reactors and include elements clad with aluminum or stainless steel and a wide variety of fuel materials: UAl{sub x}, UAl{sub x}-Al and U{sub 3}O{sub 8}-Al cermets, U-5% fissium, UMo, UZrH{sub x}, UErZrH, UO{sub 2}-stainless steel cermet, and U{sub 3}O{sub 8}-stainless steel cermet. The study also included declad uranium-zirconium hydride spent fuel stored in the CPP-603 storage pools. The current condition and potential failure mechanisms for these spent fuels were evaluated to determine the impact on conditioning and dry storage requirements. Initial recommendations for conditioning and dry storage requirements are made based on the potential degradation mechanisms and their impacts on moving the spent fuel from wet to dry storage. Areas needing further evaluation are identified.

  11. The role of PET in initial work-up and evaluation after therapy in patients with carcinoma of unknown primary

    Energy Technology Data Exchange (ETDEWEB)

    Ryoo, Baek Yeol; Kang, Yoon Koo

    1998-12-01

    The carcinoma of unknown primary occupied 5 - 10 % of all malignancies. It is heterogenous in origin and has poor prognosis. The indentification of primary site and definition of involved area are more helpful in the management. The efficacy of positron emission tomography (PET) with fluorine-18- fluorodeoxyglucose (F18-FDG) positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (F18-FDG) was evaluated in several tumors such as breast, pancreas and head and neck cancers. In carcinoma of unknown primary, it was reported that the concentration of FDG was increased in tumor tissues, and that PET with F18-FDG may be much helpful in identifying primary site and defining involved area. The authors evaluated the usefulness of PET with F18-FDG in initial work-up and in evaluation after radical therapy for the patients with carcinoma of unknown primary. The visual analysis of FDG-PET would be helpful in identifying primary site and defining involved area. In detecting recurrent of residual lesions, FDG-PET seemed to be less helpful than conventional diagnostic work-up. But more studies with larger number of cases and longer follow-up were required. The results of this study can be bases for the direction of future studies for the usefulness of PET in carcinoma of unknown primary.

  12. Initial evaluation of dry storage issues for spent nuclear fuels in wet storage at the Idaho Chemical Processing Plant

    International Nuclear Information System (INIS)

    The Pacific Northwest Laboratory has evaluated the basis for moving selected spent nuclear fuels in the CPP-603 and CPP-666 storage pools at the Idaho Chemical Processing Plant from wet to dry interim storage. This work is being conducted for the Lockheed Idaho Technologies Company as part of the effort to determine appropriate conditioning and dry storage requirements for these fuels. These spent fuels are from 22 test reactors and include elements clad with aluminum or stainless steel and a wide variety of fuel materials: UAlx, UAlx-Al and U3O8-Al cermets, U-5% fissium, UMo, UZrHx, UErZrH, UO2-stainless steel cermet, and U3O8-stainless steel cermet. The study also included declad uranium-zirconium hydride spent fuel stored in the CPP-603 storage pools. The current condition and potential failure mechanisms for these spent fuels were evaluated to determine the impact on conditioning and dry storage requirements. Initial recommendations for conditioning and dry storage requirements are made based on the potential degradation mechanisms and their impacts on moving the spent fuel from wet to dry storage. Areas needing further evaluation are identified

  13. Human granulosa-luteal cells initiate an innate immune response to pathogen-associated molecules.

    Science.gov (United States)

    Ibrahim, Laila A; Kramer, Joseph M; Williams, R Stan; Bromfield, John J

    2016-10-01

    The microenvironment of the ovarian follicle is key to the developmental success of the oocyte. Minor changes within the follicular microenvironment can significantly disrupt oocyte development, compromising the formation of competent embryos and reducing fertility. Previously described as a sterile environment, the ovarian follicle of women has been shown to contain colonizing bacterial strains, whereas in domestic species, pathogen-associated molecules are concentrated in the follicular fluid of animals with uterine infection. The aim of this study is to determine whether human granulosa-luteal cells mount an innate immune response to pathogen-associated molecules, potentially disrupting the microenvironment of the ovarian follicle. Human granulosa-luteal cells were collected from patients undergoing assisted reproduction. Cells were cultured in the presence of pathogen-associated molecules (LPS, FSL-1 and Pam3CSK4) for 24h. Supernatants and total RNA were collected for assessment by PCR and ELISA. Granulosa-luteal cells were shown to express the molecular machinery required to respond to a range of pathogen-associated molecules. Expression of TLR4 varied up to 15-fold between individual patients. Granulosa-luteal cells increased the expression of the inflammatory mediators IL1B, IL6 and CXCL8 in the presence of the TLR4 agonist E. coli LPS. Similarly, the TLR2/6 ligand, FSL-1, increased the expression of IL6 and CXCL8. Although no detectable changes in CYP19A1 or STAR expression were observed in granulosa-luteal cells following challenge, a significant reduction in progesterone secretion was measured after treatment with FSL-1. These findings demonstrate the ability of human granulosa-luteal cells to respond to pathogen-associated molecules and generate an innate immune response. PMID:27512120

  14. Evaluating the performance of microbial fuel cells powering electronic devices

    Energy Technology Data Exchange (ETDEWEB)

    Dewan, Alim; Beyenal, Haluk [Gene and Linda Voiland School of Chemical Engineering and Bioengineering, Center for Environmental, Sediment and Aquatic Research, Pullman, WA (United States); Donovan, Conrad; Heo, Deukhyoun [School of Electrical Engineering and Computer Science, Washington State University, Pullman, WA 99163-2710 (United States)

    2010-01-01

    A microbial fuel cell (MFC) is capable of powering an electronic device if we store the energy in an external storage device, such as a capacitor, and dispense that energy intermittently in bursts of high-power when needed. Therefore its performance needs to be evaluated using an energy-storing device such as a capacitor which can be charged and discharged rather than other evaluation techniques, such as continuous energy dissipation through a resistor. In this study, we develop a method of testing microbial fuel cell performance based on storing energy in a capacitor. When a capacitor is connected to a MFC it acts like a variable resistor and stores energy from the MFC at a variable rate. In practice the application of this method to testing microbial fuel cells is very challenging and time consuming; therefore we have custom-designed a microbial fuel cell tester (MFCT). The MFCT evaluates the performance of a MFC as a power source. It uses a capacitor as an energy storing device and waits until a desired amount of energy is stored then discharges the capacitor. The entire process is controlled using an analog-to-digital converter (ADC) board controlled by a custom-written computer program. The utility of our method and the MFCT is demonstrated using a laboratory microbial fuel cell (LMFC) and a sediment microbial fuel cell (SMFC). We determine (1) how frequently a MFC can charge a capacitor, (2) which electrode is current-limiting, (3) what capacitor value will allow the maximum harvested energy from a MFC, which is called the ''optimum charging capacitor value,'' and (4) what capacitor charging potential will harvest the maximum energy from a MFC, which is called the ''optimum charging potential.'' Using a LMFC we find that (1) the time needed to charge a 3-F capacitor from 0 to 500 mV is 108 min, (2) the optimum charging capacitor value is 3 F, and (3) the optimum charging potential is 300 mV. Using a SMFC we find that (1

  15. Initial evaluation of vertigo

    Directory of Open Access Journals (Sweden)

    Lemajić-Komazec Slobodanka

    2006-01-01

    Full Text Available Dizziness is one of the most common reasons patients visit their physicians. Balance control depends on receiving afferent sensory information from several sensory systems: vestibular, optical and proprioceptive. Bioelectric signals, generated by body movements in the semicircular canals and in the otolithic apparatus, are transported via the vestibular nerve to the vestibular nucleus. All four vestibular nuclei, located bilaterally in medial longitudinal fasciculus, are linked with central nervous system structures. These central nervous system structures are involved in maintaining visual stability, spatial orientation and balance control. Nystagmus is a result of afferent signals balance disorders. Nystagmus due to peripheral lesions is conjugate nystagmus, because there is a bilateral central connection. Lesions above the vestibular nuclei induce deficits in synchronization and conjugation of eye movements, thus the nystagmus is dissociated. This paper shows that in peripheral vestibular disorders spontaneous nystagmus is rhythmic, associated, horizontal-rotatory or horizontal, with subjective sensation of dizziness which decreases with time and harmonic signs whose direction coincides with the slow phase of nystagmus and it is associated with mild disorders during pendular stimulation with statistically significant vestibular hypofunction. Spontaneous nystagmus in central vestibular lesions is severe, dissociated, horizontal, rotatory or vertical, without changes related to optical suppression; if vestibular symptoms are present, they are non-harmonic. In central disorders, findings after thermal stimulation are either normal or pathological, with dysrhythmias and inhibition in pendular stimulation. This paper deals with differential diagnosis of vertigo based on anamnesis and clinical examination, as well as objective diagnostic tests. .

  16. A Cell Lysis and Protein Purification - Single Molecule Assay Devices for Evaluation of Genetically Engineered Proteins

    Science.gov (United States)

    Nakyama, Tetsuya; Tabata, Kazuhito; Noji, Hiroyuki; Yokokawa, Ryuji

    We have developed two devices applicable to evaluate genetically engineered proteins in single molecule assay: on-chip cell lysis device, and protein purification - assay device. A motor protein, F1-ATPase expressed in E.coli, was focused in this report as a target protein. Cell lysis was simply performed by applying pulse voltage between Au electrodes patterned by photolithography, and its efficiency was determined by absorptiometry. The subsequent processes, purification and assay of extracted proteins, were demonstrated in order to detect F1-ATPase and to evaluate its activity. The specific bonding between his-tag in F1-ATPase and Ni-NTA coated on a glass surface was utilized for the purification process. After immobilization of F1-ATPase, avidin-coated microspheres and adenosine tri-phosphate (ATP) solution were infused sequentially to assay the protein. Microsphere rotation was realized by activity of F1-ATPase corresponding to ATP hydrolysis. Results show that the cell lysis device, at the optimum condition, extracts enough amount of protein for single molecule assay. Once cell lysate was injected to the purification - assay device, proteins were diffused in the lateral direction in a Y-shape microchannel. The gradient of protein concentratioin provides an optimal concentration for the assay i.e. the highest density of rotating beads. Density of rotating beads is also affected by the initial concentration of protein injected to the device. The optimum concentration was achieved by our cell lysis device not by the conventional method by ultrasonic wave. Rotation speed was analyzed for several microspheres assayed in the purification - assay device, and the results were compatible to that of conventional assay in which F1-ATPase was purified in bulk scale. In conclusion, we have demonstrated on-chip cell lysis and assay appropriate for the sequential analysis without any pretreatment. On-chip devices replacing conventional bioanalytical methods will be

  17. Control of mammalian cell mutagenesis and differentiation by chemicals which initiate or promote tumor formation

    Energy Technology Data Exchange (ETDEWEB)

    Jones, C. A.; Huberman, E.

    1980-01-01

    A cell-mediated mutagenesis assay was developed to predict the potential carcinogenic hazard of some environmental chemicals. In this assay, Chinese hamster V79 cells, which are susceptible to mutagenesis, are co-cultivated with cells capable of metabolizing chemical carcinogens. Use of this assay made it possible to demonstrate a relationship between the degree of carcinogenicity and mutagenicity of a series of polycyclic hydrocarbons and nitrosamines and to study the organ specificity exhibited by some chemical carcinogens. However, most short-term in vitro assays are designed to detect mutagenic activity and therefore do not detect tumor promoting agents which are devoid of this activity. By analyzing various markers of terminal differentiation in cultured human melanoma and myeloid leukemia cells, we have established a relationship between the activity of a series of tumor promoting phorbol diesters in the mouse skin and their ability to induce terminal differentiation. We suggest that measuring alterations in the differentiation characteristics of some cultured cells may represent an approach by which environmental tumor promoting agents can be studied and detected.

  18. [Theodor Huzella and the initiation of research on the interactions between cells and the extracellular matrix].

    Science.gov (United States)

    Robert, Ladislas; Labat-Robert, Jacqueline; Michel Robert, Alexandre

    2012-01-01

    Interactions between cells and the surrounding "biomatrix", mediated by receptors as integrins or the elastin receptor is the most important topic in up to date research on connective tissues. Looking for the origin of this concept, one finds the pioneering work of Theodor Huzella, professor of histology-embryology at the Medical University of Budapest during pre-world war II decades. Using time-laps micro-cinematography in reflected light, he visualized the important role of connective tissue fibers, prepared in his laboratory, for the oriented migration of normal and malignant cells. His theoretical explanations, attributing an "active" role to the elasticity of the argyrophilic fibrous network in the coordination of cell societies, can now be reinterpreted in the light of recent work on the mechanotransduction of "messages" from the extracellular matrix to the cell inside. We propose a succinct review of Huzella's work and theories reinterpreted in the light of up-to-date knowledge on cell-matrix interactions. PMID:22748046

  19. Keeping health staff healthy: evaluation of a workplace initiative to reduce morbidity and mortality from HIV/AIDS in Malawi

    Directory of Open Access Journals (Sweden)

    Bemelmans Marielle

    2011-01-01

    Full Text Available Abstract Background In Malawi, the dramatic shortage of human resources for health is negatively impacted by HIV-related morbidity and mortality among health workers and their relatives. Many staff find it difficult to access HIV care through regular channels due to fear of stigma and discrimination. In 2006, two workplace initiatives were implemented in Thyolo District: a clinic at the district hospital dedicated to all district health staff and their first-degree relatives, providing medical services, including HIV care; and a support group for HIV-positive staff. Methods Using routine programme data, we evaluated the following outcomes up to the end of 2009: uptake and outcome of HIV testing and counselling among health staff and their dependents; uptake and outcomes of antiretroviral therapy (ART among health staff; and membership and activities of the support group. In addition, we included information from staff interviews and a job satisfaction survey to describe health workers' opinions of the initiatives. Results Almost two-thirds (91 of 144, 63% of health workers and their dependents undergoing HIV testing and counselling at the staff clinic tested HIV positive. Sixty-four health workers had accessed ART through the staff clinic, approximately the number of health workers estimated to be in need of ART. Of these, 60 had joined the support group. Cumulative ART outcomes were satisfactory, with more than 90% alive on treatment as of June 2009 (the end of the study observation period. The availability, confidentiality and quality of care in the staff clinic were considered adequate by beneficiaries. Conclusions Staff clinic and support group services successfully provided care and support to HIV-positive health workers. Similar initiatives should be considered in other settings with a high HIV prevalence.

  20. The role of maintenance proteins in the preservation of epithelial cell identity during mammary gland remodeling and breast cancer initiation

    Directory of Open Access Journals (Sweden)

    Danila Coradini

    2014-02-01

    Full Text Available During normal postnatal mammary gland development and adult remodeling related to the menstrual cycle, pregnancy, and lactation, ovarian hormones and peptide growth factors contribute to the delineation of a definite epithelial cell identity. This identity is maintained during cell replication in a heritable but DNA-independent manner. The preservation of cell identity is fundamental, especially when cells must undergo changes in response to intrinsic and extrinsic signals. The maintenance proteins, which are required for cell identity preservation, act epigenetically by regulating gene expression through DNA methylation, histone modification, and chromatin remodeling. Among the maintenance proteins, the Trithorax (TrxG and Polycomb (PcG group proteins are the best characterized. In this review, we summarize the structures and activities of the TrxG and PcG complexes and describe their pivotal roles in nuclear estrogen receptor activity. In addition, we provide evidence that perturbations in these epigenetic regulators are involved in disrupting epithelial cell identity, mammary gland remodeling, and breast cancer initiation.