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

    for Evaluating Actions of a Structural Nature”, that in 1999 presented the main guidelines, standards and recommendations of the European Commission for the assessment of socio-economic development programs involving Community funding. Several were the changes proposed by this guide, among others, a 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......The relevance of the relationship between evaluation and learning is widely acknowledged; as well as the importance of this learning process to support policy decision making and to judge the value of “what was done”, “how” and “with what results”. Although the activity of evaluation...

  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. 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

  5. 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.

  6. Design, Synthesis, and Initial Biological Evaluation of a Steroidal Anti-estrogen–Doxorubicin Bioconjugate for Targeting Estrogen Receptor-Positive Breast Cancer Cells

    Science.gov (United States)

    Dao, Kinh-Luan; Sawant, Rupa R.; Ronga, Victoria; Torchilin, Vladimir P.; Hanson, Robert N.

    2012-01-01

    As part of our program to develop breast cancer specific therapeutic agents we have synthesized a conjugate-agent that is a conjugate of the steroidal anti-estrogen and the potent cytotoxin doxorubicin. In this effort we employed a modular assembly approach to prepare a novel 11β-substituted steroidal anti-estrogen functionalized with an azido-tetraethylene glycol moiety which could be coupled to a complementary doxorubicin benzoyl hydrazone functionalized with a propargyl tetraethylene glycol moiety. Huisgen [3+2] cycloaddition chemistry gave the final hybrid that was evaluated for selective uptake and cytotoxicity in ER(+)-MCF-7 and ER(−)-MDA-MB-231 breast cancer cell lines. The results demonstrated that the presence of the anti-estrogenic component in the hybrid compound was critical for selectivity and cytotoxicity in ER(+)-MCF-7 human breast cancer cells as the hybrid was ~70-fold more potent than doxorubicin in inhibition of cell proliferation and promoting cell death. PMID:22404783

  7. 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...

  8. 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.

  9. 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...

  10. 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

  11. 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...

  12. 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...

  13. 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...

  14. 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.

  15. 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)...

  16. 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...

  17. 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…

  18. 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

  19. Measuring and Analyzing the Scholarly Impact of Experimental Evaluation Initiatives

    DEFF Research Database (Denmark)

    Angelini, Marco; Ferro, Nicola; Larsen, Birger;

    2014-01-01

    Evaluation initiatives have been widely credited with contributing highly to the development and advancement of information access systems, by providing a sustainable platform for conducting the very demanding activity of comparable experimental evaluation in a large scale. Measuring the impact o......, a methodology for measuring their scholarly impact, and tools exploiting visual analytics to analyze the outcomes....

  20. Initial Evaluation of the Patient with Suspected Epilepsy.

    Science.gov (United States)

    Jetté, Nathalie; Wiebe, Samuel

    2016-05-01

    The initial evaluation of the patient with suspected epilepsy is multifaceted and includes a careful history, diagnostic evaluation (EEG and brain imaging) and prompt referral to an epilepsy specialist to clarify seizure types and epilepsy syndrome. Screening for mental health conditions also should be considered, along with neurocognitive testing when deficits of language, memory, learning, attention, or executive function are present or when MRI shows involvement of brain regions implicated in cognitive function. In this review, we examine the approach to the initial evaluation of those with new-onset unprovoked seizures and possible epilepsy. PMID:27086982

  1. 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 ...

  2. 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

  3. Electrorefining cell evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Bronson, M.C.; Thomas, R.L. (ed.)

    1989-04-14

    Operational characteristics of the LANL electrorefining cell, a modified LANL electrorefining cell, and an advanced electrorefining cell (known as the CRAC cell) were determined. Average process yields achieved were: 75% for the LANL cell, 82% for the modified LANL cell, and 86% for the CRAC cell. All product metal from the LANL and modified LANL cells was within foundry specifications. Metal from one run in the CRAC cell exceeded foundry specifications for tantalum. The LANL and modified LANL cells were simple in design and operation, but product separation was more labor intensive than with the CRAC cell. The CRAC cell was more complicated in design but remained relatively simple in operation. A decision analysis concluded that the modified LANL cell was the preferred cell. It was recommended that the modified LANL cell be implemented by the Plutonium Recovery Project at Rocky Flats and that development of the CRAC cell continue. 8 refs., 22 figs., 12 tabs.

  4. Disseminated intravascular large-cell lymphoma with initial presentation mimicking Guillain-Barré syndrome.

    Science.gov (United States)

    Jiang, Qin Li; Pytel, Peter; Rowin, Julie

    2010-07-01

    We report a patient with intravascular large B-cell lymphoma who initially presented with acute ascending weakness and sensory changes. Electrodiagnostic testing and cerebral spinal fluid (CSF) studies were initially suggestive of a demyelinating polyneuropathy. Further clinical evaluation and testing were consistent with mononeuropathy multiplex. Autopsy revealed disseminated intravascular large-cell lymphoma. Intravascular large-cell lymphoma should be considered in the differential diagnosis of a rapidly evolving neuropathy associated with other organ involvement.

  5. 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…

  6. 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.

  7. 28 CFR 549.63 - Initial medical evaluation and management.

    Science.gov (United States)

    2010-07-01

    ... MANAGEMENT MEDICAL SERVICES Hunger Strikes, Inmate § 549.63 Initial medical evaluation and management. (a... hunger strike: (1) Measure and record height and weight; (2) Take and record vital signs; (3) Urinalysis... weight and vital signs at least once every 24 hours while the inmate is on a hunger strike....

  8. 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)

  9. 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.

  10. Evaluating the Initiation of Novel Oral Anticoagulants in Medicare Beneficiaries

    Science.gov (United States)

    Baik, Seo Hyon; Hernandez, Inmaculada; Zhang, Yuting

    2016-01-01

    BACKGROUND As alternatives to warfarin, 2 novel oral anticoagulants (NOACs), dabigatran and rivaroxaban, were approved in 2010 and 2011 to prevent stroke and other thromboembolic events in patients with atrial fibrillation. It is unclear how patient characteristics are associated with the initiation of anticoagulants. OBJECTIVE To evaluate how patient demographics, clinical characteristics, types of insurance, and patient out-of-pocket spending affect the initiation of warfarin and 2 NOACs—dabigatran and rivaroxaban. METHODS We used pharmacy claims data from a 5% random sample of Medicare beneficiaries to identify patients who were newly diagnosed with atrial fibrillation between October 1, 2010, and October 31, 2012, and who were prescribed an oral anticoagulant within 60 days of diagnosis. We identified key predictors of initiation of NOACs using a multinomial logistic regression model with generalized logit link. RESULTS Patients who were black and who had a history of acute myocardial infarction, stroke or transient ischemic attack, chronic kidney disease, or congestive heart failure were significantly associated with lower odds of receiving NOACs compared with warfarin. Age greater than 65 years, a history of hypertension, and use of nonsteroidal anti-inflammatory drugs were positively associated with the initiation of NOACs. Rivaroxaban was most likely to be initiated among women, followed by warfarin and dabigatran. Individuals receiving a low-income subsidy were more likely to initiate warfarin than NOACs, even though they paid little copayment. Individuals with supplemental Part D drug coverage, such as national Programs for All-Inclusive Care for the Elderly or employer-sponsored plans, were more likely to initiate NOACs compared with warfarin. CONCLUSIONS We found that race, sex, type of Part D plans, and some clinical conditions were associated with the initiation of NOACs relative to warfarin. But patient demographic and clinical characteristics did

  11. 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.

  12. Initial embryology and pluripotent stem cells in the pig

    DEFF Research Database (Denmark)

    Secher, Jan Ole Bertelsen; Callesen, Henrik; Freude, Kristine;

    2016-01-01

    to produce genetically modified mice since the mid-80s. However, no convincing reports on the generation of bona fide porcine embryonic stem cells or embryonic germ cells resulted from these activities, and with the advent of somatic cell nuclear transfer during the late 90s, alternative methods for creating......The quest for porcine pluripotent stem cells (PSCs) was initiated in the early 90s. Initially, it was the intention to benefit from these cells for production of genetically modified pigs using homologous recombination followed by derivation of chimeric offspring; a technology that has been used...... genetically modified pigs emerged. Over the past years, renewed interest in porcine PSCs has sparked activities in deriving in particular porcine induced pluripotent stem cells to develop the pig as a faithful model for studying the potentials and risks associated with induced pluripotent stem cell...

  13. [Initial evaluation and management of paroxysmal supraventricular tachycardia].

    Science.gov (United States)

    Rujic, Dragana; Sundbøll, Jens; Tofig, Bawer Jalal; Nielsen, Jens Cosedis; Pareek, Manan

    2016-01-18

    The paroxysmal supraventricular tachycardias (SVT) are commonly encountered arrhythmias and include atrioventricular nodal re-entrant tachycardia, atrioventricular reciprocating tachycardia, and focal atrial tachycardia. These tachycardias share several clinical features as well as similar management strategies. The probable mechanism of paroxysmal SVT can often be diagnosed from the clinical findings and a 12-lead ECG. This review describes the initial evaluation and treatment of patients with paroxysmal SVT, including distinctive features from the most important differential diagnoses.

  14. 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.

  15. Economic gains stimulate negative evaluations of corporate sustainability initiatives

    Science.gov (United States)

    Makov, Tamar; Newman, George E.

    2016-09-01

    In recent years, many organizations have sought to align their financial goals with environmental ones by identifying strategies that maximize profits while minimizing environmental impacts. Examples of this `win-win' approach can be found across a wide range of industries, from encouraging the reuse of hotel towels, to the construction of energy efficient buildings, to the large-scale initiatives of multi-national corporations. Although win-win strategies are generally thought to reflect positively on the organizations that employ them, here we find that people tend to respond negatively to the notion of profiting from environmental initiatives. In fact, observers may evaluate environmental win-wins less favourably than profit-seeking strategies that have no environmental benefits. The present studies suggest that how those initiatives are communicated to the general public may be of central importance. Therefore, organizations would benefit from carefully crafting the discourse around their win-win initiatives to ensure that they avoid this type of backlash.

  16. Glioma-initiating cells and molecular pathology: implications for therapy.

    Science.gov (United States)

    Natsume, Atsushi; Kinjo, Sayano; Yuki, Kanako; Kato, Takenori; Ohno, Masasuke; Motomura, Kazuya; Iwami, Kenichiro; Wakabayashi, Toshihiko

    2011-02-01

    There is now compelling evidence that gliomas harbor a small population of cells, termed glioma-initiating cells (GICs), characterized by their ability to undergo self-renewal and initiate tumorigenesis. The development of therapeutic strategies targeted toward GIC signaling may improve the treatment of malignant gliomas. The characterization of GICs provides a clue to elucidating histological heterogeneity and treatment failure. The role of the stem cell marker CD133 in the initiation and progression of brain tumors is still uncertain. Here, we review some of the signaling mechanisms involved in GIC biology, such as phosphatase and tensin homolog (PTEN), sonic hedgehog, Notch, and WNT signaling pathways, maternal embryonic leucine-zipper kinase (MELK), BMI1, and Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling. In addition, we discuss the role of microRNAs in GICs by focusing on microRNA-21 regulation by type I interferon.

  17. 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.

  18. Evaluating time dynamics of topographic threshold relations for gully initiation

    Science.gov (United States)

    Hayas, Antonio; Vanwalleghem, Tom; Poesen, Jean

    2016-04-01

    Gully erosion is one of the most important soil degradation processes at global scale. However, modelling of gully erosion is still difficult. Despite advances in the modelling of gully headcut rates and incision rates, it remains difficult to predict the location of gully initiation points and trajectories. In different studies it has been demonstrated that a good method of predicting gully initiation is by using a slope (S) - area (A) threshold. Such an S-A relation is a simple way of estimating the critical discharges needed to generate a critical shear stress that can incise a particular soil and initiate a gully. As such, the simple S-A threshold will vary if the rainfall-runoff behaviour of the soil changes or if the soil's erodibility changes. Over the past decades, important agronomic changes have produced significant changes in the soil use and soil management in SW Spain. It is the objective of this research to evaluate how S-A relations for gully initiation have changed over time and for two different land uses, cereal and olive. Data was collected for a gully network in the Cordoba Province, SW Spain. From photo-interpretation of historical air photos between 1956 and 2013, the gully network and initiation points were derived. In total 10 different time steps are available (1956; 1977; 1984; 1998; 2001; 2004; 2006; 2008; 2010; 2013). Topographical thresholds were extracted by combining the digitized gully network with the DEM. Due to small differences in the alignment of ortophotos and DEM, an optimization technique was developed in GIS to extract the correct S-A value for each point. With the S-A values for each year, their dynamics was evaluated as a function of land use (olive or cereal) and in function of the following variables in each of the periods considered: • soil management • soil cover by weeds, where weed growth was modeled from the daily soil water balance • rainfall intensity • root cohesion, , where root growth was modeled from

  19. 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.

  20. 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...

  1. Evaluating Maori community initiatives to promote healthy eating, healthy action.

    Science.gov (United States)

    Hamerton, Heather; Mercer, Christine; Riini, Denise; McPherson, Brighid; Morrison, Laurie

    2014-03-01

    Māori, the indigenous people of Aotearoa New Zealand, experience poorer health than non-Māori across a range of health measures. Interventions focused at an individual level have proved largely ineffective; 'bottom-up' approaches where communities determine their own priorities may be more sustainable than 'top-down' approaches where goals are determined by health authorities. The purpose of this paper is to illustrate an innovative health promotion programme aimed at improving Māori health and to discuss the importance of ownership and control of health initiatives by Māori. Evaluators conducted a comprehensive evaluation of a Healthy Eating Healthy Action programme in six small Māori health agencies, gathering information from programme managers and co-ordinators, participants and wider community members about what changes were occurring at individual, family and community levels. Effective interventions built on cultural values and practices and were delivered by Māori with close connections to the community. Changes in nutrition and physical activity made by participants also benefitted their wider families and community. The changes demonstrated subtle but important shifts in thinking about healthy eating and healthy activity that in the longer term could lead to more measurable change towards improved quality of life for people within communities.

  2. 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....... A pathlossbased solution limits such reconfigurations but also leads to a higher residual interference than the ID-based solution. An hybrid solution is shown to be an effective trade-off between the two former approaches....

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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...

  8. 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.

  9. 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.

  10. Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells

    Directory of Open Access Journals (Sweden)

    Lee HC

    2013-06-01

    Full Text Available Hsin-chung Lee,1,2 Qing-Dong Ling,1,3 Wan-Chun Yu,4 Chunh-Ming Hung,4 Ta-Chun Kao,4 Yi-Wei Huang,4 Akon Higuchi3–51Graduate Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taoyuan, 2Department of Surgery, Cathay General Hospital, Da'an District, Taipei, 3Cathay Medical Research Institute, Cathay General Hospital, Hsi-Chi City, Taipei, 4Department of Chemical and Materials Engineering, National Central University, Jhongli, Taoyuan, Taiwan; 5Department of Reproduction, National Research Institute for Child Health and Development, Okura, Tokyo, JapanPurpose: We evaluated the higher levels of carcinoembryonic antigen (CEA secreted by the LoVo human colon carcinoma cells in a medium containing anticancer drugs. Drug-resistant LoVo cells were analyzed by subcutaneously xenotransplanting them into mice. The aim of this study was to evaluate whether the drug-resistant cells isolated in this study were cancer-initiating cells, known also as cancer stem cells (CSCs.Methods: The production of CEA was investigated in LoVo cells that were cultured with 0–10 mM of anticancer drugs, and we evaluated the increase in CEA production by the LoVo cells that were stimulated by anticancer drug treatment. The expression of several CSC markers in LoVo cells treated with anticancer drugs was also evaluated. Following anticancer drug treatment, LoVo cells were injected subcutaneously into the flanks of severe combined immunodeficiency mice in order to evaluate the CSC fraction.Results: Production of CEA by LoVo cells was stimulated by the addition of anticancer drugs. Drug-resistant LoVo cells expressed lower levels of CSC markers, and LoVo cells treated with any of the anticancer drugs tested did not generate tumors within 8 weeks from when the cells were injected subcutaneously into severe combined immunodeficiency mice. These results suggest that the drug-resistant LoVo cells have a smaller population of CSCs than the

  11. 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

  12. 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

  13. 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…

  14. 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

  15. 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

  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. LGR5 and Nanog identify stem cell signature of pancreas beta cells which initiate pancreatic cancer.

    Science.gov (United States)

    Amsterdam, Abraham; Raanan, Calanit; Schreiber, Letizia; Polin, Nava; Givol, David

    2013-04-01

    Pancreas cancer, is the fourth leading cause of cancer death but its cell of origin is controversial. We compared the localization of stem cells in normal and cancerous pancreas using antibodies to the stem cell markers Nanog and LGR5. Here we show, for the first time, that LGR5 is expressed in normal pancreas, exclusively in the islets of Langerhans and it is co-localized, surprisingly, with Nanog and insulin in clusters of beta cells. In cancerous pancreas Nanog and LGR5 are expressed in the remaining islets and in all ductal cancer cells. We observed insulin staining among the ductal cancer cells, but not in metastases. This indicates that the islet's beta cells, expressing LGR5 and Nanog markers are the initiating cells of pancreas cancer, which migrated from the islets to form the ductal cancerous tissue, probably after mutation and de-differentiation. This discovery may facilitate treatment of this devastating cancer.

  18. 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)

  19. Development and Initial Evaluation of a Measure of Writing Anxiety.

    Science.gov (United States)

    Petzel, Thomas P.; Wenzel, Marc U.

    A Writing Anxiety Scale (WAS) was developed. A literature review and interviews with writing instructors identified nine components of writing behavior (Empathy, Expression, Evaluation by Others, Motivation, Organization, Procrastination, Self-Esteem, Technical Skills, and Writing Anxiety). A pool of 146 items were written to reflect the…

  20. 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

  1. 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...

  2. 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

  3. 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)

  4. 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.

  5. 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.

  6. 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.

  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. 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

  11. 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.

  12. Tip cell-derived RTK signaling initiates cell movements in the Drosophila stomatogastric nervous system anlage.

    Science.gov (United States)

    González-Gaitán, M; Jäckle, H

    2000-10-01

    The stomatogastric nervous system (SNS) of Drosophila is a simply organized neural circuitry that innervates the anterior enteric system. Unlike the central and the peripheral nervous systems, the SNS derives from a compact epithelial anlage in which three invagination centers, each giving rise to an invagination fold headed by a tip cell, are generated. Tip cell selection involves lateral inhibition, a process in which Wingless (Wg) activity adjusts the range of Notch signaling. Here we show that RTK signaling mediated by the Drosophila homolog of the epidermal growth factor receptor, DER, plays a key role in two consecutive steps during early SNS development. Like Wg, DER signaling participates in adjusting the range of Notch-dependent lateral inhibition during tip cell selection. Subsequently, tip cells secrete the DER ligand Spitz and trigger local RTK signaling, which initiates morphogenetic movements resulting in the tip cell-directed invaginations within the SNS anlage.

  13. 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...

  14. 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

  15. 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...

  16. 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)

  17. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells

    DEFF Research Database (Denmark)

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

    2016-01-01

    growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8......) 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....... 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....

  18. 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

  19. Initial Comparisons between the Advanced Technology Development Gen 2 Baseline Cells and Variant C Cells

    Energy Technology Data Exchange (ETDEWEB)

    Christophersen, Jon Petter; Motloch, Chester George; Wright, Randy Ben; Murphy, Timothy Collins; Belt, Jeffrey R; Ho, Chinh Dac; Bloom, Ira D.; Jones, S. A.; Battaglia, Vincent S.; Jungst, Rudy G.; Case, Herb L.; Sutula, Raymond A.; Barnes, James A.; Duong, Tien Q.

    2002-06-01

    The Advanced Technology Development Program is testing a second generation of lithium-ion cells, consisting of a baseline and three variant chemistries. The cathode composition of the Variant C chemistry was altered with an increase to the aluminum dopant and a decrease to the cobalt dopant to explore the impact on performance. However, it resulted in a 20% drop in rated capacity. Also, the Variant C average power fade is higher, but capacity fade is higher for the Baseline cell chemistry. Initial results indicate that the Variant C chemistry will reach end of life sooner than the Baseline chemistry.

  20. 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

  1. Selection of the best initial orbital elements of satellite based on fuzzy integration evaluation method

    Institute of Scientific and Technical Information of China (English)

    Yang Yong'an; Zhang Hongwei; Feng Zuren; Luo Yongjin

    2006-01-01

    The fuzzy integration evaluation method (FIEM) is studied in order to select the best orbital elements from the multi-group initial orbits determined by a satellite TT&C (Tracking, Telemetry and Control) center with all kinds of data sources. By employing FIEM together with the experience of TT&C experts, the index system to evaluate the selection of the best initial orbits is established after the data sources and orbit determination theories are studied. Besides, the concrete steps in employing the method are presented. Moreover, by taking the objects to be evaluated as evaluation experts, the problem of how to generate evaluation matrices is solved. Through practical application, the method to select the best initial orbital elements has been proved to be flexible and effective. The originality of the method is to find a new evaluation criterion (comparing the actually tracked orbits) replacing the traditional one (comparing the nominal orbits) for selecting the best orbital elements.

  2. 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

  3. 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

  4. Clinical Evaluation of the PCA3 Assay in Guiding Initial Biopsy Decisions

    NARCIS (Netherlands)

    A. de la Taille; J. Irani; M. Graefen; F. Chun; T. de Reijke; P. Kil; P. Gontero; A. Mottaz; A. Haese

    2011-01-01

    Purpose: We evaluated the clinical utility of the PCA3 assay in guiding initial biopsy decisions in prostate cancer. Materials and Methods: A European, prospective, multicenter study enrolled men with a serum total prostate specific antigen of 2.5 to 10 ng/ml scheduled for initial biopsy. After digi

  5. 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…

  6. 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.

  7. 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

  8. 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...

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. 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.

  14. YAP/TEAD co-activator regulated pluripotency and chemoresistance in ovarian cancer initiated cells.

    Directory of Open Access Journals (Sweden)

    Yan Xia

    Full Text Available Recent evidence suggests that some solid tumors, including ovarian cancer, contain distinct populations of stem cells that are responsible for tumor initiation, growth, chemo-resistance, and recurrence. The Hippo pathway has attracted considerable attention and some investigators have focused on YAP functions for maintaining stemness and cell differentiation. In this study, we successfully isolated the ovarian cancer initiating cells (OCICs and demonstrated YAP promoted self-renewal of ovarian cancer initiated cell (OCIC through its downstream co-activator TEAD. YAP and TEAD families were required for maintaining the expression of specific genes that may be involved in OCICs' stemness and chemoresistance. Taken together, our data first indicate that YAP/TEAD co-activator regulated ovarian cancer initiated cell pluripotency and chemo-resistance. It proposed a new mechanism on the drug resistance in cancer stem cell that Hippo-YAP signal pathway might serve as therapeutic targets for ovarian cancer treatment in clinical.

  15. Integrating a Comparison Group Design into a Theory of Change Evaluation: The Case of the Urban Health Initiative.

    Science.gov (United States)

    Weitzman, Beth C.; Silver, Diana; Dillman, Keri-Nicole

    2002-01-01

    Strengthened the theory of change approach to evaluating a complex social initiative by integrating it with a quasi-experimental comparison group design. Used the approach in an evaluation of the Robert Wood Johnson Foundation's Urban Health Initiative. Initial findings support the usefulness of the initiative. (SLD)

  16. 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,...

  17. 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

  18. 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.

  19. 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...

  20. 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

  1. 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...

  2. 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...

  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. 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....

  5. 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…

  6. 49 CFR 40.297 - Does anyone have the authority to change a SAP's initial evaluation?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Does anyone have the authority to change a SAP's... the Return-to-Duty Process § 40.297 Does anyone have the authority to change a SAP's initial... managed-care provider, any service agent) may change in any way the SAP's evaluation or...

  7. 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…

  8. 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

  9. 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

  10. 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…

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. Human placenta-derived mesenchymal progenitor cells support culture expansion of long-term culture-initiating cells from cord blood CD34+ cells

    Institute of Scientific and Technical Information of China (English)

    YiZhanga; ChangdongLi; XiaoxiaJiang; ShuangxiZhang; YingWu; BingLiu; PeihsienTang; NingMao

    2005-01-01

    Objective. Allogeneic transplantation with umbilical cord blood (UCB) in adult recipients is limited mainly by a low CD34+ cell dose. To overcome this shortcoming, human placenta as a novel source of human mesenchymal progenitor cell (MPC) was incorporated in an attempt to expand CD34+ ceils from UCB in vitro.Materials and Methods. Human placenta MPC was isolated and characterized by morphologic,immunophenotypical, and functional analysis. UCB CD34+ cells were expanded by coculturewith placeutal MPC. Suitable aliquots of cells were used to monitor cell production, elonogenie activity, and tong-term culture-initiating culture (LTC-IC) output. Finally, the immunoregulatory effect of placental MPC was evaluated by T-cell proliferation assay.Results. In its undifferentiated state, placental MPC displayed fibroblastoid morphology; was CD73, CD105, CD29, CD44, HLA-ABC, and CD166 positive; produced fibronectin, laminin,and vimentin; but was negative for CD14, CD31, CD34, CD45, HLA-DR, and α-smooth muscle actin. Functionally, it could be induced into adipocytes, osteocytes, and chondrocytes.In vitro expansion of UCB hematopoietic cells, when cocultured with placental MPC in the presence of eytokines, was significantly enhanced: CD34+ cells by 14.89±2.32 fold; colonyforming cell (CFC) by 36.73±5.79 told; and LTC-IC by 7.43±2.66 fold. Moreover, placental MPC could suppress T-cell proliferation induced by cellular stimuli.Conclusion. These results strongly suggest that human placental MPC may be a suitable feeder layer for expansion of hematopoietic progenitors from UCB in vitro.

  19. 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.

  20. Neo-lymphoid aggregates in the adult liver can initiate potent cell-mediated immunity.

    Directory of Open Access Journals (Sweden)

    Melanie Greter

    2009-05-01

    Full Text Available Subcutaneous immunization delivers antigen (Ag to local Ag-presenting cells that subsequently migrate into draining lymph nodes (LNs. There, they initiate the activation and expansion of lymphocytes specific for their cognate Ag. In mammals, the structural environment of secondary lymphoid tissues (SLTs is considered essential for the initiation of adaptive immunity. Nevertheless, cold-blooded vertebrates can initiate potent systemic immune responses even though they lack conventional SLTs. The emergence of lymph nodes provided mammals with drastically improved affinity maturation of B cells. Here, we combine the use of different strains of alymphoplastic mice and T cell migration mutants with an experimental paradigm in which the site of Ag delivery is distant from the site of priming and inflammation. We demonstrate that in mammals, SLTs serve primarily B cell priming and affinity maturation, whereas the induction of T cell-driven immune responses can occur outside of SLTs. We found that mice lacking conventional SLTs generate productive systemic CD4- as well as CD8-mediated responses, even under conditions in which draining LNs are considered compulsory for the initiation of adaptive immunity. We describe an alternative pathway for the induction of cell-mediated immunity (CMI, in which Ag-presenting cells sample Ag and migrate into the liver where they induce neo-lymphoid aggregates. These structures are insufficient to support antibody affinity maturation and class switching, but provide a novel surrogate environment for the initiation of CMI.

  1. 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: ...

  2. The Alpha Stem Cell Clinic: a model for evaluating and delivering stem cell-based therapies.

    Science.gov (United States)

    Trounson, Alan; DeWitt, Natalie D; Feigal, Ellen G

    2012-01-01

    Cellular therapies require the careful preparation, expansion, characterization, and delivery of cells in a clinical environment. There are major challenges associated with the delivery of cell therapies and high costs that will limit the companies available to fully evaluate their merit in clinical trials, and will handicap their application at the present financial environment. Cells will be manufactured in good manufacturing practice or near-equivalent facilities with prerequisite safety practices in place, and cell delivery systems will be specialized and require well-trained medical and nursing staff, technicians or nurses trained to handle cells once delivered, patient counselors, as well as statisticians and database managers who will oversee the monitoring of patients in relatively long-term follow-up studies. The model proposed for Alpha Stem Cell Clinics will initially use the capacities and infrastructure that exist in the most advanced tertiary medical clinics for delivery of established bone marrow stem cell therapies. As the research evolves, they will incorporate improved procedures and cell preparations. This model enables commercialization of medical devices, reagents, and other products required for cell therapies. A carefully constructed cell therapy clinical infrastructure with the requisite scientific, technical, and medical expertise and operational efficiencies will have the capabilities to address three fundamental and critical functions: 1) fostering clinical trials; 2) evaluating and establishing safe and effective therapies, and 3) developing and maintaining the delivery of therapies approved by the Food and Drug Administration, or other regulatory agencies.

  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. 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.

  6. Evaluation and measurement for improvement in service-level quality improvement initiatives.

    Science.gov (United States)

    Russell, Nicholas C C; Wallace, Louise M; Ketley, Diane

    2011-11-01

    The National Health Service (NHS) in England, as with other health services worldwide, currently faces the need to reduce costs and to improve the quality of patient care. Evidence gathered through effective and appropriate measurement and evaluation, is essential to achieving this. Through interviews with service improvement managers and analysis of comments in a seminar of NHS staff involved in health service improvement, we found a lack of understanding regarding the definition and methodology of both measurement and evaluation, which decreases the likelihood that NHS staff will be competent to commission or provide these skills. In addition, we highlight the importance of managers assessing their organizations' 'readiness' to undergo change before embarking on a quality improvement (QI) initiative, to ensure that the initiative's impact can be adequately judged. We provide definitions of measurement for improvement and of evaluation, and propose a comparative framework from which to gauge an appropriate approach. Examples of two large-scale QI initiatives are also given, along with descriptions of some of their problems and solutions, to illustrate the use of the framework. We recommend that health service managers use the framework to determine the most appropriate approach to evaluation and measurement for improvement for their context, to ensure that their decisions are evidence based.

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

    Energy Technology Data Exchange (ETDEWEB)

    Klymenko, Olena

    2014-02-26

    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).

  9. 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.

  10. 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.

  11. 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.

  12. 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...

  13. 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

  14. 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

  15. 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

    This study assessed cell voltage development, electricity recovery, and microbial community composition in response to initial substrate including acetate, xylose, acetate/xylose 1:1 mixture (ace/xyl), and bioethanol effluent (BE)during microbial fuel cell (MFC) operation at 1000Ω external...... 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....... However, BE-initiated MFCs only generated 162±1 mV. The acetate-initiated MFCs exhibited longer adaptation time (21 h) and lower cell voltage (645±10 mV) when the substrate was switched to xylose, whereas substrate switching to BE produced the highest voltage (656 mV), maximumpower density (362±27 mW/m2...

  16. 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...

  17. Metformin, a diabetes drug, eliminates tumor-initiating hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Tomoko Saito

    Full Text Available Metformin has been widely used as an oral drug for diabetes mellitus for approximately 60 years. Interestingly, recent reports showed that metformin exhibited an anti-tumor action in a wide range of malignancies including hepatocellular carcinoma (HCC. In the present study, we investigated its impact on tumor-initiating HCC cells. Metformin suppressed cell growth and induced apoptosis in a dose-dependent manner. Flow cytometric analysis showed that metformin treatment markedly reduced the number of tumor-initiating epithelial cell adhesion molecule (EpCAM(+ HCC cells. Non-adherent sphere formation assays of EpCAM(+ cells showed that metformin impaired not only their sphere-forming ability, but also their self-renewal capability. Consistent with this, immunostaining of spheres revealed that metformin significantly decreased the number of component cells positive for hepatic stem cell markers such as EpCAM and α-fetoprotein. In a xenograft transplantation model using non-obese diabetic/severe combined immunodeficient mice, metformin and/or sorafenib treatment suppressed the growth of tumors derived from transplanted HCC cells. Notably, the administration of metformin but not sorafenib decreased the number of EpCAM(+ cells and impaired their self-renewal capability. As reported, metformin activated AMP-activated protein kinase (AMPK through phosphorylation; however its inhibitory effect on the mammalian target of rapamycin (mTOR pathway did not necessarily correlate with its anti-tumor activity toward EpCAM(+ tumor-initiating HCC cells. These results indicate that metformin is a promising therapeutic agent for the elimination of tumor-initiating HCC cells and suggest as-yet-unknown functions other than its inhibitory effect on the AMPK/mTOR pathway.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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...

  5. 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

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Ninna Aggerholm-Pedersen

    2016-01-01

    Full Text Available 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 treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. 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.

  8. 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

  9. 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.

  10. 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...

  11. 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

  12. 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.

  13. 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

  14. 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...

  15. Matrix metalloproteinase-10 is required for lung cancer stem cell maintenance, tumor initiation and metastatic potential.

    Directory of Open Access Journals (Sweden)

    Verline Justilien

    Full Text Available 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. Interestingly, clonal expansion of Mmp10 deficient oncospheres can be restored by addition of exogenous Mmp10 protein to the culture medium, demonstrating a direct role for Mmp10 in the proliferation of these cells. Oncospheres exhibit enhanced tumor-initiating and metastatic activity when injected orthotopically into syngeneic mice, whereas Mmp10-deficient cultures show a severe defect in tumor initiation. Conversely, oncospheres implanted into syngeneic non-transgenic or Mmp10(-/- mice show no significant difference in tumor initiation, growth or metastasis, demonstrating the importance of Mmp10 produced by cancer cells rather than the tumor microenvironment in lung tumor initiation and maintenance. Analysis of gene expression data from human cancers reveals a strong positive correlation between tumor Mmp10 expression and metastatic behavior in many human tumor types. Thus, Mmp10 is required for maintenance of a highly tumorigenic, cancer-initiating, metastatic stem-like cell population in lung cancer. Our data demonstrate for the first time that Mmp10 is a critical lung cancer stem cell gene and novel therapeutic target for lung cancer stem cells.

  16. 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

  17. 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

  18. 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...

  19. 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....

  20. 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

  1. 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

  2. Large heterogeneity of mitochondrial DNA transcription and initiation of replication exposed by single-cell imaging.

    Science.gov (United States)

    Chatre, Laurent; Ricchetti, Miria

    2013-02-15

    Mitochondrial DNA (mtDNA) replication and transcription are crucial for cell function, but these processes are poorly understood at the single-cell level. We describe a novel fluorescence in situ hybridization protocol, called mTRIP (mitochondrial transcription and replication imaging protocol), that reveals simultaneously mtDNA and RNA, and that can also be coupled to immunofluorescence for in situ protein examination. mTRIP reveals mitochondrial structures engaged in initiation of DNA replication by identification of a specific sequence in the regulatory D-loop, as well as unique transcription profiles in single human cells. We observe and quantify at least three classes of mitochondrial structures: (i) replication initiation active and transcript-positive (Ia-Tp); (ii) replication initiation silent and transcript-positive (Is-Tp); and (iii) replication initiation silent and transcript-negative (Is-Tn). Thus, individual mitochondria are dramatically heterogeneous within the same cell. Moreover, mTRIP exposes a mosaic of distinct nucleic acid patterns in the D-loop, including H-strand versus L-strand transcripts, and uncoupled rRNA transcription and mtDNA initiation of replication, which might have functional consequences in the regulation of the mtDNA. Finally, mTRIP identifies altered mtDNA processing in cells with unbalanced mtDNA content and function, including in human mitochondrial disorders. Thus, mTRIP reveals qualitative and quantitative alterations that provide additional tools for elucidating the dynamics of mtDNA processing in single cells and mitochondrial dysfunction in diseases.

  3. Initiation of oncogenic transformation in human mammary epithelial cells by charged particles

    Science.gov (United States)

    Yang, T. C.; Georgy, K. A.; Craise, L. M.; Durante, M.

    1997-01-01

    Experimental studies have shown that high linear-energy transfer (LET) charged particles can be more effective than x-rays and gamma-rays in inducing oncogenic transformation in cultured cells and tumors in animals. Based on these results, experiments were designed and performed with an immortal human mammary epithelial cell line (H184B5), and several clones transformed by heavy ions were obtained. Cell fusion experiments were subsequently done, and results indicate that the transforming gene(s) is recessive. Chromosome analysis with fluorescence in situ hybridization (FISH) techniques also showed additional translocations in transformed human mammary epithelial cells. In addition, studies with these cell lines indicate that heavy ions can effectively induce deletion, break, and dicentrics. Deletion of tumor suppressor gene(s) and/or formation of translocation through DNA double strand breaks is a likely mechanism for the initiation of oncogenic transformation in human mammary epithelial cells.

  4. RK2 plasmid dynamics in Caulobacter crescentus cells--two modes of DNA replication initiation.

    Science.gov (United States)

    Wegrzyn, Katarzyna; Witosinska, Monika; Schweiger, Pawel; Bury, Katarzyna; Jenal, Urs; Konieczny, Igor

    2013-06-01

    Undisturbed plasmid dynamics is required for the stable maintenance of plasmid DNA in bacterial cells. In this work, we analysed subcellular localization, DNA synthesis and nucleoprotein complex formation of plasmid RK2 during the cell cycle of Caulobacter crescentus. Our microscopic observations showed asymmetrical distribution of plasmid RK2 foci between the two compartments of Caulobacter predivisional cells, resulting in asymmetrical allocation of plasmids to progeny cells. Moreover, using a quantitative PCR (qPCR) method, we estimated that multiple plasmid particles form a single fluorescent focus and that the number of plasmids per focus is approximately equal in both swarmer and predivisional Caulobacter cells. Analysis of the dynamics of TrfA-oriV complex formation during the Caulobacter cell cycle revealed that TrfA binds oriV primarily during the G1 phase, however, plasmid DNA synthesis occurs during the S and G2 phases of the Caulobacter cell cycle. Both in vitro and in vivo analysis of RK2 replication initiation in C. crescentus cells demonstrated that it is independent of the Caulobacter DnaA protein in the presence of the longer version of TrfA protein, TrfA-44. However, in vivo stability tests of plasmid RK2 derivatives suggested that a DnaA-dependent mode of plasmid replication initiation is also possible.

  5. 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.

  6. 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)

  7. 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

    to support the back-propagation of the evoked somatic action potential to produce the second dendritic spike. In summary, the balance of spatially distributed excitatory and inhibitory inputs can dynamically switch the mitral cell firing among four different modes: axo-somatic initiation with back...

  8. 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.

  9. 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,...

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. Fine tuning of IRF-4 expression by SWAP-70 controls the initiation of plasma cell development.

    Science.gov (United States)

    Chopin, Michaël; Chacón-Martínez, Carlos Andrés; Jessberger, Rolf

    2011-10-01

    The generation of plasma cells (PCs) is key for proper humoral immune responses. The transcription factors IRF-4 and BLIMP-1 (B-lymphocyte induce maturation protein-1) control PC commitment, but the underlying regulatory mechanisms are incompletely understood. Here we have identified SWAP-70 as being critically involved in Toll-like receptor (TLR)-triggered PC differentiation. Upon activation through various TLRs, Swap-70(-/-) B cells were activated and proliferated normally. However, expression of BLIMP-1 was markedly reduced and PC differentiation was impaired. Four hours of LPS stimulation were sufficient to drive PC differentiation, and SWAP-70 was required during this initial period. Swap-70(-/-) B cells pre-activated in vitro failed to efficiently differentiate into PCs upon adoptive transfer into recipient mice. Re-introduction of SWAP-70 into Swap-70(-/-) B cells rescued their development into PCs, and SWAP-70 over-expression in wild-type (WT) B cells increased PC generation. In the absence of SWAP-70, IRF-4 protein levels were reduced and the IRF-4(high) B220(+) CD138(-) compartment, including PC precursors, was strongly diminished. Ectopic expression of SWAP-70 increases IRF-4 protein levels and PC differentiation in WT and Swap-70(-/-) B cells, and IRF-4 over-expression in Swap-70(-/-) B cells elevates PC differentiation to WT levels. Thus, in a dose-dependent manner, SWAP-70 controls IRF-4 protein expression and thereby regulates the initiation of PC differentiation.

  15. 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

    2015-12-15

    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 cells in NSCLC.

  16. Decitabine Treatment of Glioma-Initiating Cells Enhances Immune Recognition and Killing

    Science.gov (United States)

    Riccadonna, Cristina; Yacoub Maroun, Céline; Vuillefroy de Silly, Romain; Boehler, Margaux; Calvo Tardón, Marta; Jueliger, Simone; Taverna, Pietro; Barba, Leticia; Marinari, Eliana; Pellegatta, Serena; Bassoy, Esen Yonca; Martinvalet, Denis; Dietrich, Pierre-Yves; Walker, Paul R.

    2016-01-01

    Malignant gliomas are aggressive brain tumours with very poor prognosis. The majority of glioma cells are differentiated (glioma-differentiated cells: GDCs), whereas the smaller population (glioma-initiating cells, GICs) is undifferentiated and resistant to conventional therapies. Therefore, to better target this pool of heterogeneous cells, a combination of diverse therapeutic approaches is envisaged. Here we investigated whether the immunosensitising properties of the hypomethylating agent decitabine can be extended to GICs. Using the murine GL261 cell line, we demonstrate that decitabine augments the expression of the death receptor FAS both on GDCs and GICs. Interestingly, it had a higher impact on GICs and correlated with an enhanced sensitivity to FASL-mediated cell death. Moreover, the expression of other critical molecules involved in cognate recognition by cytotoxic T lymphocytes, MHCI and ICAM-1, was upregulated by decitabine treatment. Consequently, T-cell mediated killing of both GDCs and GICs was enhanced, as was T cell proliferation after reactivation. Overall, although GICs are described to resist classical therapies, our study shows that hypomethylating agents have the potential to enhance glioma cell recognition and subsequent destruction by immune cells, regardless of their differentiation status. These results support the development of combinatorial treatment modalities including epigenetic modulation together with immunotherapy in order to treat heterogenous malignancies such as glioblastoma. PMID:27579489

  17. 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

  18. 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

  19. 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

  20. 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.)

  1. 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.)

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. MRI-guided percutaneous laser ablation of small renal cell carcinoma: Initial clinical experience

    Energy Technology Data Exchange (ETDEWEB)

    Kariniemi, Juho; Ojala, Risto; Hellstroem, Pekka; Sequeiros, Roberto Blanco (Dept. of Radiology, Dept. of Surgery, Oulu Univ. Hospital, Oulu (Finland)), e-mail: juho.kariniemi@oulu.fi

    2010-05-15

    Background: The number of detected small renal cell carcinomas (RCCs) has been rising, largely due to advances in imaging. Open surgical resection is the standard management of small RCCs; however, imaging-guided percutaneous ablative therapies have emerged as a minimally invasive treatment alternative, especially for patients who are poor candidates for surgery. Purpose: To evaluate the initial clinical experience of magnetic resonance imaging (MRI)-guided percutaneous laser ablation of small RCCs. Material and Methods: Eight patients with 10 tumors were treated with percutaneous MRI-guided laser ablation. All tumors (diameter range 1.5-3.8 cm, mean 2.7 cm) were biopsy-proven RCCs. By using a 0.23 T open MRI system and general anesthesia in patients, one to four (mean 2.6) laser fibers were placed and the tumors were ablated under near real-time MRI control by observing the signal void caused by the temperature change in the heated tissue. The treatment was considered successful if the tumor showed no contrast enhancement at follow-up imaging. Results: All except one tumor were successfully ablated in one session. The first patient treated showed enhancing residual tumor in post-procedural MRI; she has thus far declined retreatment. One complication, a myocardial infarction, occurred; all other patients tolerated the procedure well. No local recurrence was discovered during the follow-up (range 12-30 months, mean 20 months). Conclusion: In this small group of patients with relatively short follow-up period, MRI-guided percutaneous laser ablation proved to be a promising treatment option for small RCCs

  8. 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

  9. 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.

  10. 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

  11. CK2 phosphorylation of eukaryotic translation initiation factor 5 potentiates cell cycle progression

    Science.gov (United States)

    Homma, Miwako Kato; Wada, Ikuo; Suzuki, Toshiyuki; Yamaki, Junko; Krebs, Edwin G.; Homma, Yoshimi

    2005-01-01

    Casein kinase 2 (CK2) is a ubiquitous eukaryotic Ser/Thr protein kinase that plays an important role in cell cycle progression. Although its function in this process remains unclear, it is known to be required for the G1 and G2/M phase transitions in yeast. Here, we show that CK2 activity changes notably during cell cycle progression and is increased within 3 h of serum stimulation of quiescent cells. During the time period in which it exhibits high enzymatic activity, CK2 associates with and phosphorylates a key molecule for translation initiation, eukaryotic translation initiation factor (eIF) 5. Using MS, we show that Ser-389 and -390 of eIF5 are major sites of phosphorylation by CK2. This is confirmed using eIF5 mutants that lack CK2 sites; the phosphorylation levels of mutant eIF5 proteins are significantly reduced, relative to WT eIF5, both in vitro and in vivo. Expression of these mutants reveals that they have a dominant-negative effect on phosphorylation of endogenous eIF5, and that they perturb synchronous progression of cells through S to M phase, resulting in a significant reduction in growth rate. Furthermore, the formation of mature eIF5/eIF2/eIF3 complex is reduced in these cells, and, in fact, restricted diffusional motion of WT eIF5 was almost abolished in a GFP-tagged eIF5 mutant lacking CK2 phosphorylation sites, as measured by fluorescence correlation spectroscopy. These results suggest that CK2 may be involved in the regulation of cell cycle progression by associating with and phosphorylating a key molecule for translation initiation. PMID:16227438

  12. 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.)

  13. 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

  14. 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)

  15. Decisive role of apurinic/apyrimidinic endonuclease/Ref-1 in initiation of cell death.

    Science.gov (United States)

    Cho, Kyoung Joo; Kim, Hyun Jeong; Park, Soo Chul; Kim, Hyun Woo; Kim, Gyung Whan

    2010-11-01

    The apurinic/apyrimidinic endonuclease/redox effector factor-1 (APE/Ref-1) is involved in the base excision repair of apurinic/apyrimidinic sites induced by oxidative DNA damage. APE/Ref-1 was decreased by kainic acid (KA) injury in a time-dependent manner at the level of proteins, not transcripts. We investigated whether alteration of APE/Ref-1 amounts would influence hippocampal cell fate, survival or death, after KA injury. Overexpression of APE/Ref-1 using adenovirus and restoration of APE small peptides significantly reduced KA-induced hippocampal cell death. Both silencing of APE/Ref-1 by siRNA and inhibition of endonuclease by an antibody significantly increased caspase-3 activity and apoptotic cell death triggered from the early time after exposure to KA. These findings suggest that cell death is initiated by reducing APE/Ref-1 protein and inhibiting its repair function in spite of enough protein amounts. In conclusion, APE/Ref-1 may be a regulator of cell death initiation, and APE small peptides could provide molecular mechanism-based therapies for neuroprotection in progressive excitotoxic neuronal damage.

  16. [The Langerhans cell histiocytosis with thymic localization as initial and exclusive place].

    Science.gov (United States)

    Hernández Pérez, J M; Franquet Casas, T; Rodríguez, S; Giménez, A

    2007-10-01

    The Langerhans' cell histiocytosis (LCH), also known as Histiocitosis X it is an illness not very frequent granulomatosus etiology not clarified yet, that it can have different manifestations and localizations, however the thymic localization as initial and exclusive place gives presentation HCL it is quite unusual. The present case is presented a patient that debuted with a clinical unspecific, where the tests give image they put she gives apparent a mass in previous mediastinum and that after the pathologic and immunohistochemical analysis they evidenced a proliferation Langerhans s cells and eosinophils it being positive for CD1a and S-100 confirming the diagnosis of the LCH.

  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 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

  19. 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 < .001), billboards/posters/wall hangings (marginal effect: 2.09, p < .05), and FP on the television (marginal effect: 2.46, p < .001) were significantly more likely to be using a modern method at endline. In addition, we found borderline significance for being exposed to a community health worker (marginal effect: 1.66, p < .10) and living close to an improved public and private supply environment where UHI undertook activities (marginal effects and p values: 2.48, p < .05 and 1.56, p < .10, respectively). Conclusions UHI program activities were designed to complement the Government of 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

  20. 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

  1. 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

  2. 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...

  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. 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...

  5. 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 ...

  6. Evaluation of Initial Telomere Length and Changes after Transplantation in Adult Double-Unit Cord Blood Transplant Recipients.

    Science.gov (United States)

    Ashbridge, Beth; Zehir, Ahmet; Lubin, Marissa; Barker, Juliet N; Moore, Malcolm A S

    2015-07-01

    Cord blood (CB) leukocytes have inherent telomere length (TL) variation, and CB hematopoietic stem cells (HSC) can maintain high telomerase levels preventing telomere attrition in vitro. We evaluated TL changes in 13 adult double-unit CB transplant (CBT) recipients. In the 26 units, we observed a marked variation in CB TL at thaw (median, 9.99 kilobases [kb]; range, 6.85 to 13.5). All 13 patients engrafted. Of 11 engrafting with 1 unit, there was no correlation between unit dominance and TL (mean dominant unit TL, 8.84 kb ± 1.76; mean nonengrafting unit TL, 10.3 kb ± 1.81; P = .77). Serial measurements of TL up to 1 year after CBT demonstrated an overall mean 3.04 kb ± .16 TL decrease with only 1 patient exhibiting telomere maintenance. In summary, initial TL does not predict CB unit dominance. Moreover, our analysis suggests neonatal hematopoiesis makes a transition to an HSC characterized by changes in average TL and potentially low telomerase asymmetric cell division in adult CBT recipients. Further investigation of alterations in telomere length and its clinical implications after transplantation of this observation are indicated.

  7. 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...

  8. 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.

  9. 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.

  10. Cross talk Initiated by Endothelial Cells Enhances Migration and Inhibits Anoikis of Squamous Cell Carcinoma Cells through STAT3/Akt/ERK Signaling

    Directory of Open Access Journals (Sweden)

    Kathleen G. Neiva

    2009-06-01

    Full Text Available It is well known that cancer cells secrete angiogenic factors to recruit and sustain tumor vascular networks. However, little is known about the effect of endothelial cell-secreted factors on the phenotype and behavior of tumor cells. The hypothesis underlying this study is that endothelial cells initiate signaling pathways that enhance tumor cell survival and migration. Here, we observed that soluble mediators from primary human dermal microvascular endothelial cells induce phosphorylation of signal transducer and activator of transcription 3 (STAT3, Akt, and extracellular signal-regulated kinase (ERK in a panel of head and neck squamous cell carcinoma (HNSCC cells (OSCC-3, UM-SCC-1, UM-SCC-17B, UM-SCC-74A. Gene expression analysis demonstrated that interleukin-6 (IL- 6, interleukin-8 (CXCL8, and epidermal growth factor (EGF are upregulated in endothelial cells cocultured with HNSCC. Blockade of endothelial cell-derived IL-6, CXCL8, or EGF by gene silencing or neutralizing antibodies inhibited phosphorylation of STAT3, Akt, and ERK in tumor cells, respectively. Notably, activation of STAT3, Akt, and ERK by endothelial cells enhanced migration and inhibited anoikis of tumor cells. We have previously demonstrated that Bcl-2 is upregulated in tumor microvessels in patients with HNSCC. Here, we observed that Bcl-2 signaling induces expression of IL-6, CXCL8, and EGF, providing a mechanism for the upregulation of these cytokines in tumor-associated endothelial cells. This study expands the contribution of endothelial cells to the pathobiology of tumor cells. It unveils a new mechanism in which endothelial cells function as initiators of molecular crosstalks that enhance survival and migration of tumor cells.

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

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    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.

  12. 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

    2016-08-01

    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 ~>1010-fold expansion) with both high growth rate (~20-fold expansion/7 days) and high volumetric yield (~2.0 × 107 cells/ml) without the loss of stemness. The scalable method can be used to produce sufficient, affordable glioblastoma TICs for drug discovery.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. Evaluation of a well-established task-shifting initiative: the lay counselor cadre in Botswana.

    Directory of Open Access Journals (Sweden)

    Jenny H Ledikwe

    Full Text Available BACKGROUND: Evidence supports the implementation of task shifting to address health worker shortages that are common in resource-limited settings. However, there is need to learn from established programs to identify ways to achieve the strongest, most sustainable impact. This study examined the Botswana lay counselor cadre, a task shifting initiative, to explore effectiveness and contribution to the health workforce. METHODS: This evaluation used multiple methods, including a desk review, a national lay counselor survey (n = 385; response = 94%, in-depth interviews (n = 79, lay counselors focus group discussions (n = 7, lay counselors observations (n = 25, and client exit interviews (n = 47. RESULTS: Interview and focus group data indicate that lay counselors contribute to essentially all HIV-related programs in Botswana and they conduct the majority of HIV tests and related counseling at public health facilities throughout the country. Interviews showed that the lay counselor cadre is making the workload of more skilled health workers more manageable and increasing HIV acceptance in communities. The average score on a work-related knowledge test was 74.5%. However for 3 questions, less than half answered correctly. During observations, lay counselors demonstrated average competence for most skills assessed and clients (97.9% were satisfied with services received. From the survey, lay counselors generally reported being comfortable with their duties; however, some reported clinical duties that extended beyond their training and mandate. Multiple factors affecting the performance of the lay counselors were identified, including insufficient resources, such as private counseling space and HIV test kits; and technical, administrative, and supervisory support. CONCLUSION: Lay counselors are fulfilling an important role in Botswana's healthcare system, serving as the entry point into HIV care, support, and treatment services

  18. 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.

  19. 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

  20. [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

  1. Tumor senescence and radioresistant tumor-initiating cells (TICs): let sleeping dogs lie!

    Science.gov (United States)

    Zafarana, Gaetano; Bristow, Robert G

    2010-01-01

    Preclinical data from cell lines and experimental tumors support the concept that breast cancer-derived tumor-initiating cells (TICs) are relatively resistant to ionizing radiation and chemotherapy. This could be a major determinant of tumor recurrence following treatment. Increased clonogenic survival is observed in CD24-/low/CD44+ TICs derived from mammosphere cultures and is associated with (a) reduced production of reactive oxygen species, (b) attenuated activation of γH2AX and CHK2-p53 DNA damage signaling pathways, (c) reduced propensity for ionizing radiation-induced apoptosis, and (d) altered DNA double-strand or DNA single-strand break repair. However, recent data have shed further light on TIC radioresistance as irradiated TICs are resistant to tumor cell senescence following DNA damage. Taken together, the cumulative data support a model in which DNA damage signaling and repair pathways are altered in TICs and lead to an altered mode of cell death with unique consequences for long-term clonogen survival. The study of TIC senescence lays the foundation for future experiments in isogenic models designed to directly test the capacity for senescence and local control (that is, not solely local regression) and spontaneous metastases following treatment in vivo. The study also supports the targeting of tumor cell senescence pathways to increase TIC clonogen kill if the targeting also maintains the therapeutic ratio.

  2. 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

  3. Toll-like receptor 11-initiated innate immune response in male mouse germ cells.

    Science.gov (United States)

    Chen, Qiaoyuan; Zhu, Weiwei; Liu, Zhenghui; Yan, Keqin; Zhao, Shutao; Han, Daishu

    2014-02-01

    Toxoplasma gondii and uropathogenic Escherichia coli (UPEC) may infect the testis and impair testicular function. Mechanisms underlying testicular innate immune response to these two pathogens remain to be clarified. The present study examined the function of TLR11, which can be recognized by T. gondii-derived profilin and UPEC, in initiating innate immune response in male mouse germ cells. TLR11 is predominantly expressed in spermatids. Profilin and UPEC induced the expressions of different inflammatory cytokine profiles in the germ cells. In particular, profilin induced the expressions of macrophage chemotactic protein 1 (MCP1), interleukin 12 (IL12), and interferon gamma (IFNG) through nuclear factor KB (NFKB) activation. UPEC induced the expressions of MCP1, IL12, and IFNG, as well as tumor necrosis factor alpha (TNFA), IL6, and IFNB, through the activation of NFKB, IFN regulatory factor 3, and mitogen-activated protein kinases. Evidence showed that profilin induced the innate response in male germ cells through TLR11 signaling, and UPEC triggered the response through TLR11 and other TLR-signaling pathways. We also provided evidence that local injection of profilin or UPEC induces the innate immune response in the germ cells. Data describe TLR11-mediated innate immune function of male germ cells in response to T. gondii profilin and UPEC stimulations. This system may play a role in testicular defense against T. gondii and UPEC infections in mice.

  4. Formative Evaluation for a Healthy Corner Store Initiative in Pitt County, North Carolina: Engaging Stakeholders for a Healthy Corner Store Initiative, Part 2

    Directory of Open Access Journals (Sweden)

    Katherine K. Lawton, MPH

    2013-07-01

    Full Text Available Introduction We examined the feasibility of increasing access to healthful food in corner stores to inform a Communities Putting Prevention to Work (CPPW initiative by engaging stakeholders (corner store owners and customers in a formative evaluation. Methods Qualitative interviews were conducted with corner store owners and managers (n = 11. Customer intercept surveys (n = 179 were also conducted with customers of 9 stores. Corner stores were located in rural food deserts (municipalities without a chain supermarket and in low-income, urban municipalities in eastern North Carolina. Interviews were transcribed verbatim and double-coded. Qualitative themes related to feasibility of increasing access to healthful foods were extracted. Shopping patterns of rural and urban customers were compared by using t tests. Results Corner store owners were willing to stock more healthful foods, but they perceived that customer demand for these foods was low. Rural customers reported more frequently shopping at corner stores than urban customers and more frequently stated that the reason they do not eat more fruits and vegetables is that the stores in which they shop do not sell them. Most customers reported they would be very or somewhat likely to purchase fresh produce at a corner store. Conclusion Corner stores may be an important source of food for rural and low-income residents and thus a good place in which to intervene. The results of this formative evaluation were used to plan and evaluate a CPPW healthy corner store initiative.

  5. 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.

  6. 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.

  7. 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...

  8. 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.

  9. 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.

  10. 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.)

  11. A prospective study of PET/CT in initial staging of small-cell lung cancer

    DEFF Research Database (Denmark)

    Fischer, B M; Mortensen, J; Langer, S W;

    2007-01-01

    BACKGROUND: Small-cell lung cancer (SCLC) accounts for 15%-20% of all lung cancer cases. Accurate and fast staging is mandatory when choosing treatment, but current staging procedures are time consuming and lack sensitivity. PATIENTS AND METHODS: A prospective study was designed to examine the role...... of combined positron emission tomography/computed tomography (PET/CT) compared with standard staging (CT, bone scintigraphy and immunocytochemical assessment of bone marrow biopsy) of patients with SCLC. Thirty-four consecutive patients were included. Twenty-nine patients received initial PET/CT. RESULTS: PET...

  12. 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

  13. STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity.

    Science.gov (United States)

    Demaria, Olivier; De Gassart, Aude; Coso, Sanja; Gestermann, Nicolas; Di Domizio, Jeremy; Flatz, Lukas; Gaide, Olivier; Michielin, Olivier; Hwu, Patrick; Petrova, Tatiana V; Martinon, Fabio; Modlin, Robert L; Speiser, Daniel E; Gilliet, Michel

    2015-12-15

    Spontaneous CD8 T-cell responses occur in growing tumors but are usually poorly effective. Understanding the molecular and cellular mechanisms that drive these responses is of major interest as they could be exploited to generate a more efficacious antitumor immunity. As such, stimulator of IFN genes (STING), an adaptor molecule involved in cytosolic DNA sensing, is required for the induction of antitumor CD8 T responses in mouse models of cancer. Here, we find that enforced activation of STING by intratumoral injection of cyclic dinucleotide GMP-AMP (cGAMP), potently enhanced antitumor CD8 T responses leading to growth control of injected and contralateral tumors in mouse models of melanoma and colon cancer. The ability of cGAMP to trigger antitumor immunity was further enhanced by the blockade of both PD1 and CTLA4. The STING-dependent antitumor immunity, either induced spontaneously in growing tumors or induced by intratumoral cGAMP injection was dependent on type I IFNs produced in the tumor microenvironment. In response to cGAMP injection, both in the mouse melanoma model and an ex vivo model of cultured human melanoma explants, the principal source of type I IFN was not dendritic cells, but instead endothelial cells. Similarly, endothelial cells but not dendritic cells were found to be the principal source of spontaneously induced type I IFNs in growing tumors. These data identify an unexpected role of the tumor vasculature in the initiation of CD8 T-cell antitumor immunity and demonstrate that tumor endothelial cells can be targeted for immunotherapy of melanoma.

  14. Interdependence of initial cell density, drug concentration and exposure time revealed by real-time impedance spectroscopic cytotoxicity assay

    DEFF Research Database (Denmark)

    Caviglia, Claudia; Zor, Kinga; Canepa, Silvia;

    2015-01-01

    between the rate of cell death and the initial cell seeding density was found at 2.5 μM doxorubicin concentration, whereas this was not observed at 5 or 100 μM. By sensing the changes in the cell–substrate interaction using impedance spectroscopy under static conditions, the onset of cytotoxicity......We investigated the combined effect of the initial cell density (12 500, 35 000, 75 000, and 100 000 cells cm−2) and concentration of the anti-cancer drug doxorubicin on HeLa cells by performing timedependent cytotoxicity assays using real-time electrochemical impedance spectroscopy. A correlation...

  15. Mast cells are key mediators of cathelicidin-initiated skin inflammation in rosacea.

    Science.gov (United States)

    Muto, Yumiko; Wang, Zhenping; Vanderberghe, Matthieu; Two, Aimee; Gallo, Richard L; Di Nardo, Anna

    2014-11-01

    Rosacea is a chronic inflammatory skin disease whose pathophysiological mechanism is still unclear. However, it is known that mast cell (MC) numbers are increased in the dermis of rosacea patients. MC proteases not only recruit other immune cells, which amplify the inflammatory response, but also cause vasodilation and angiogenesis. MCs are also one of the primary sources of cathelicidin LL-37 (Cath LL-37), an antimicrobial peptide that has been shown to be an enabler of rosacea pathogenesis. Here, we demonstrate that MCs are key mediators of cathelicidin-initiated skin inflammation. After Cath LL-37 injection into the dermis, MC-deficient B6.Cg-Kit(W-sh)/HNihrJaeBsmJ (KitW-sh) mice did not develop rosacea-like features. Conversely, chymase (Prosacea subjects who showed a decrease in matrix metalloproteinase activity (Prosacea treatment.

  16. 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

  17. Evaluation of Melt Behavior with initial Melt Velocity under SFR Severe Accidents

    Energy Technology Data Exchange (ETDEWEB)

    Heo, Hyo; Bang, In Cheol [UNIST, Ulsan (Korea, Republic of); Jerng, Dong Wook [Chung-Ang Univ, Seoul (Korea, Republic of)

    2015-10-15

    In the current Korean sodium-cooled fast reactor (SFR) program, early dispersion of the molten metallic fuel within a subchannel is suggested as one of the inherent safety strategies for the initiating phase of hypothetical core disruptive accident (HCDA). The safety strategy provides negative reactivity driven by the melt dispersal, so it could reduce the possibility of the recriticality event under a severe triple or more fault scenario for SFR. Since the behavior of the melt dispersion is unpredictable, it depends on the accident condition, particularly core region. While the voided coolant channel region is usually developed in the inner core, the unvoided coolant channel region is formed in the outer core. It is important to confirm the fuel dispersion with the core region, but there are not sufficient existing studies for them. From the existing studies, the coolant vapor pressure is considered as one of driving force to move the melt towards outside of the core. There is a complexity of the phenomena during intermixing of the melt with the coolant after the horizontal melt injections. It is too difficult to understand the several combined mechanisms related to the melt dispersion and the fragmentation. Thus, it could be worthwhile to study the horizontal melt injections at lower temperature as a preliminary study in order to identify the melt dispersion phenomena. For this reason, it is required to clarify whether the coolant vapor pressure is the driving force of the melt dispersion with the core region. The specific conditions to be well dispersed for the molten metallic fuel were discussed in the experiments with the simulant materials. The each melt behavior was compared to evaluate the melt dispersion under the coolant void condition and the boiling condition. As the results, the following results are remarked: 1. The upward melt dispersion did not occur for a given melt and coolant temperature in the nonboiling range. Over current range of conditions

  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. {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.

  20. 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

  1. 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...

  2. 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

  3. Translation initiation of ornithine decarboxylase and nucleocytoplasmic transport of cyclin D1 mRNA are increased in cells overexpressing eukaryotic initiation factor 4E.

    Science.gov (United States)

    Rousseau, D; Kaspar, R; Rosenwald, I; Gehrke, L; Sonenberg, N

    1996-01-01

    The structure of m7GpppN (where N is any nucleotide), termed cap, is present at the 5' end of all eukaryotic cellular mRNAs (except organellar). The eukaryotic initiation factor 4E (eIF-4E) binds to the cap and facilitates the formation of translation initiation complexes. eIF-4E is implicated in control of cell growth, as its overexpression causes malignant transformation of rodent cells and deregulates HeLa cell growth. It was suggested that overexpression of eIF-4E results in the enhanced translation of poorly translated mRNAs that encode growth-promoting proteins. Indeed, enhanced expression of several proteins, including cyclin D1 and ornithine decarboxylase (ODC), was documented in eIF-4E-overexpressing NTH 3T3 cells. However, the mechanism underlying this increase has not been elucidated. Here, we studied the mode by which eIF-4E increases the expression of cyclin D1 and ODC. We show that the increase in the amount of cyclin D1 and ODC is directly proportional to the degree of eIF-4E overexpression. Two mechanisms, which are not mutually exclusive, are responsible for the increase. In eIF-4E-overexpressing cells the rate of translation initiation of ODC mRNA was increased inasmuch as the mRNA sedimented with heavier polysomes. For cyclin D1 mRNA, translation initiation was not increased, but rather its amount in the cytoplasm increased, without a significant increase in total mRNA. Whereas, in the parental NIH 3T3 cell line, a large proportion of the cyclin D1 mRNA was confined to the nucleus, in eIF-4E-overexpressing cells the vast majority of the mRNA was present in the cytoplasm. These results indicate that eIF-4E affects directly or indirectly mRNA nucleocytoplasmic transport, in addition to its role in translation initiation. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8577715

  4. 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.

  5. 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.

  6. 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.

  7. 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.)

  8. 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.)

  9. 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…

  10. Testing the Feasibility of Fidelity Evaluation in a Multisite, Multiprogram Initiative

    Science.gov (United States)

    Cornish, Disa Lubker; Losch, Mary E.; Avery, Mitchell

    2016-01-01

    Monitoring fidelity of implementation is a critical task when initiating evidence-based programs. This pilot study sought to identify best practices in a fidelity monitoring process and determine the feasibility of continuing a fidelity monitoring process with a multisite, multiprogram initiative. A fidelity log was created for each of 11…

  11. 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…

  12. 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

  13. 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...

  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. 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

  16. 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

  17. 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

  18. Evaluation of the Early Results of the Initial 500 Cardiac Operations Performed in a New Center

    Directory of Open Access Journals (Sweden)

    Turan Erdoğan

    2011-12-01

    Full Text Available Background: The initial 500 cases of a new center which is established in a province having no history of open heart surgery are evaluated with respect to mortality especially.Methods: A total of 500 patients underwent operations at our clinic between March 2008 and November 2009. Of these patients 373 (74.6% were male, 127 (25.4% were female and the mean age was 64.15±11.54. Four hundred eleven patients had coronary artery disease (19 had left ventricular aneurysm, 46 patients had coronary artery disease together with heart valve disease (of these 2 had ascending aortic aneurysm, 1 had left ventricular aneurysm, 1 had rupture of sinus valsalva aneurysm, 30 patients had valvular disease ( 1 had also patent ductus arteriosus, 4 patients had type 1 aortic dissection, 4 patients had ascending aortic aneurysm (3 had aortic valve disease, 4 patients had coarctation of the aorta, and 1 of the patients underwent surgery with the diagnosis of secundum atrial septal defect. Results: In-hospital mortality rate was 2% with 10 patients. The reasons of deaths were; low cardiac output in 3, renal insufficiency in 2, peroperative myocardial infarction in 2, bleeding in 1, lung complications in 1 and cardiac tamponade in 1. Fifteen patients (3% due to bleeding caused for surgical re-exploration. Postoperative atrial fibrillation developed in 97 patients (19.4%. Four patients (0.8% suffered wound infections on saphenous vein region, one patient (0.2% developed mediastinitis. Three patients (0.6% had neurological complications (two patients developed hemiplegia, one suffered from persistent tonic-clonic convultion. Prolonged entubation, prolonged intensive care unit stay and readmission to intensive care were other complications with rates of 20 (4%, 31(6.2% and 13(2.6% respectively. Conclusion: Our study showed that there is a strong relationship between peroperative myocard infarction and mortality, and patients who had diminished renal functions

  19. 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.

  20. [A framework for evaluating ethical issues of public health initiatives: practical aspects and theoretical implications].

    Science.gov (United States)

    Petrini, Carlo

    2015-01-01

    The "Framework for the Ethical Conduct of Public Health Initiatives", developed by Public Health Ontario, is a practical guide for assessing the ethical implications of evidence-generating public health initiatives, whether research or non-research activities, involving people, their biological materials or their personal information. The Framework is useful not only to those responsible for determining the ethical acceptability of an initiative, but also to investigators planning new public health initiatives. It is informed by a theoretical approach that draws on widely shared bioethical principles. Two considerations emerge from both the theoretical framework and its practical application: the line between practice and research is often blurred; public health ethics and biomedical research ethics are based on the same common heritage of values.

  1. 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.

  2. 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…

  3. 49 CFR 40.293 - What is the SAP's function in conducting the initial evaluation of an employee?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false What is the SAP's function in conducting the... Professionals and the Return-to-Duty Process § 40.293 What is the SAP's function in conducting the initial evaluation of an employee? As a SAP, for every employee who comes to you following a DOT drug and...

  4. 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.

  5. A Model for Statewide Evaluation of a Universal Positive Behavior Support Initiative

    Science.gov (United States)

    Elfner Childs, Karen; Kincaid, Don; George, Heather Peshak

    2010-01-01

    Several statewide evaluations of Tier 1/Universal Level Positive Behavior Support (PBS) implementation efforts have been conducted, adhering to the evaluation template developed by Horner, Sugai, and Lewis-Palmer in 2005. Building on these examples, Florida's Positive Behavior Support Project developed a comprehensive evaluation system that sought…

  6. 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

  7. Pathogenesis of idiopathic pulmonary fibrosis: from initial apoptosis of epithelial cells to lung remodeling?

    Institute of Scientific and Technical Information of China (English)

    JIN Hua-liang; DONG Jing-cheng

    2011-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal form of interstitial lung disease.Despite extensive efforts in research during recent years,the mechanisms of the disease remain poorly understood.Evidence of an inflammatory mechanism,both supportive and contrary,is briefly reviewed in this paper.However,growing evidence has indicated that the apoptosis of alveolar epithelial cells (AECs) may be the early driving force of progression,with subsequent disrupted integrity of the alveolar-capillary basement membrane leading to an abnormal wound healing pathway.Thus,this paper will focus on outlining a process of pathogenesis of IPF from initial apoptosis of AECs to end lung remodeling.

  8. 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.

  9. 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)

  10. 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

  11. 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...

  12. 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

  13. 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

  14. 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

  15. Novel population of small tumour-initiating stem cells in the ovaries of women with borderline ovarian cancer

    Science.gov (United States)

    Virant-Klun, Irma; Stimpfel, Martin

    2016-01-01

    Small stem cells with diameters of up to 5 μm previously isolated from adult human ovaries indicated pluripotency and germinal lineage, especially primordial germ cells, and developed into primitive oocyte-like cells in vitro. Here, we show that a comparable population of small stem cells can be found in the ovarian tissue of women with borderline ovarian cancer, which, in contrast to small stem cells in “healthy” ovaries, formed spontaneous tumour-like structures and expressed some markers related to pluripotency and germinal lineage. The gene expression profile of these small putative cancer stem cells differed from similar cells sorted from “healthy” ovaries by 132 upregulated and 97 downregulated genes, including some important forkhead box and homeobox genes related to transcription regulation, developmental processes, embryogenesis, and ovarian cancer. These putative cancer stem cells are suggested to be a novel population of ovarian tumour-initiating cells in humans. PMID:27703207

  16. Meiotic recombination initiated by a double-strand break in rad50{Delta} yeast cells otherwise unable to initiate meiotic recombination

    Energy Technology Data Exchange (ETDEWEB)

    Malkova, A.; Haber, J.E. [Brandeis Univ., Waltham, MA (United States); Dawson, D. [Tufts Univ., Boston, MA (United States)] [and others

    1996-06-01

    Meiotic recombination in Saccharomyces cerevisiae is initiated by double-strand breaks (DSBs). We have developed a system to compare the properties of meiotic DSBs with those created by the site-specific HO endonuclease. HO endonuclease was expressed under the control of the meiotic-specific SPO13 promoter, creating a DSB at a single site on one of yeast`s 16 chromosomes. In Rad{sup +} strains the times of appearance of the HO-induced DSBs and of subsequent recombinants are coincident with those induced by normal meiotic DSBs. Physical monitoring of DNA showed that SPO13::HO induced gene conversions both in Rad{sup +} and in rad50{Delta} cells that cannot initiate normal meiotic DSBs. We find that the RAD50 gene is important, but not essential, for recombination even after a DSB has been created in a meiotic cell. In rad50{Delta} cells, some DSBs are not repaired until a broken chromosome has been packaged into a spore and is subsequently germinated. This suggests that a broken chromosome does not signal an arrest of progression through meiosis. The recombination defect in rad50{Delta} diploids is not, however, meiotic specific, as mitotic rad50 diploids, experiencing an HO-induced DSB, exhibit similar departures from wild-type recombination. 57 refs., 5 figs., 3 tabs.

  17. Reconstitution of CD4 T Cells in Bronchoalveolar Lavage Fluid after Initiation of Highly Active Antiretroviral Therapy▿

    Science.gov (United States)

    Knox, Kenneth S.; Vinton, Carol; Hage, Chadi A.; Kohli, Lisa M.; Twigg, Homer L.; Klatt, Nichole R.; Zwickl, Beth; Waltz, Jeffrey; Goldman, Mitchell; Douek, Daniel C.; Brenchley, Jason M.

    2010-01-01

    The massive depletion of gastrointestinal-tract CD4 T cells is a hallmark of the acute phase of HIV infection. In contrast, the depletion of the lower-respiratory-tract mucosal CD4 T cells as measured in bronchoalveolar lavage (BAL) fluid is more moderate and similar to the depletion of CD4 T cells observed in peripheral blood (PB). To understand better the dynamics of disease pathogenesis and the potential for the reconstitution of CD4 T cells in the lung and PB following the administration of effective antiretroviral therapy, we studied cell-associated viral loads, CD4 T-cell frequencies, and phenotypic and functional profiles of antigen-specific CD4 T cells from BAL fluid and blood before and after the initiation of highly active antiretroviral therapy (HAART). The major findings to emerge were the following: (i) BAL CD4 T cells are not massively depleted or preferentially infected by HIV compared to levels for PB; (ii) BAL CD4 T cells reconstitute after the initiation of HAART, and their infection frequencies decrease; (iii) BAL CD4 T-cell reconstitution appears to occur via the local proliferation of resident BAL CD4 T cells rather than redistribution; and (iv) BAL CD4 T cells are more polyfunctional than CD4 T cells in blood, and their functional profile is relatively unchanged after the initiation of HAART. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might aid in the reconstitution of mucosal CD4 T cells. PMID:20610726

  18. 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

  19. Mitochondria-derived hydrogen peroxide selectively enhances T cell receptor-initiated signal transduction.

    Science.gov (United States)

    Gill, Tejpal; Levine, Alan D

    2013-09-01

    T cell receptor (TCR)-initiated signal transduction is reported to increase production of intracellular reactive oxygen species, such as superoxide (O2˙(-)) and hydrogen peroxide (H2O2), as second messengers. Although H2O2 can modulate signal transduction by inactivating protein phosphatases, the mechanism and the subcellular localization of intracellular H2O2 as a second messenger of the TCR are not known. The antioxidant enzyme superoxide dismutase (SOD) catalyzes the dismutation of highly reactive O2˙(-) into H2O2 and thus acts as an intracellular generator of H2O2. As charged O2˙(-) is unable to diffuse through intracellular membranes, cells express distinct SOD isoforms in the cytosol (Cu,Zn-SOD) and mitochondria (Mn-SOD), where they locally scavenge O2˙(-) leading to production of H2O2. A 2-fold organelle-specific overexpression of either SOD in Jurkat T cell lines increases intracellular production of H2O2 but does not alter the levels of intracellular H2O2 scavenging enzymes such as catalase, membrane-bound peroxiredoxin1 (Prx1), and cytosolic Prx2. We report that overexpression of Mn-SOD enhances tyrosine phosphorylation of TCR-associated membrane proximal signal transduction molecules Lck, LAT, ZAP70, PLCγ1, and SLP76 within 1 min of TCR cross-linking. This increase in mitochondrial H2O2 specifically modulates MAPK signaling through the JNK/cJun pathway, whereas overexpressing Cu,Zn-SOD had no effect on any of these TCR-mediated signaling molecules. As mitochondria translocate to the immunological synapse during TCR activation, we hypothesize this translocation provides the effective concentration of H2O2 required to selectively modulate downstream signal transduction pathways.

  20. 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.

  1. Meaningful, measurable, and manageable approaches to evaluating healthy food financing initiatives: an overview of resources and approaches.

    Science.gov (United States)

    Fleischhacker, Sheila E; Flournoy, Rebecca; Moore, Latetia V

    2013-01-01

    More than 23 million Americans have limited access to grocery stores. Healthy food financing initiatives have been emerging at local, state, and federal levels to address grocery gaps. Through public-private partnerships, retailers have been awarded funding to open or renovate a variety of food outlets. Preliminary findings have reported increased access to healthy foods, as well as improved community and economic development. As policy makers continue to consider enacting or expanding these initiatives and as all program stakeholders increasingly seek information on program impacts, this article provides guidance on using meaningful, measurable, and manageable methods to evaluate program's multifaceted outcomes.

  2. Classwide PBIS for Students with EBD: Initial Evaluation of an Integrity Tool

    Science.gov (United States)

    Jeffrey, Jennifer L.; McCurdy, Barry L.; Ewing, Sam; Polis, Dustin

    2009-01-01

    The purpose of this pilot project was to develop a tool and a process for providing performance feedback on evidence-based classroom management strategies to teachers of students in emotional support classrooms. The project was carried out with nine classroom teachers and descriptive results are discussed. Initial results found increases in…

  3. 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.

  4. 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

  5. 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.

  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. CD4+ T cell counts in initiation of antiretroviral therapy in HIV infected asymptomatic individuals; controversies and inconsistencies.

    Science.gov (United States)

    Maina, E K; Bonney, E Y; Bukusi, E A; Sedegah, M; Lartey, M; Ampofo, W K

    2015-12-01

    The primary goal when devising strategies to define the start of therapy in HIV infected individuals is to avoid HIV disease progression and toxicity from antiretroviral therapy (ART). Intermediate goals includes, avoiding resistance by suppressing HIV replication, reducing transmission, limiting spread and diversity of HIV within the body and protecting the immune system from harm. The question of how early or late to start ART and achieve both primary and intermediate goals has dominated HIV research. The distinction between early and late treatment of HIV infection is currently a matter of CD4+ T cells count, a marker of immune status, rather than on viral load, a marker of virus replication. Discussions about respective benefits of early or delayed therapy, as well as the best CD4+ T cell threshold during the course of HIV infection at which ART is initiated remains inconclusive. Guidelines issued by various agencies, provide different initiation recommendations. This can be confusing for clinicians and policy-makers when determining the best time to initiate therapy. Optimizing ART initiation strategies are clearly complex and must be balanced between individual and broader public health needs. This review assesses available data that contributes to the debate on optimal time to initiate therapy in HIV-infected asymptomatic individuals. We also review reports on CD4+ T cell threshold to guide initiation of ART and finally discuss arguments for and against early or late initiation of ART.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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...

  14. 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

  15. 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.)

  16. Initial Evaluation of Acoustic Emission SHM of PRSEUS Multi-bay Box Tests

    Science.gov (United States)

    Horne, Michael R.; Madaras, Eric I.

    2016-01-01

    A series of tests of the Pultruded Rod Stitched Efficient Unitized Structure (PRSEUS) HWB Multi-Bay Test Article were conducted during the second quarter of 2015 at NASA Langley Research Center (LaRC) in the Combined Loads Test facility (COLTS). This report documents the Acoustic Emission (AE) data collected during those tests along with an initial analysis of the data. A more detailed analysis will be presented in future publications.

  17. 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...

  18. Breast MRI for Evaluating Patients with Metastatic Axillary Lymph Node and Initially Negative Mammography and Sonography

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Eun Young; Han, Boo Kyung; Shin, Jung Hee; Kang, Seok Seon [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2007-10-15

    We wanted to investigate the ability of breast MR imaging to identify the primary malignancy in patients with axillary lymph node metastases and initially negative mammography and sonography, and we correlated those results with the conventional imaging. From September 2001 to April 2006, 12 patients with axillary lymph node metastases and initially negative mammography and sonography underwent breast MR imaging to identify occult breast carcinoma. We analyzed the findings of the MR imaging, the MR-correlated mammography and the second-look sonography. We followed up both the MR-positive and MR-negative patients. MR imaging detected occult breast carcinoma in 10 of 12 (83%) patients. Two MR-negative patients were free of carcinoma in the ipsilateral breast during their follow-up period (39 and 44 months, respectively). In nine out of 10 patients, the MR-correlated mammography and second-look sonography localized lesions that were not detected on the initial exam. All the non-MR-correlated sonographic abnormalities were benign. Breast MR imaging can identify otherwise occult breast cancer in patients with metastatic axillary lymph nodes. Localization of the lesions through MR-correlated mammography and second-look sonography is practically feasible in most cases.

  19. Evaluating methamphetamine use and risks of injection initiation among street youth: the ARYS study

    Directory of Open Access Journals (Sweden)

    Montaner Julio SG

    2006-05-01

    Full Text Available Abstract Many Canadian cities are experiencing ongoing infectious disease and overdose epidemics among injection drug users (IDU. These health concerns have recently been exacerbated by the increasing availability and use of methamphetamine. The challenges of reducing health-related harms among IDU have led to an increased recognition that strategies to prevent initiation into injection drug use must receive renewed focus. In an effort to better explore the factors that may protect against or facilitate entry into injection drug use, the At Risk Youth Study (ARYS has recently been initiated in Vancouver, Canada. The local setting is unique due to the significant infrastructure that has been put in place to reduce HIV transmission among active IDU. The ARYS study will seek to examine the impact of these programs, if any, on non-injection drug users. In addition, Vancouver has been the site of widespread use of methamphetamine in general and has seen a substantial increase in the use of crystal methamphetamine among street youth. Hence, the ARYS cohort is well positioned to examine the harms associated with methamphetamine use, including its potential role in facilitating initiation into injection drug use. This paper provides some background on the epidemiology of illicit drug use among street youth in North America and outlines the methodology of ARYS, a prospective cohort study of street youth in Vancouver, Canada.

  20. 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

  1. Lifetime evaluation for IASCC initiation of cold worked 316 stainless steel's BFB in PWR primary water

    Energy Technology Data Exchange (ETDEWEB)

    Takakura, K.; Nakata, K.; Ando, M. [Japan Nuclear Energy Safety Organization (JNES), Tokyo (Japan); Fujimoto, K.; Wachi, E. [Mitsubishi Heavy Industries (MHI) Ltd., Tokyo (Japan)

    2007-07-01

    IASCC (Irradiation Assisted Stress Corrosion Cracking) is a matter of great concern for degradation of core internal components in light water nuclear reactor. A Japanese National Project is currently in progress, aiming to establish a data base for plant life management (PLM) which contributes to lifetime evaluation of baffle former bolt (BFB) for operating periods up to 60 years. In this study, IASCC tests have been conducted on BFBs irradiated up to 20 dpa and flux thimble tubes (FTTs) irradiated up to 70 dpa removed from actual plants, which were made of cold worked 316 stainless steel. Constant load SCC initiation tests were carried out in simulated PWR primary water using C-ring type specimens. IASCC initiation time became shorter with increasing fluence and increasing applied stress. Furthermore, IASCC initiation was observed even in conditions where applied stress was much lower than {sigma}y (0.2% yield strength after irradiation). The IASCC threshold stresses became also lower with increasing fluence. Also, a novel method for evaluation of IASCC initiation lifetime for BFB has been proposed based on the SCC test data obtained in this project. (author)

  2. 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.

  3. 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...

  4. 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 ...

  5. 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 ...

  6. 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

  7. 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

  8. Implementation and evaluation of the HEROES initiative: a tri-state coordinated school health program to reduce childhood obesity.

    Science.gov (United States)

    King, Mindy H; Lederer, Alyssa M; Sovinski, Danielle; Knoblock, Heidi M; Meade, Rhonda K; Seo, Dong-Chul; Kim, Nayoung

    2014-05-01

    This article describes the design, implementation, and evaluative findings of the HEROES (Healthy, Energetic, Ready, Outstanding, Enthusiastic, Schools) Initiative, a school-based multilevel childhood obesity prevention intervention. Based on the Centers for Disease Control and Prevention's recommended coordinated school health approach, the HEROES Initiative works to alleviate the burden of childhood obesity in Southern Indiana, Northwestern Kentucky, and Southeastern Illinois in the United States. Process evaluation was conducted with the 17 participating schools in spring 2012 based on interviews with school personnel and observation of the school environment. Findings showed that despite some variability, schools were generally able to implement the intervention with fidelity. School-level outcome evaluation was also based on observation of the school environment, and revealed that schools had implemented a number of new practices to encourage physical activity and healthy eating. Assessment of student-level outcomes was based on professionally collected physiological measurements and self-reported behavioral data collected over an 18-month period of time, last collected in spring 2012. Findings demonstrated that the HEROES Initiative has been successful in reducing the percentage of overweight children in participating schools and healthfully modifying their dietary, physical activity, and sedentary behaviors. Strategies that have facilitated success and challenges related to the intervention are discussed. PMID:24334542

  9. 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.

  10. Analytical Method to Evaluate Hugoniot of Metallic Materials with Different Initial Temperatures

    Institute of Scientific and Technical Information of China (English)

    WANG Qing-Song; LAN Qiang; HU Jian-Bo; WU Jing; DAI Cheng-Da

    2008-01-01

    @@ An analytical method is proposed to evaluate the Hugoniot parameters of preheated metallic materials by relating to its principal Hugoniot.Modelling calculations for 1100 AI, Cu and Ta show that the preheating lowers to a certain extent the shock impedance and the degree of lowering the shock impedance increases with increasing pre-heating temperature.The Hugoniots of 6061-T6 AI and TC4 preheated flyers at known preheating temperatures are evaluated, and are utilized to calculate the particle velocity and shock pressure using the impedance-match method based on the measured shock wave velocity and impact velocity reported in Z pinch-driven and threestage gun-driven Hugoniot experiments.The presented method allows a reasonable evaluation for Hugoniot of the preheated metallic flyers.

  11. 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

  12. 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

  13. 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

    One of the parameters needed for characterizing soil hydraulic properties is the saturated water content. In the past, different techniques have been employed to obtain an initially fully saturated sample, but it is uncertain how successful the different techniques actually are in achieving full...... 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 sample was drained...

  14. 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

  15. Clinical utility of F-18 FDG PET-CT in the initial evaluation of lung cancer

    DEFF Research Database (Denmark)

    Madsen, Poul Henning; Holdgaard, Paw Christian; Christensen, Janne Buck;

    2016-01-01

    , and pre-operative evaluation, we conducted a systematic literature search, review, and quality assessment using the rapid evidence assessment toolkit and the Oxford Centre for Evidence-Based Medicine methodology. The literature search resulted in 4,208 records including 918 reviews, of which 139 met...... the predefined criteria and were read in full to identify relevant original articles on F-18 FDG PET-CT (1) in the evaluation of solitary pulmonary nodules (n = 14), (2) in curative-intent treatment trials (n = 9), and (3) in planning of invasive procedures (n = 18). RESULTS: We found the following important...

  16. 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.

  17. Initiation of an inflammatory response in resident intestinal lamina propria cells -use of a human organ culture model.

    Directory of Open Access Journals (Sweden)

    Jutta Schröder-Braunstein

    Full Text Available Resident human lamina propria immune cells serve as powerful effectors in host defense. Molecular events associated with the initiation of an intestinal inflammatory response in these cells are largely unknown. Here, we aimed to characterize phenotypic and functional changes induced in these cells at the onset of intestinal inflammation using a human intestinal organ culture model. In this model, healthy human colonic mucosa was depleted of epithelial cells by EDTA treatment. Following loss of the epithelial layer, expression of the inflammatory mediators IL1B, IL6, IL8, IL23A, TNFA, CXCL2, and the surface receptors CD14, TLR2, CD86, CD54 was rapidly induced in resident lamina propria cells in situ as determined by qRT-PCR and immunohistology. Gene microarray analysis of lamina propria cells obtained by laser-capture microdissection provided an overview of global changes in gene expression occurring during the initiation of an intestinal inflammatory response in these cells. Bioinformatic analysis gave insight into signalling pathways mediating this inflammatory response. Furthermore, comparison with published microarray datasets of inflamed mucosa in vivo (ulcerative colitis revealed a significant overlap of differentially regulated genes underlining the in vivo relevance of the organ culture model. Furthermore, genes never been previously associated with intestinal inflammation were identified using this model. The organ culture model characterized may be useful to study molecular mechanisms underlying the initiation of an intestinal inflammatory response in normal mucosa as well as potential alterations of this response in inflammatory bowel disease.

  18. 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

  19. [Development and psychometric evaluation of a Japanese version of the Personal Growth Initiative Scale-II].

    Science.gov (United States)

    Tokuyoshi, Yoga; Iwasaki, Syoichi

    2014-06-01

    We conducted two studies to develop a Japanese version of the Personal Growth Initiative Scale-II (PGIS-II), and examined its reliability and validity. PGIS-II was developed as a multidimensional measure of the multiple processes of the Personal Growth Initiative (PGI). The PGI describes an active, intentional engagement in the process of personal growth for self-improvement of life experiences. Study 1 (N = 204) reports the confirmatory factor analysis (CFA) of the Japanese version of the PGIS-II. The CFA confirmed that 4-factor model showed acceptable fit indices, with reliability coefficients ranging from .67 to .84. Concurrent validity of the PGIS-II was indicated by the correlation with happiness, the positive score for automatic thoughts. Study 2 (N = 101) reports the concurrent validity of the PGIS-II using scales for locus of control, self-esteem and coping. Results suggested significant correlations between scores on the PGIS-II and locus of control, self-esteem and some coping subscales. The overall results suggest that the Japanese version of the PGIS-II has satisfactory statistical reliability and validity. PMID:25016838

  20. 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

  1. 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).

  2. 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…

  3. "A Great Program...for Me as a Gramma": Caregivers Evaluate a Family Literacy Initiative

    Science.gov (United States)

    Anderson, Jim; Morrison, Fiona

    2007-01-01

    In this article, we report a study in which we asked 137 parents and caregivers to evaluate a year-long family literacy program in which they participated. Parents valued the insights they gained about children's learning in general and literacy development in particular. They reported that they learned from each other as well as from the program…

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. Sediment distribution modeling for evaluating the impact of initial structure on catchment hydrological behaviour

    Science.gov (United States)

    Maurer, T. J.; Gerke, H. H.; Hinz, C.

    2015-12-01

    Structural heterogeneity, namely the spatial distribution of soils and sediments (represented by mineral particles), characterizes catchment hydrological behavior. In natural catchments, local geology and the specific geomorphic processes determine the characteristics and spatial distribution of structures. In constructed catchments, structural features are determined primarily by the construction processes and the geological origin of the parent material. Objectives are scenarios of 3D catchment structures in form of complete 3D description of soil hydraulic properties generated from the knowledge of the formation processes. The constructed hydrological catchment 'Hühnerwasser' (Lower Lusatia, Brandenburg, Germany) was used for the calibration and validation of model results due to its well-known conditions. For the modeling of structural features, a structure generator was used to model i) quasi-deterministic sediment distributions using input data from a geological model of the parent material excavation site; ii) sediment distributions that are conditioned to measurement data from soil sampling; and iii) stochastic component sediment distributions. All three approaches allow a randomization within definable limits. Furthermore, the spoil cone / spoil ridge orientation, internal layering, surface compaction and internal spoil cone compaction were modified. These generated structural models were incorporated in a gridded 3D volume model constructed with the GOCAD software. The impact of structure variation was assessed by hydrological modeling with HYDRUS 2D/3D software. 3D distributions of soil hydraulic properties were estimated based on generated sediment properties using adapted pedotransfer functions. Results were compared with hydrological monitoring data. The impact of structural feature variation on hydrological behavior was analyzed by comparing different simulation scenarios. The established initial sediment distributions provide a basis for the

  9. 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...

  10. 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...

  11. 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.

  12. 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...

  13. 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...

  14. 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.

  15. 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.

  16. Red Blood Cell Fatty Acids and Incident Diabetes Mellitus in the Women's Health Initiative Memory Study.

    Directory of Open Access Journals (Sweden)

    William S Harris

    Full Text Available The relations between dietary and/or circulating levels of fatty acids and the development of type 2 diabetes is unclear. Protective associations with the marine omega-3 fatty acids and linoleic acid, and with a marker of fatty acid desaturase activity delta-5 desaturase (D5D ratio have been reported, as have adverse relations with saturated fatty acids and D6D ratio.To determine the associations between red blood cell (RBC fatty acid distributions and incident type 2 diabetes.Prospective observational cohort study nested in the Women's Health Initiative Memory Study.General population.Postmenopausal women.Self-reported incident type 2 diabetes.There were 703 new cases of type 2 diabetes over 11 years of follow up among 6379 postmenopausal women. In the fully adjusted models, baseline RBC D5D ratio was inversely associated with incident type 2 diabetes [Hazard Ratio (HR 0.88, 95% confidence interval (CI 0.81-0.95 per 1 SD increase. Similarly, baseline RBC D6D ratio and palmitic acid were directly associated with incident type 2 diabetes (HR 1.14, 95% CI 1.04-1.25; and HR 1.24, 95% CI 1.14-1.35, respectively. None of these relations were materially altered by excluding incident cases in the first two years of follow-up. There were no significant relations with eicosapentaenoic, docosahexaenoic or linoleic acids.Whether altered fatty acid desaturase activities or palmitic acid levels are causally related to the development of type 2 diabetes cannot be determined from this study, but our findings suggest that proportions of certain fatty acids in RBC membranes are associated with risk for type 2 diabetes.

  17. 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

  18. 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

  19. 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

  20. Global Positioning System Time Transfer Receiver (GPS/TTR) prototype design and initial test evaluation

    Science.gov (United States)

    Oaks, J.; Frank, A.; Falvey, S.; Lister, M.; Buisson, J.; Wardrip, C.; Warren, H.

    1982-01-01

    Time transfer equipment and techniques used with the Navigation Technology Satellites were modified and extended for use with the Global Positioning System (GPS) satellites. A prototype receiver was built and field tested. The receiver uses the GPS L1 link at 1575 MHz with C/A code only to resolve a measured range to the satellite. A theoretical range is computed from the satellite ephemeris transmitted in the data message and the user's coordinates. Results of user offset from GPS time are obtained by differencing the measured and theoretical ranges and applying calibration corrections. Results of the first field test evaluation of the receiver are presented.

  1. 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.

  2. 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.

  3. Cloud mask via cumulative discriminant analysis applied to satellite infrared observations: scientific basis and initial evaluation

    Directory of Open Access Journals (Sweden)

    U. Amato

    2014-06-01

    Full Text Available We introduce a classification method (Cumulative Discriminant Analysis of the Discriminant Analysis type to discriminate between cloudy and clear sky satellite observations in the thermal infrared. The tool is intended for the high spectral resolution infrared sounder (IRS planned for the geostationary METEOSAT (Meteorological Satellite Third Generation platform and uses IASI (Infrared Atmospheric Sounding Interferometer data as a proxy. The Cumulative Discriminant Analysis does not introduce biases intrinsic with the approximation of the probability density functions and is flexible enough to adapt to different strategies to optimize the cloud mask. The methodology is based on nine statistics computed from IASI spectral radiances, which exploit the high spectral resolution of the instrument and which effectively summarize information contained within the IASI spectrum. A Principal Component Analysis prior step is also introduced which makes the problem more consistent with the statistical assumptions of the methodology. An initial assessment of the scheme is performed based on global and regional IASI real data sets and cloud masks obtained from AVHRR (Advanced Very High Resolution Radiometer and SEVIRI (Spinning Enhanced Visible and Infrared Imager imagers. The agreement with these independent cloud masks is generally well above 80%, except at high latitudes in their winter seasons.

  4. 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.

  5. 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.

  6. Alport syndrome: significance of gingival biopsy in the initial diagnosis and periodontal evaluation after renal transplantation.

    Science.gov (United States)

    Toygar, Hilal Uslu; Toygar, Okan; Guzeldemir, Esra; Cilasun, Ulkem; Nacar, Ahmet; Bal, Nebil

    2009-01-01

    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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. Toehold-initiated rolling circle amplification for visualizing individual microRNAs in situ in single cells.

    Science.gov (United States)

    Deng, Ruijie; Tang, Longhua; Tian, Qianqian; Wang, Ying; Lin, Lei; Li, Jinghong

    2014-02-24

    The ability to quantitate and visualize microRNAs (miRNAs) in situ in single cells would greatly facilitate the elucidation of miRNA-mediated regulatory circuits and their disease associations. A toehold-initiated strand-displacement process was used to initiate rolling circle amplification of specific miRNAs, an approach that achieves both stringent recognition and in situ amplification of the target miRNA. This assay, termed toehold-initiated rolling circle amplification (TIRCA), can be utilized to identify miRNAs at physiological temperature with high specificity and to visualize individual miRNAs in situ in single cells within 3 h. TIRCA is a competitive candidate technique for in situ miRNA imaging and may help us to understand the role of miRNAs in cellular processes and human diseases in more detail.

  14. 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

  15. 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.

  16. 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.

  17. Cancer cell spheroids as a model to evaluate chemotherapy protocols.

    Science.gov (United States)

    Perche, Federico; Torchilin, Vladimir P

    2012-10-01

    To determine whether the spheroid culture can be used to evaluate drug efficacy, we have evaluated the toxicity of free or carrier-associated doxorubicin as a single drug or in combination with other antineoplastic agents using the spheroid cultures of drug-resistant cancer cells. Paclitaxel, cisplatin, dexamethasone, mitoxantrone, sclareol or methotrexate were used in combination with doxorubicin. The effect of the treatment protocols on free, micellar and liposomal doxorubicin accumulation in spheroids and on resulting toxicity was evaluated by fluorescence and lactate dehydrogenase release, respectively. Enhanced doxorubicin accumulation and toxicity were observed after spheroid pretreatment with mitoxantrone or paclitaxel. Effects of the drug combination with doxorubicin were sequence dependent, use of doxorubicin as the first drug being the least inducer of toxicity. Finally, spheroids were recognized by a cancer cell-specific antibody. Our results suggest the usefulness of spheroids to evaluate chemotherapy combinations. PMID:22892843

  18. 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.

  19. 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.

  20. 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).

  1. 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. 

  2. 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.

  3. 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.

  4. Cytotoxic evaluation of phenolic compounds from lichens against melanoma cells.

    Science.gov (United States)

    Brandão, Luiz Fabrício Gardini; Alcantara, Glaucia Braz; Matos, Maria de Fátima Cepa; Bogo, Danielle; Freitas, Deisy dos Santos; Oyama, Nathália Mitsuko; Honda, Neli Kika

    2013-01-01

    Atranorin, lichexanthone, and the (+)-usnic, diffractaic, divaricatic, perlatolic, psoromic, protocetraric, and norstictic acids isolated from the lichens Parmotrema dilatatum (VAIN.) HALE, Usnea subcavata MOTYKA, Usnea sp., Ramalina sp., Cladina confusa (SANT.) FOLMM. & AHTI, Dirinaria aspera HÄSÄNEN, and Parmotrema lichexanthonicum ELIASARO & ADLER were evaluated against UACC-62 and B16-F10 melanoma cells and 3T3 normal cells. Sulforhodamine B assay revealed significant cytotoxic activity in protocetraric, divaricatic, and perlatolic acids on UACC-62 cells (50% growth inhibitory concentration (GI(50)) 0.52, 2.7, and 3.3 µg/mL, respectively). Divaricatic and perlatolic acids proved the most active on B16-F10 cells (GI(50) 4.4, 18.0 µg/mL, respectively) and the most cytotoxic to 3T3 normal cells. Diffractaic, usnic, norstictic, and psoromic acids were cytotoxic to UACC-62 cells in the 24.7 to 36.6 µg/mL range, as were protocetraric and diffractaic acids to B16-F10 cells (GI(50) 24.0, 25.4 µg/mL, respectively). Protocetraric acid was highly selective (selectivity index (SI*) 93.3) against UACC-62 cells, followed by norstictic, perlatolic, psoromic, and divaricatic acids, while norstictic and divaricatic acids were more selective against B16-F10 cells. The high SI* value obtained for protocetraric acid on UACC-62 cells makes it a potential candidate for the study of melanomas in experimental models. Chemometric analysis was performed to evaluate the general behavior of the compounds against the cell lines tested. PMID:23207680

  5. 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.

  6. Cancer cell spheroids as a model to evaluate chemotherapy protocols

    OpenAIRE

    Perche, Federico; Torchilin, Vladimir P.

    2012-01-01

    To determine whether the spheroid culture can be used to evaluate drug efficacy, we have evaluated the toxicity of free or carrier-associated doxorubicin as a single drug or in combination with other antineoplastic agents using the spheroid cultures of drug-resistant cancer cells. Paclitaxel, cisplatin, dexamethasone, mitoxantrone, sclareol or methotrexate were used in combination with doxorubicin. The effect of the treatment protocols on free, micellar and liposomal doxorubicin accumulation ...

  7. 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

  8. 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

  9. In vitro evaluation of the interactions between human corneal endothelial cells and extracellular matrix proteins.

    Science.gov (United States)

    Choi, Jin San; Kim, Eun Young; Kim, Min Jeong; Giegengack, Matthew; Khan, Faraaz A; Khang, Gilson; Soker, Shay

    2013-02-01

    The corneal endothelium is the innermost cell layer of the cornea and rests on Descemet's membrane consisting of various extracellular matrix (ECM) proteins which can directly affect the cellular behaviors such as cell adhesion, proliferation, polarity, morphogenesis and function. The objective of this study was to investigate the interactions between the ECM environment and human corneal endothelial cells (HCECs), with the ultimate goal to improve cell proliferation and function in vitro. To evaluate the interaction of HCECs with ECM proteins, cells were seeded on ECM-coated tissue culture dishes, including collagen type I (COL I), collagen type IV (COL IV), fibronectin (FN), FNC coating mix (FNC) and laminin (LM). Cell adhesion and proliferation of HCECs on each substratum and expression of CEC markers were studied. The results showed that HCECs plated on the COL I, COL IV, FN and FNC-coated plates had enhanced cell adhesion initially; the number for COL I, COL IV, FN and FNC was significantly higher than the control (P < 0.05). In addition, cells grown on ECM protein-coated dishes showed more compact cellular morphology and CEC marker expression compared to cells seeded on uncoated dishes. Collectively, our results suggest that an adequate ECM protein combination can provide a long-term culture environment for HCECs for corneal endothelium transplantation.

  10. 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.

  11. Evaluation of cell death after treatment with extracorporeal photopheresis.

    Science.gov (United States)

    Daniele, Nicola; Del Proposto, Gianpaolo; Cerrone, Paola; Sinopoli, Silvia; Sansone, Lucia; Gadaleta, Deborah Ilaria; Lanti, Alessandro; Ferraro, Angelo Salvatore; Spurio, Stefano; Scerpa, Maria Cristina; Zinno, Francesco; Adorno, Gaspare; Isacchi, Giancarlo

    2012-02-01

    The aim of our study is to assess the mortality of leukocytes during extracorporeal photopheresis. Sixty-three photopheresis performed on 13 patients affected by chronic GvHD were evaluated. Samples were analyzed using a FACSCalibur flow cytometer. Apoptosis and necrosis of limphomononuclear cells dramatically increased after the apheretic procedure. We found a further increase of apoptotic and necrotic limphomononuclear cells after treatment with 8-MOP and UVA (p≤0.05). Our data suggested that the immunomodulatory effects of extracorporeal photopheresis, triggered by circulating apoptotic or necrotic cells, could play an important role in the treatment of GvHD with this procedure.

  12. 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.

  13. 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.

  14. In vitro Th1 and Th2 cell polarization is severely influenced by the initial ratio of naïve and memory CD4+ T cells

    DEFF Research Database (Denmark)

    Blom, Lars; Poulsen, Lars K.

    2013-01-01

    by even small percentages (99% naïve CD4+ T cells resulted in better Th1 and Th2 polarization with significant reduced fractions of IL-4+ and IFN-γ+ CD4+ T cells, respectively. Moreover, the Th2 primed >99% naïve CD4+ T cells showed significantly higher ratio of IL-4+:IFN-γ+ (>4 fold) and GATA-3:+T......-bet+ (>3 fold) CD4+ T cells when compared with the standard purified >90-95% naïve CD4+ T cells primed under the same culture conditions. This suggests immunomagnetic bead separation, a low cost and easy available technique, with few modifications to the manufacturer's protocol as an attractive alternative...... for laboratories not having a cell sorter. Taken together, we report that it is essential to use rigorously purified (>99%) naïve CD4+ T cells for optimal initial in vitro Th1 and Th2 priming....

  15. Initial stem cell adhesion on porous silicon surface: molecular architecture of actin cytoskeleton and filopodial growth

    Science.gov (United States)

    Collart-Dutilleul, Pierre-Yves; Panayotov, Ivan; Secret, Emilie; Cunin, Frédérique; Gergely, Csilla; Cuisinier, Frédéric; Martin, Marta

    2014-10-01

    The way cells explore their surrounding extracellular matrix (ECM) during development and migration is mediated by lamellipodia at their leading edge, acting as an actual motor pulling the cell forward. Lamellipodia are the primary area within the cell of actin microfilaments (filopodia) formation. In this work, we report on the use of porous silicon (pSi) scaffolds to mimic the ECM of mesenchymal stem cells from the dental pulp (DPSC) and breast cancer (MCF-7) cells. Our atomic force microscopy (AFM), fluorescence microscopy, and scanning electron microscopy (SEM) results show that pSi promoted the appearance of lateral filopodia protruding from the DPSC cell body and not only in the lamellipodia area. The formation of elongated lateral actin filaments suggests that pores provided the necessary anchorage points for protrusion growth. Although MCF-7 cells displayed a lower presence of organized actin network on both pSi and nonporous silicon, pSi stimulated the formation of extended cell protrusions.

  16. 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

    growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8......) 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....... 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....

  17. 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...... are 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...

  18. 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

    are 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......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...... 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...

  19. Productivity through weaning of nine breeds of cattle under varying feed availabilities: I. Initial evaluation.

    Science.gov (United States)

    Jenkins, T G; Ferrell, C L

    1994-11-01

    The effect of varying dry matter availability on the conversion of dry matter resources to weight of calf at weaning was evaluated for nine breeds of cattle; Angus, Braunvieh, Charolais, Gelbvieh, Hereford, Limousin, Red Poll, Pinzgauer, and Simmental were recorded for 5 yr. Within each breed, four cows were assigned to each of four feeding levels of dry matter intake: 58, 76, 93, or 111 g of DM/wt75. Cows remained on their assigned diet regimen throughout the study. Individual cow consumption, daily feed allowance adjusted for refusal, was recorded weekly. Production information included birth and weaning weight of the progeny, calving rate, and cow weights and condition scores. Cows were exposed to bulls of the same breed for 90 d. Reasons for cow replacement included failure to conceive in two successive years, injury, Caesarean section, chronic illness, and death. Response to dry matter intake (DMI) was curvilinear and differed among breeds (P .20). Red Poll exhibited more effective conversion at DMI less than 4,000 kg/yr, but breeds with greater genetic potential for growth and(or) milk production (Gelbvieh, Charolais, Braunvieh, Simmental, Pinzgauer, and Limousin) were more efficient at DMI greater than 6,000 kg/yr. Ranking for biological production efficiency (weight of calf weaned-cow exposed-1.kg DMI of cow-1) through weaning among breeds of cattle varied with dry matter intake.

  20. 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.

  1. 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…

  2. 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.

  3. 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

  4. 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

  5. Initial Evaluation of Processing Methods for an Epsilon Metal Waste Form

    Energy Technology Data Exchange (ETDEWEB)

    Crum, Jarrod V.; Strachan, Denis M.; Zumhoff, Mac R.

    2012-06-11

    expected to have a high melting point as well, perhaps exceeding 1500 C. The purpose of the work reported here is to find a potential commercial process with which {var_epsilon}-metal plus other components of UDS can be consolidated into a solid with minimum surface area and high strength Here, we report the results from the preliminary evaluation of spark-plasma sintering (SPS), hot-isostatic pressing (HIP), and microwave sintering (MS). Since bulk {var_epsilon}-metal is not available and companies could not handle radioactive materials, we prepared mixtures of the five individual metal powders (Mo, Ru, Rh, Pd, and Re) and baddeleyite (ZrO{sub 2}) to send the vendors of SPS, HIP, and MS. The processed samples were then evaluated at the Pacific Northwest National Laboratory (PNNL) for bulk density and phase assemblage with X-ray diffraction (XRD) and phase composition with scanning electron microscopy (SEM). Physical strength was evaluated qualitatively. Results of these scoping tests showed that fully dense cermet (ceramic-metal composite) materials with up to 35 mass% of ZrO{sub 2} were produced with SPS and HIP. Bulk density of the SPS samples ranged from 87 to 98% of theoretical density, while HIP samples ranged from 96 to 100% of theoretical density. Microwave sintered samples containing ZrO{sub 2} had low densities of 55 to 60% of theoretical density. Structurally, the cermet samples showed that the individual metals alloyed in to {var_epsilon}-phase - hexagonal-close-packed (HCP) alloy (4-95 mass %), the {alpha}-phase - face-centered-cubic (FCC) alloy structure (3-86 mass %), while ZrO{sub 2} remained in the monoclinic structure of baddeleyite. Elementally, the samples appeared to have nearly uniform composition, but with some areas rich in Mo and Re, the two components with the highest melting points. The homogeneity in distribution of the elements in the alloy is significantly improved in the presence of ZrO{sub 2}. However, ZrO{sub 2} does not appear to react

  6. 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.)

  7. 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…

  8. T-cell mean telomere lengths changes in treatment naïve HIV-infected patients randomized to G-CSF or placebo simultaneously with initiation of HAART

    DEFF Research Database (Denmark)

    Aladdin, H; Von Essen, M; Schjerling, P;

    2001-01-01

    of the mean CD8+ T-cell TRF length. However, G-CSF given simultaneously with HAART induces an inhibition of the expected lengthening in mean TRF length. These results do therefore not support the use of adjuvant G-CSF treatment simultaneously when initiating HAART and should further be evaluated before use...

  9. 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.

  10. 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

  11. Laser-SQUID microscope for noncontact evaluation of solar cell

    Energy Technology Data Exchange (ETDEWEB)

    Nakatani, Y., E-mail: nakatani@sup.ee.es.osaka-u.ac.jp [Osaka University, 1-3, Machikaneyama, Toyonaka, Osaka 560-8531 (Japan); Hayashi, T. [Sendai National College of Technology, 4-16-1, Ayashityuou, Aoba-ku, Sendai, Miyagi 989-3128 (Japan); Itozaki, H. [Osaka University, 1-3, Machikaneyama, Toyonaka, Osaka 560-8531 (Japan)

    2011-11-15

    A polycrystalline solar cell was investigated by the laser-SQUID microscope without contact to the surface of the solar cell. The laser-SQUID microscope image of the solar cell was similar to the laser-beam-induced current image. The laser-SQUID microscope images varied when the needle and the SQUID were shifted in the x- and y-directions from the center of a laser spot. The laser-SQUID microscopy has the possibility of estimation of the photocurrent direction. A polycrystalline solar cell with several grains was investigated by the laser-SQUID (Superconducting QUantum Interference Device) microscope. The laser-SQUID microscopy detects the magnetic field generated by a photo-induced current. This technique enables nondestructive and noncontact evaluation of semiconductor samples. A needle made of high permeability material was used to transmit the magnetic field near the sample to the SQUID. The needle and the SQUID were shifted in the x- and y-directions from the center of a laser spot. The laser-SQUID microscope images varied with needle position. This indicated the possibility of current estimation using a laser-SQUID microscope. In this study the sample was also evaluated using Laser Beam Induced Current (LBIC) which is widely used for evaluation of the conversion efficiency distribution of solar cells. The laser-SQUID microscope image was compared with the LBIC image and was found to be similar. This result showed that laser-SQUID microscopy can be used for the electrical evaluation of solar cells without contact, and furthermore has the possibility of estimation of the photocurrent direction.

  12. Sox17 promotes cell cycle progression and inhibits TGF-beta/Smad3 signaling to initiate progenitor cell behavior in the respiratory epithelium.

    Directory of Open Access Journals (Sweden)

    Alexander W Lange

    Full Text Available The Sry-related high mobility group box transcription factor Sox17 is required for diverse developmental processes including endoderm formation, vascular development, and fetal hematopoietic stem cell maintenance. Expression of Sox17 in mature respiratory epithelial cells causes proliferation and lineage respecification, suggesting that Sox17 can alter adult lung progenitor cell fate. In this paper, we identify mechanisms by which Sox17 influences lung epithelial progenitor cell behavior and reprograms cell fate in the mature respiratory epithelium. Conditional expression of Sox17 in epithelial cells of the adult mouse lung demonstrated that cell cluster formation and respecification of alveolar progenitor cells toward proximal airway lineages were rapidly reversible processes. Prolonged expression of Sox17 caused the ectopic formation of bronchiolar-like structures with diverse respiratory epithelial cell characteristics in alveolar regions of lung. During initiation of progenitor cell behavior, Sox17 induced proliferation and increased the expression of the progenitor cell marker Sca-1 and genes involved in cell cycle progression. Notably, Sox17 enhanced cyclin D1 expression in vivo and activated cyclin D1 promoter activity in vitro. Sox17 decreased the expression of transforming growth factor-beta (TGF-beta-responsive cell cycle inhibitors in the adult mouse lung, including p15, p21, and p57, and inhibited TGF-beta1-mediated transcriptional responses in vitro. Further, Sox17 interacted with Smad3 and blocked Smad3 DNA binding and transcriptional activity. Together, these data show that a subset of mature respiratory epithelial cells retains remarkable phenotypic plasticity and that Sox17, a gene required for early endoderm formation, activates the cell cycle and reinitiates multipotent progenitor cell behavior in mature lung cells.

  13. 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.

  14. 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

  15. 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

  16. 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.)

  17. 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.)

  18. 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...

  19. 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...

  20. Telomere and telomerase in the initial stage of immortalization of esophageal epithelial cell

    Institute of Scientific and Technical Information of China (English)

    Zhong-Ying Shen; Li-Yan Xu; En-Min Li; Wei-Jia Cai; Min-Hua Chen; Jian Shen; Yi Zeng

    2002-01-01

    AIM: To search for the biomarker of cellular immortalization,the telomere length, telomerase activity and its subunits incultured epithelial cells of human fetal esophagus in theprocess of immortalization.METHODS: The transgenic cell line of human fetalesophageal epithelium (SHEE) was established with E6 E7genes of bt man papillomavirus (HPV) type 18 in ourlaboratory. Morphological phenotype of cultured SHEE cellsfrom the 6th to 30th passages, was examined by phasecontrast microscopy, the telomere length was assayed bySouthern blot method, and the activity of telomerase wasanalyzed by telomeric repeat amplification protocol (TRAP).Expressions of subunits of telomerase, hTR and hTERT,were assessed by RT-PCR. DNA content in cell cycle wasdetected by flow cytometry. The cell apoptosis wasexamined by electron microscopy (EM) and TUNEL label.RESULTS: SHEE cells from the 6 th to 10 th passagesshowed cellular proliferation with a good differentiation.From the 12 th to the 16 th passages, many senescent andapoptotic cells appeared, and the telomere length sharplyshortened from 23 kb to 17 kb without expression of hTERTand telornerase activity. At the 20 th passage, SHEE cellsovercame the senescence and apoptosis and restored theirproliferative activity with expression of telomerase andhTERT at low levels, but the telomere length shortenedcontinuously to the lowest of 3 kb. After the 30 th passagecells proliferation was restored by increment of cells at S andG2M phase in the cell cycle end telomerase activity expressedat high levels and with maintenance of telomere length.CONCLUSION: At the early stage of SHEE cells, telomeresare shortened without expression of telomerase and hTERTcausing cellular senescence and cell death. From the 20 thto the 30 th passages, the activation of telomerase andmaintenance of telomere length show a progressive processfor immortalization of esophageal epithelial cells. Theexpression of telomerase may constitute a biomarker fordetection of

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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...

  7. Initiation of V(D)J recombination in a cell-free system

    NARCIS (Netherlands)

    D.C. van Gent (Dik); J.F. McBlane; D.A. Ramsden; M.J. Sadokfsky; J.E. Hesse (Joanne); M. Gellert

    1995-01-01

    textabstractCells performing V(D)J recombination make specific cuts in DNA at recombination signal sequences. Here, we show that nuclear extracts of pre-B cell lines carry out this specific cleavage. The products of cleavage are the same as found previously in thymocytes: full-leng

  8. 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.

  9. Lipid raft regulates the initial spreading of melanoma A375 cells by modulating β1 integrin clustering.

    Science.gov (United States)

    Wang, Ruifei; Bi, Jiajia; Ampah, Khamal Kwesi; Zhang, Chunmei; Li, Ziyi; Jiao, Yang; Wang, Xiaoru; Ba, Xueqing; Zeng, Xianlu

    2013-08-01

    Cell adhesion and spreading require integrins-mediated cell-extracellular matrix interaction. Integrins function through binding to extracellular matrix and subsequent clustering to initiate focal adhesion formation and actin cytoskeleton rearrangement. Lipid raft, a liquid ordered plasma membrane microdomain, has been reported to play major roles in membrane motility by regulating cell surface receptor function. Here, we identified that lipid raft integrity was required for β1 integrin-mediated initial spreading of melanoma A375 cells on fibronectin. We found that lipid raft disruption with methyl-β-cyclodextrin led to the inability of focal adhesion formation and actin cytoskeleton rearrangement by preventing β1 integrin clustering. Furthermore, we explored the possible mechanism by which lipid raft regulates β1 integrin clustering and demonstrated that intact lipid raft could recruit and modify some adaptor proteins, such as talin, α-actinin, vinculin, paxillin and FAK. Lipid raft could regulate the location of these proteins in lipid raft fractions and facilitate their binding to β1 integrin, which may be crucial for β1 integrin clustering. We also showed that lipid raft disruption impaired A375 cell migration in both transwell and wound healing models. Together, these findings provide a new insight for the relationship between lipid raft and the regulation of integrins.

  10. The initiator methionine tRNA drives cell migration and invasion leading to increased metastatic potential in melanoma

    Science.gov (United States)

    Birch, Joanna; Clarke, Cassie J.; Campbell, Andrew D.; Campbell, Kirsteen; Mitchell, Louise; Liko, Dritan; Kalna, Gabriela; Strathdee, Douglas; Sansom, Owen J.; Neilson, Matthew; Blyth, Karen

    2016-01-01

    ABSTRACT The cell's repertoire of transfer RNAs (tRNAs) has been linked to cancer. Recently, the level of the initiator methionine tRNA (tRNAiMet) in stromal fibroblasts has been shown to influence extracellular matrix (ECM) secretion to drive tumour growth and angiogenesis. Here we show that increased tRNAiMet within cancer cells does not influence tumour growth, but drives cell migration and invasion via a mechanism that is independent from ECM synthesis and dependent on α5β1 integrin and levels of the translation initiation ternary complex. In vivo and ex vivo migration (but not proliferation) of melanoblasts is significantly enhanced in transgenic mice which express additional copies of the tRNAiMet gene. We show that increased tRNAiMet in melanoma drives migratory, invasive behaviour and metastatic potential without affecting cell proliferation and primary tumour growth, and that expression of RNA polymerase III-associated genes (which drive tRNA expression) are elevated in metastases by comparison with primary tumours. Thus, specific alterations to the cancer cell tRNA repertoire drive a migration/invasion programme that may lead to metastasis. PMID:27543055

  11. Test and Approval Center for Fuel Cell and Hydrogen Technologies: Phase I. Initiation

    DEFF Research Database (Denmark)

    electricity - can be converted to power and heat. The increased use of hydrogen will decrease oil dependency, which is foreseen to have profound economic as well as political impacts. Fuel cell and hydrogen technologies play an important role in future sustainable energy system scenarios, often in combination......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 pollutants - for example no toxic NOx at all - than conventional plants do. Fuel cells can operate on fossil...

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. Initial embryology and pluripotent stem cells in the pig--The quest for establishing the pig as a model for cell therapy.

    Science.gov (United States)

    Secher, Jan O; Callesen, Henrik; Freude, Kristine K; Hyttel, Poul

    2016-01-01

    The quest for porcine pluripotent stem cells (PSCs) was initiated in the early 90s. Initially, it was the intention to benefit from these cells for production of genetically modified pigs using homologous recombination followed by derivation of chimeric offspring; a technology that has been used to produce genetically modified mice since the mid-80s. However, no convincing reports on the generation of bona fide porcine embryonic stem cells or embryonic germ cells resulted from these activities, and with the advent of somatic cell nuclear transfer during the late 90s, alternative methods for creating genetically modified pigs emerged. Over the past years, renewed interest in porcine PSCs has sparked activities in deriving in particular porcine induced pluripotent stem cells to develop the pig as a faithful model for studying the potentials and risks associated with induced pluripotent stem cell-based human therapy. Here, we review the recent data on establishment of porcine PSCs and the differences in embryonic development between pig and mouse, which may be underlying factors for the continuing challenge to culture and maintain porcine PSCs.

  18. 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...

  19. Cell size at S phase initiation: an emergent property of the G1/S network.

    Directory of Open Access Journals (Sweden)

    Matteo Barberis

    2007-04-01

    Full Text Available The eukaryotic cell cycle is the repeated sequence of events that enable the division of a cell into two daughter cells. It is divided into four phases: G1, S, G2, and M. Passage through the cell cycle is strictly regulated by a molecular interaction network, which involves the periodic synthesis and destruction of cyclins that bind and activate cyclin-dependent kinases that are present in nonlimiting amounts. Cyclin-dependent kinase inhibitors contribute to cell cycle control. Budding yeast is an established model organism for cell cycle studies, and several mathematical models have been proposed for its cell cycle. An area of major relevance in cell cycle control is the G1 to S transition. In any given growth condition, it is characterized by the requirement of a specific, critical cell size, PS, to enter S phase. The molecular basis of this control is still under discussion. The authors report a mathematical model of the G1 to S network that newly takes into account nucleo/cytoplasmic localization, the role of the cyclin-dependent kinase Sic1 in facilitating nuclear import of its cognate Cdk1-Clb5, Whi5 control, and carbon source regulation of Sic1 and Sic1-containing complexes. The model was implemented by a set of ordinary differential equations that describe the temporal change of the concentration of the involved proteins and protein complexes. The model was tested by simulation in several genetic and nutritional setups and was found to be neatly consistent with experimental data. To estimate PS, the authors developed a hybrid model including a probabilistic component for firing of DNA replication origins. Sensitivity analysis of PS provides a novel relevant conclusion: PS is an emergent property of the G1 to S network that strongly depends on growth rate.

  20. 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. .

  1. CK2 phosphorylation of eukaryotic translation initiation factor 5 potentiates cell cycle progression

    OpenAIRE

    Homma, Miwako Kato; Wada, Ikuo; Suzuki, Toshiyuki; Yamaki, Junko; Krebs, Edwin G.; Homma, Yoshimi

    2005-01-01

    Casein kinase 2 (CK2) is a ubiquitous eukaryotic Ser/Thr protein kinase that plays an important role in cell cycle progression. Although its function in this process remains unclear, it is known to be required for the G1 and G2/M phase transitions in yeast. Here, we show that CK2 activity changes notably during cell cycle progression and is increased within 3 h of serum stimulation of quiescent cells. During the time period in which it exhibits high enzymatic activity, CK2 associates with and...

  2. 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.

  3. Ectopic bone formation in rat marrow stromal cell/titanium fiber mesh scaffold constructs: effect of initial cell phenotype.

    NARCIS (Netherlands)

    Holtorf, H.L.; Jansen, J.A.; Mikos, A.G.

    2005-01-01

    Titanium fiber mesh scaffolds have been shown to be a suitable material for culture of primary marrow stromal cells in an effort to create tissue engineered constructs for bone tissue replacement. In native bone tissue, these cells are known to attach to extracellular matrix molecules via integrin r

  4. 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.

  5. 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.

  6. The rise of developmental genetics - a historical account of the fusion of embryology and cell biology with human genetics and the emergence of the Stem Cell Initiative.

    Science.gov (United States)

    Kidson, S H; Ballo, R; Greenberg, L J

    2016-05-25

    Genetics and cell biology are very prominent areas of biological research with rapid advances being driven by a flood of theoretical, technological and informational knowledge. Big biology and small biology continue to feed off each other. In this paper, we provide a brief overview of the productive interactions that have taken place between human geneticists and cell biologists at UCT, and credit is given to the enabling environment created led by Prof. Peter Beighton. The growth of new disciplines and disciplinary mergers that have swept away division of the past to make new exciting syntheses are discussed. We show how our joint research has benefitted from worldwide advances in developmental genetics, cloning and stem cell technologies, genomics, bioinformatics and imaging. We conclude by describing the role of the UCT Stem Cell Initiative and show how we are using induced pluripotent cells to carry out disease-in-the- dish studies on retinal degeneration and fibrosis.

  7. Simultaneous knockdown of p18INK4C, p27Kipl and MAD1 via RNA interference results in the expansion of long-term culture-initiating cells of murine bone mar-row cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Yan-Yi Wang; Yong Yang; Qingyong Chen; Jianping Yu; Yongzhong Hou; Lizhen Han; Jun He; Demin Jiao; Huihui Yu

    2008-01-01

    A combination of extrinsic hematopoietic growth regulators,such as stem cell factor (SCF), interleukin (IL)-3 and IL-6,can induce division of quiescent hematopoietic stem cells (HSCs), but it usually impairs HSCs' serf-renewal ability.However,intrinsic negative cell cycle regulators,such as p18INK4C(p18),p27Kip1(p27)and MAD1,can regulate the self-renewal of HSCs.It is unknown whether the removal of some extrinsic regulators and the knockdown of intrinsic negative cell cycle regulators via RNA interference (RNAi)induce ex vivo expansion of the HSCs.To address this question,a lentiviral vector-based RNAitool was developed to produce two copies of small RNA that target multiple genes to knock-down the intrinsic negative cell cycle regulators p18,p27 and MAD1.Colony-forming cells,long-term culture-initiating cell(LTC-IC)and engraftment assays were used to evaluate the effects of extrinsic and intrinsic regulators.Results showed that the medium with only SCF,but without IL-3 and IL-6,could maintain the sca-1+c-kit+bone marrow cells with high LTC-IC frequency and low cell division. However,whenthe sca-1+c-kit+bone marrow cells were cultured in a medium with only SCF and simultaneously knocked down the expression of p18,p27and MAD1 via the lentiviral vector-based RNAI,the cells exhibited both high LTC-IC frequency and high cell division,though engraftment failed.Thus,the simultaneous lnockdown of p18,p27and MAD1 with a medium of only SCF can induce LTC-IC expansion despite the loss of engraftment ability.

  8. Characterization and propagation of tumor initiating cells derived from colorectal liver metastases: trials, tribulations and a cautionary note.

    Directory of Open Access Journals (Sweden)

    Mark I James

    Full Text Available Tumor initiating cells (TIC are increasingly being put forward as a potential target for intervention within colorectal cancer. Whilst characterisation and outgrowth of these cells has been extensively undertaken in primary colorectal cancers, few data are available describing characteristics within the metastatic setting. Tissue was obtained from patients undergoing surgical resection for colorectal liver metastases, and processed into single cell suspension for assessment. Tumor initiating cells from liver metastases were characterised using combinations of EPCAM, Aldehyde dehydrogenase activity, CD133 and CD26. CD133 expression was significantly lower in patients who had received chemotherapy, but this was accounted for by a decrease observed in the male patient cohort only. ALDHhigh populations were rare (0.4 and 0.3% for EPCAM+/ALDHhigh/CD133- and EPCAM+/ALDHhigh/CD133+ populations respectively and below the limits of detection in 28% of samples. Spheroid outgrowth of metastatic tumor cells across all samples could not be readily achieved using standard spheroid-formation techniques, thus requiring further method validation to reliably propagate cells from the majority of tissues. Spheroid formation was not enhanced using additional growth factors or fibroblast co-culture, but once cells were passaged through NOD-SCID mice, spheroid formation was observed in 82% samples, accompanied by a significant increase in CD26. Order of spheroid forming ability was ALDHhigh>CD133>CD26. Samples sorted by these markers each had the ability to reform ALDHhigh, CD133 and CD26 positive populations to a similar extent, suggestive of a high degree of plasticity for each population. Ex vivo TIC models are increasingly being utilised to assess efficacy of therapeutic interventions. It is therefore essential that such investigations use well-characterised models that are able to sustain TIC populations across a large patient cohort in order that the inherent

  9. 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.

  10. 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. ...

  11. 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...

  12. 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...

  13. 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.

  14. Evaluation of the MOST (Making the Most of Out-of-School Time) Initiative: Final Report. Summary of Findings. Discussion Paper.

    Science.gov (United States)

    Halpern, Robert; Spielberger, Julie; Robb, Sylvan

    The University of Chicago's Chapin Hall Center for Children conducted an evaluation of the first phase (1995-1998) of the MOST (Making the Most of Out-of-School Time) Initiative of the Wallace-Reader's Digest Funds. The objectives of this initiative were to contribute to the supply, accessibility, affordability, and quality of after-school…

  15. 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

  16. 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

  17. Cocultivation of umbilical cord blood CD34+ cells with retro-transduced hMSCs leads to effective amplification of long-term culture-initiating cells

    Institute of Scientific and Technical Information of China (English)

    Chun-Gang Xie; Jin-Fu Wang; Ying Xiang; Li-Yan Qiu; Bing-Bing Jia; Li-Juan Wang; Guo-Zhong Wang; Guo-Ping Huang

    2006-01-01

    AIM: To establish a novel coculture system for ex vivo expansion of umbilical cord blood(UCB) hematopoietic progenitors using thrombopoietin (TPO)/Flt-3 ligand(FL)-transduced human marrow-derived mesenchymal stem cells (tfhMSCs) as feeder.METHODS: UCB CD34+ cells were isolated and cultured using four culture systems in serum-containing or serumfree medium. Suitable aliquots of cultured cells were used to monitor cell production, clonogenic activity,and long-term culture-initiating culture (LTC-IC) output.Finally, the severe-combined immunodeficient (SCID)mouse-repopulating cell (SRC) assay was performed to confirm ability of the cultured cells to reconstitute longterm hematopoiesis.RESULTS: There were no significant differences in the number of total nucleated cells among different culture systems in serum-containing medium during 21-d culture. However, on d 14, the outputs of CD34+ cells,CFU-C and CFU-GEMM in tfhMSCs coculture system were significantly enhanced. LTC-IC assay demonstrated that the tfhMSCs coculture system had the most powerful activity. The severe-combined immunodeficient (SCID)mouse repopulating cell (SRC) assay confirmed extensive ability of the expanded cells to reconstitute long-term hematopoiesis. Furthermore, PCR analysis demonstrated the presence of human hematopoietic cells in the bone marrow and peripheral blood cells of NOD/SCID mice.CONCLUSION: The TPO/FL-transduced hMSCs, in combination with additive cytokines, can effectively expand hematopoietic progenitors from UCB in vitro and the tfhMSCs coculture system may be a suitable system for ex vivo manipulation of primitive progenitor cells under contact culture conditions.

  18. 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.

  19. Distinct Functions of Different scl Isoforms in Zebrafish Definitive Hematopoietic Stem Cell Initiation and Maintenance

    Science.gov (United States)

    Lan, Yahui

    2011-07-01

    The establishment of entire blood system relies on the multi-potent hematopoietic stem cells (HSCs), thus identifying the molecular mechanism in HSC generation is of importance for not only complementing the fundamental knowledge in stem cell biology, but also providing insights to the regenerative therapies. Recent researches have documented the formation of nascent HSCs through a direct transition from ventral aortic endothelium, named as endothelial hematopoietic transition (EHT) process. However, the precise genetic program engaged in this process remains largely elusive. The transcription factor scl plays pivotal and conserved roles in embryonic and adult hematopoiesis from teleosts to mammals. Our lab have previously identified a new truncated scl isoform, scl-beta, which is indispensible for the specification of HSCs in the ventral wall of dorsal aorta (VDA), the zebrafish equivalent of mammalian fetal hematopoietic organ. Here we observe that, by combining time-lapse confocal imaging of transgenic zebrafish and genetic epistasis analysis, scl-beta is expressed in a subset of ventral aortic endothelial cells and critical for their forthcoming transformation to hemogenic endothelium; in contrast, runx1 is required downstream to govern the successful egress of the hemogenic endothelial cells to become naive HSCs. In addition, the traditional known full-length scl-alpha isoform is firstly evidenced to be required for the maintenance or survival of newly formed HSCs in VDA. Collectively our data has established the genetic hierarchy controlling discrete steps in the consecutive process of HSC formation from endothelial cells and further development in VDA.

  20. [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

  1. 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.

  2. 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

  3. 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.

  4. It’s All About Change: The Antigen-driven Initiation of B-Cell Receptor Signaling

    Science.gov (United States)

    Liu, Wanli; Sohn, Hae Won; Tolar, Pavel; Pierce, Susan K.

    2010-01-01

    B-cell responses are initiated by the binding of foreign antigens to the clonally distributed B-cell receptors (BCRs) resulting in the triggering of signaling cascades that activate a variety of genes associated with B-cell activation. Although we now understand the molecular nature of the signaling pathways in considerable detail what remains only poorly understood are the mechanisms by which the information that antigen has bound to the BCR ectodomain is transduced across the B-cell membrane to the BCR cytoplasmic domains to trigger signaling. To a large part this gap in knowledge is because of the paucity of techniques to temporally and spatially resolve changes in the behavior of the BCR that occur within several seconds of antigen binding. With the advent of new live-cell imaging technologies we are gaining our first clear views of the events that lead up to the triggering of BCR signaling cascades. These events may provide potential new targets for therapeutic intervention in disease involving hyper or chronic activation of B cells. PMID:20591989

  5. Tetrandrine, a Compound Common in Chinese Traditional Medicine, Preferentially Kills Breast Cancer Tumor Initiating Cells (TICs In Vitro

    Directory of Open Access Journals (Sweden)

    Jessica Li

    2011-05-01

    Full Text Available Tetrandrine is a bisbenzylisoquinoline alkaloid found in Stephania tetrandra, a Chinese medicine commonly used as an anti-inflammatory. It has extensive pharmacological activity, including positive ion channel blockade and inhibition of multiple drug resistance proteins. These activities are very similar to that of salinomycin, a known drug targeting breast cancer initiation cells (TICs. Herein, we tested tetrandrine targeting of breast cancer TICs. SUM-149, an inflammatory breast cancer cell line and SUM-159, a non-inflammatory metaplastic breast cancer cell line were used in these studies. In proliferation assays using 3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium (MTS, we found that the IC50 for inhibition of proliferation is 15.3 ± 4.1 µM for SUM-149 and 24.3 ± 2.1 µM for SUM-159 cells. Tetrandrine also inhibited mammosphere formation, a surrogate for breast cancer TICs growth in vitro with IC50 around 1 µM for SUM-149 and around 2 µM for SUM-159 cells. Tetrandrine has similar effects on the mammosphere formation from cells isolated from fresh patient sample. Moreover, tetrandrine decreases the aldehyde dehydrogenase (ALDH positive population in SUM-159 by 45% ± 5.45% P = 0.005. In summary, tetrandrine demonstrates significant efficacy against in vitro surrogates for inflammatory and aggressive breast cancer TICs.

  6. Oct4 mediates tumor initiating properties in oral squamous cell carcinomas through the regulation of epithelial-mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    Lo-Lin Tsai

    Full Text Available BACKGROUND: Overexpression of Oct4, an important transcription factor of embryonic stem cells (ESC, has been reported in several cancers. The aim of this study was to determine the emerging role of Oct4 in oral squamous cell carcinoma (OSCC both in vitro and in vivo. METHODOLOGY/PRINCIPAL FINDING: Tumourigenic activity and molecular mechanisms of Oct4 overexpression or knockdown by lentiviral infection in OSCC was investigated in vitro and in vivo. Initially, we demonstrated that Oct4 expression was increased in OSCC cell lines as compared to a normal oral epithelial cell line SG. Overexpression of Oct4 was demonstrated to enhance cell proliferation, invasiveness, anchorage-independent growth and xenotransplantation tumourigenicity. These findings were coupled with epithelial-mesenchymal transition (EMT transformation in OSCCs. In contrast, the silence of Oct4 significantly blocked the xenograft tumorigenesis of OSCC-derived cancer stem cells (OSCC-CSCs and significantly improved the recipient survival. Clinically, the level of Oct4 expression was higher in recurrent and metastatic OSCC specimens but lower in primary OSCC specimens. CONCLUSION/SIGNIFICANCE: Our results suggest that Oct4-mediated tumorigenecity is associated with the regulation of EMT. Oct4 might be a therapeutic target for OSCC.

  7. An energy efficiency evaluation of architectural and construction solutions of an initial design stage in Autodesk REVIT Architecture

    Directory of Open Access Journals (Sweden)

    S.A. Bolotin

    2013-12-01

    Full Text Available The aim of this study was to develop evaluation criteria for the various options of the project on the basis of information of the initial design phase. Objective of the study was to develop a methodology for assessing the architectural decisions on the basis of the building information model (BIM, formed by the program Autodesk Revit Architecture. The study suggested new compact solutions for evaluating insolation on vertical and horizontal surfaces and simplified algorithm for calculating the heat loss of the building, allowing the introduction of the relevant information in a program like Revit Architecture to simulate virtual water and energy balance at the early stages of design. Applying the final value tariffs for water and electricity supply of the area, you can get a virtual operating cash flow. For correct economic comparison of conceptual design options you should take into account time differences in costs and revenues by discounting. For rapid assessment of design solutions a model that allows you to simulate the scheduling of the facility necessary for the formation of the investment cash flow was developed. The proposed method can significantly improve the ability of the variant design incorporated into the program such as Revit Architecture.

  8. An Innovative Tool for Intraoperative Electron Beam Radiotherapy Simulation and Planning: Description and Initial Evaluation by Radiation Oncologists

    International Nuclear Information System (INIS)

    Purpose: Intraoperative electron beam radiation therapy (IOERT) involves a modified strategy of conventional radiation therapy and surgery. The lack of specific planning tools limits the spread of this technique. The purpose of the present study is to describe a new simulation and planning tool and its initial evaluation by clinical users. Methods and Materials: The tool works on a preoperative computed tomography scan. A physician contours regions to be treated and protected and simulates applicator positioning, calculating isodoses and the corresponding dose–volume histograms depending on the selected electron energy. Three radiation oncologists evaluated data from 15 IOERT patients, including different tumor locations. Segmentation masks, applicator positions, and treatment parameters were compared. Results: High parameter agreement was found in the following cases: three breast and three rectal cancer, retroperitoneal sarcoma, and rectal and ovary monotopic recurrences. All radiation oncologists performed similar segmentations of tumors and high-risk areas. The average applicator position difference was 1.2 ± 0.95 cm. The remaining cancer sites showed higher deviations because of differences in the criteria for segmenting high-risk areas (one rectal, one pancreas) and different surgical access simulated (two rectal, one Ewing sarcoma). Conclusions: The results show that this new tool can be used to simulate IOERT cases involving different anatomic locations, and that preplanning has to be carried out with specialized surgical input.

  9. Evaluation of a pharmacist intervention on patients initiating pharmacological treatment for depression: a randomized controlled superiority trial.

    Science.gov (United States)

    Rubio-Valera, Maria; March Pujol, Marian; Fernández, Ana; Peñarrubia-María, M Teresa; Travé, Pere; López Del Hoyo, Yolanda; Serrano-Blanco, Antoni

    2013-09-01

    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 were followed up at 6 months and evaluated three times (Baseline, and at 3 and 6 months). Outcome measurements included clinical severity of depression (PHQ-9), health-related quality of life (HRQOL) (Euroqol-5D) and satisfaction with pharmacy care. Adherence was continuously registered from the computerised pharmacy records. Non-adherence was defined as refilling less than 80% of doses or having a medication-free gap of more than 1 month. Patients in the intervention group were more likely to remain adherent at 3 and 6 months follow-up but the difference was not statistically significant. Patients in the intervention group showed greater statistically significant improvement in HRQOL compared with UC patients both in the main analysis and PP analyses. No statistically significant differences were observed in clinical symptoms or satisfaction with the pharmacy service. The results of our study indicate that a brief intervention in community pharmacies does not improve depressed patients' adherence or clinical symptoms. This intervention helped patients to improve their HRQOL, which is an overall measure of patient status. PMID:23219937

  10. An Innovative Tool for Intraoperative Electron Beam Radiotherapy Simulation and Planning: Description and Initial Evaluation by Radiation Oncologists

    Energy Technology Data Exchange (ETDEWEB)

    Pascau, Javier, E-mail: jpascau@mce.hggm.es [Unidad de Medicina y Cirugia Experimental, Hospital General Universitario Gregorio Maranon, Madrid (Spain); Departamento de Bioingenieria e Ingenieria Aeroespacial, Universidad Carlos III de Madrid, Madrid (Spain); Santos Miranda, Juan Antonio [Servicio de Oncologia Radioterapica, Hospital General Universitario Gregorio Maranon, Madrid (Spain); Facultad de Medicina, Universidad Complutense de Madrid, Madrid (Spain); Calvo, Felipe A. [Servicio de Oncologia Radioterapica, Hospital General Universitario Gregorio Maranon, Madrid (Spain); Facultad de Medicina, Universidad Complutense de Madrid, Madrid (Spain); Departamento de Oncologia, Hospital General Universitario Gregorio Maranon, Madrid (Spain); Bouche, Ana; Morillo, Virgina [Consorcio Hospitalario Provincial de Castellon, Castellon (Spain); Gonzalez-San Segundo, Carmen [Servicio de Oncologia Radioterapica, Hospital General Universitario Gregorio Maranon, Madrid (Spain); Facultad de Medicina, Universidad Complutense de Madrid, Madrid (Spain); Ferrer, Carlos; Lopez Tarjuelo, Juan [Consorcio Hospitalario Provincial de Castellon, Castellon (Spain); and others

    2012-06-01

    Purpose: Intraoperative electron beam radiation therapy (IOERT) involves a modified strategy of conventional radiation therapy and surgery. The lack of specific planning tools limits the spread of this technique. The purpose of the present study is to describe a new simulation and planning tool and its initial evaluation by clinical users. Methods and Materials: The tool works on a preoperative computed tomography scan. A physician contours regions to be treated and protected and simulates applicator positioning, calculating isodoses and the corresponding dose-volume histograms depending on the selected electron energy. Three radiation oncologists evaluated data from 15 IOERT patients, including different tumor locations. Segmentation masks, applicator positions, and treatment parameters were compared. Results: High parameter agreement was found in the following cases: three breast and three rectal cancer, retroperitoneal sarcoma, and rectal and ovary monotopic recurrences. All radiation oncologists performed similar segmentations of tumors and high-risk areas. The average applicator position difference was 1.2 {+-} 0.95 cm. The remaining cancer sites showed higher deviations because of differences in the criteria for segmenting high-risk areas (one rectal, one pancreas) and different surgical access simulated (two rectal, one Ewing sarcoma). Conclusions: The results show that this new tool can be used to simulate IOERT cases involving different anatomic locations, and that preplanning has to be carried out with specialized surgical input.

  11. Manufacture, integration and demonstration of polymer solar cells in a lamp for the Lighting Africa initiative

    DEFF Research Database (Denmark)

    Krebs, Frederik C; Damgaard Nielsen, Torben; Fyenbo, Jan;

    2010-01-01

    Semitransparent flexible polymer solar cells were manufactured in a full roll-to-roll process under ambient conditions. After encapsulation a silver based circuit was printed onto the back side of the polymer solar cell module followed by sheeting and application of discrete components and vias...... mm. A hole with a ring was punched in one corner to enable mechanical fixation or tying. The lamp has two states. In the charging state it has a completely flat outline and will charge the battery when illuminated from either side while the front side illumination is preferable. When used as a lamp...

  12. 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

  13. Initial evaluation of {sup 227}Th-p-benzyl-DOTA-rituximab for low-dose rate {alpha}-particle radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Dahle, Jostein [Department of Radiation Biology, Rikshospitalet-Radiumhospitalet HE, Montebello, 0310 Oslo (Norway)]. E-mail: jostein.dahle@labmed.uio.no; Borrebaek, Jorgen [Algeta ASA, Kjelsasveien 172 A, 0411 Oslo (Norway); Melhus, Katrine B. [Department of Radiation Biology, Rikshospitalet-Radiumhospitalet HE, Montebello, 0310 Oslo (Norway); Bruland, Oyvind S. [Department of Clinical Medicine, University of Oslo, 0316 Oslo (Norway); Department of Oncology, Rikshospitalet-Radiumhospitalet HE, Montebello, 0310 Oslo (Norway); Salberg, Gro [Algeta ASA, Kjelsasveien 172 A, 0411 Oslo (Norway); Olsen, Dag Rune [Department of Radiation Biology, Rikshospitalet-Radiumhospitalet HE, Montebello, 0310 Oslo (Norway); Larsen, Roy H. [Algeta ASA, Kjelsasveien 172 A, 0411 Oslo (Norway)

    2006-02-15

    Radioimmunotherapy has proven clinically effective in patients with non-Hodgkin's lymphoma. Radioimmunotherapy trials have so far been performed with {beta}-emitting isotopes. In contrast to {beta}-emitters, the shorter range and high linear energy transfer (LET) of {alpha} particles allow for more efficient and selective killing of individually targeted tumor cells. However, there are several obstacles to the use of {alpha}-particle immunotherapy, including problems with chelation chemistry and nontarget tissue toxicity. The {alpha}-emitting radioimmunoconjugate {sup 227}Th-DOTA-p-benzyl-rituximab is a new potential anti-lymphoma agent that might overcome some of these difficulties. The present study explores the immunoreactivity, in vivo stability and biodistribution, as well as the effect on in vitro cell growth, of this novel radioimmunoconjugate. To evaluate in vivo stability, uptake in balb/c mice of the {alpha}-particle-emitting nuclide {sup 227}Th alone, the chelated form, {sup 227}Th-p-nitrobenzyl-DOTA and the radioimmunoconjugate {sup 227}Th-DOTA-p-benzyl-rituximab was compared in a range of organs at increasing time points after injection. The immunoreactive fraction of {sup 227}Th-DOTA-p-benzyl-rituximab was 56-65%. During the 28 days after injection of radioimmunoconjugate only, very modest amounts of the {sup 227}Th had detached from DOTA-p-benzyl-rituximab, indicating a relevant stability in vivo. The half-life of {sup 227}Th-DOTA-p-benzyl-rituximab in blood was 7.4 days. Incubation of lymphoma cells with {sup 227}Th-DOTA-p-benzyl-rituximab resulted in a significant antigen-dependent inhibition of cell growth. The data presented here warrant further studies of {sup 227}Th-DOTA-p-benzyl-rituximab.

  14. Initial evaluation of 227Th-p-benzyl-DOTA-rituximab for low-dose rate α-particle radioimmunotherapy

    International Nuclear Information System (INIS)

    Radioimmunotherapy has proven clinically effective in patients with non-Hodgkin's lymphoma. Radioimmunotherapy trials have so far been performed with β-emitting isotopes. In contrast to β-emitters, the shorter range and high linear energy transfer (LET) of α particles allow for more efficient and selective killing of individually targeted tumor cells. However, there are several obstacles to the use of α-particle immunotherapy, including problems with chelation chemistry and nontarget tissue toxicity. The α-emitting radioimmunoconjugate 227Th-DOTA-p-benzyl-rituximab is a new potential anti-lymphoma agent that might overcome some of these difficulties. The present study explores the immunoreactivity, in vivo stability and biodistribution, as well as the effect on in vitro cell growth, of this novel radioimmunoconjugate. To evaluate in vivo stability, uptake in balb/c mice of the α-particle-emitting nuclide 227Th alone, the chelated form, 227Th-p-nitrobenzyl-DOTA and the radioimmunoconjugate 227Th-DOTA-p-benzyl-rituximab was compared in a range of organs at increasing time points after injection. The immunoreactive fraction of 227Th-DOTA-p-benzyl-rituximab was 56-65%. During the 28 days after injection of radioimmunoconjugate only, very modest amounts of the 227Th had detached from DOTA-p-benzyl-rituximab, indicating a relevant stability in vivo. The half-life of 227Th-DOTA-p-benzyl-rituximab in blood was 7.4 days. Incubation of lymphoma cells with 227Th-DOTA-p-benzyl-rituximab resulted in a significant antigen-dependent inhibition of cell growth. The data presented here warrant further studies of 227Th-DOTA-p-benzyl-rituximab

  15. Beyond White Blood Cell Monitoring : Screening in the Initial Phase of Clozapine Therapy

    NARCIS (Netherlands)

    Cohen, Dan; Bogers, Jan P. A. M.; van Dijk, Daniel; Bakker, Bert; Schulte, Peter F. J.

    2012-01-01

    Objective: Clozapine is the preferred option for treatment-resistant schizophrenia. However, since 1975, clozapine has been known to cause agranulocytosis. In the clozapine screening guidelines, white blood cell count is mandatory. In the past 20 years, after its reintroduction, 3 other serious side

  16. Cholangiocarcinoma Stem-like Cells Shapes Tumor-initiating Niche by Regulating Associated Macrophages

    DEFF Research Database (Denmark)

    Raggi, Chiara; Correnti, Margherita; Sica, Antonio;

    2016-01-01

    -SPHs were highly enriched for CSC, liver cancer and embryonic stem cell markers both at gene and protein levels. Next, FACS-analysis showed that in presence of CCA-SPH-CM, CD14+ expressed key macrophage (MØ) markers (CD68, CD115, HLA-DR, CD206) indicating that CCA-SPH- conditioned medium was a strong MØ...

  17. A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation

    DEFF Research Database (Denmark)

    Shih, Hung Ping; Kopp, Janel L; Sandhu, Manbir;

    2012-01-01

    differentiation necessitates subsequent Sox9 downregulation and evasion from Notch activity via cell-autonomous repression of Sox9 by Ngn3. If high Notch levels are maintained, endocrine progenitors retain Sox9 and undergo ductal fate conversion. Taken together, our findings establish a novel role for Notch in...

  18. Proton exchange fuel cell : the design, construction and evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Heinzen, M.R.; Simoes, G.C.; Da Silva, L. [Univ. do Vale do Itajai, Sao Jose, SC (Brazil). Lab. de Pesquisa em Energia; Fiori, M.A.; Paula, M.M.S. [Univ. do Extremo Sul Catarinense, Santa Catarina (Brazil). Lab. de Sintese de Complexos Multifuncionais; Benavides, R. [Centro de Investigacion en Quimica Aplicada, Coahuila (Mexico)

    2010-07-15

    Polymer electrolyte membrane fuel cells (PEMFC) convert the chemical energy stored in the fuel directly into electrical energy without intermediate steps. The PEMFC operates at a relatively low operating temperature making it a good choice for mobile applications, but a high power density is needed in order to decrease the total weight of the vehicles. This paper presented a simple methodology to construct a PEMFC-type fuel cell, with particular reference to the gaseous diffuser, cell structure, the fixing plate, mounting bracket, gas distribution plates, and the membrane electrode assembly (MEA). The geometric design and meshing of the PEMFC were also described. The electrode was made using graphite with flow-field geometry. The PEMFC was tested for 100 hour of continuous work, during which time the current and voltage produced were monitored in order to evaluate the performance of the PEMFC. The materials used in the preparation of the fuel cell proved to be suitable. There was no loss of efficiency during the tests. The most relevant aspects affecting the PEMFC design were examined in an effort to optimize the performance of the cell. 13 refs., 6 figs.

  19. γδ T cells recognize a microbial encoded B cell antigen to initiate a rapid antigen specific Interleukin 17 response

    Science.gov (United States)

    Zeng, Xun; Wei, Yu-ling; Huang, Jun; Newell, Evan W.; Yu, Hongxiang; Kidd, Brian A.; Kuhns, Michael S.; Waters, Ray W.; Davis, Mark M.; Weaver, Casey T.; Chien, Yueh-hsiu

    2012-01-01

    Summary γδ T cells contribute uniquely to host immune defense. However, how they function remains an enigma. Although it is unclear what most γδ T cells recognize, common dogma asserts that they recognize self-antigens. While they are the major initial Interleukin-17 (IL-17) producers in infections, it is unclear what is required to trigger these cells to act. Here, we report that a noted B cell antigen, the algae protein-phycoerythrin (PE) is an antigen for murine and human γδ T cells. PE also stained specific bovine γδ T cells. Employing this specificity, we demonstrated that antigen recognition, but not extensive clonal expansion, was required to activate naïve γδ T cells to make IL-17. In this activated state, γδ T cells gained the ability to respond to cytokine signals that perpetuated the IL-17 production. These results underscore the adaptability of lymphocyte antigen receptors and suggest a previously unrecognized antigen-driven rapid response in protective immunity prior to the maturation of classical adaptive immunity. PMID:22960222

  20. γδ T cells recognize a microbial encoded B cell antigen to initiate a rapid antigen-specific interleukin-17 response.

    Science.gov (United States)

    Zeng, Xun; Wei, Yu-Ling; Huang, Jun; Newell, Evan W; Yu, Hongxiang; Kidd, Brian A; Kuhns, Michael S; Waters, Ray W; Davis, Mark M; Weaver, Casey T; Chien, Yueh-hsiu

    2012-09-21

    γδ T cells contribute uniquely to immune competence. Nevertheless, how they function remains an enigma. It is unclear what most γδ T cells recognize, what is required for them to mount an immune response, and how the γδ T cell response is integrated into host immune defense. Here, we report that a noted B cell antigen, the algae protein phycoerythrin (PE), is a murine and human γδ T cell antigen. Employing this specificity, we demonstrated that antigen recognition activated naive γδ T cells to make interleukin-17 and respond to cytokine signals that perpetuate the response. High frequencies of antigen-specific γδ T cells in naive animals and their ability to mount effector response without extensive clonal expansion allow γδ T cells to initiate a swift, substantial response. These results underscore the adaptability of lymphocyte antigen receptors and suggest an antigen-driven rapid response in protective immunity prior to the maturation of classical adaptive immunity. PMID:22960222

  1. Evaluation of milk yield in tsigaiewes by somatic cell count

    Directory of Open Access Journals (Sweden)

    Martina Vršková

    2015-08-01

    Full Text Available The objective of our research was to study daily milk production which was affected by somatic cell count (SCC. The study was performed on a selected flock of purebred Tsigai ewes (326 animals. Regular milk yield recording was performed during the evening milking in around the middle of April, May and June. Milk samples were analyzed for basic milk composition (fat, protein and lactose and somatic cells count. SCC were evaluated using decadic logarithm (logSCC.According to animals, the dairy ewes were divided into the four groups on the basis of individual SCC (G1 = SCC <100 × 103 cells.mL-1, G2 = SCC between 100 – 300 × 103 cells.mL-1, G3 = SCC between 300 – 600 × 103 cells.mL-1, G4 = SCC >600 × 103 cells.mL-1 to study the frequency of distribution of animals in selected group of ewes throughout experimental period. The average daily milk production in selected flock of Tsigai was 421.02 mL. We reached the highest daily milk production in April 476.40 ml and the highest content of fat and protein in June, while milk production was the lowest. From this flock of purebred Tsigai 76% of eweswere below SCC 300 × 103 cells.mL-1. This SCC indicated a good health status of experimental ewes, at which 61% sheep were at the first lactation. We found a tendency to lower milk production by a higher SCC. With the increasing SCC decreased lactose content from 4.78% (G1 to 4.32% (G4. Reduced lactose content refers to the occurrence of mastitis and there is a need for performing bacteriological examination in milk.

  2. Helicobacter pylori Disrupts Host Cell Membranes, Initiating a Repair Response and Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Hsueh-Fen Juan

    2012-08-01

    Full Text Available Helicobacter pylori (H. pylori, the human stomach pathogen, lives on the inner surface of the stomach and causes chronic gastritis, peptic ulcer, and gastric cancer. Plasma membrane repair response is a matter of life and death for human cells against physical and biological damage. We here test the hypothesis that H. pylori also causes plasma membrane disruption injury, and that not only a membrane repair response but also a cell proliferation response are thereby activated. Vacuolating cytotoxin A (VacA and cytotoxin-associated gene A (CagA have been considered to be major H. pylori virulence factors. Gastric cancer cells were infected with H. pylori wild type (vacA+/cagA+, single mutant (ΔvacA or ΔcagA or double mutant (ΔvacA/ΔcagA strains and plasma membrane disruption events and consequent activation of membrane repair components monitored. H. pylori disrupts the host cell plasma membrane, allowing localized dye and extracellular Ca2+ influx. Ca2+-triggered members of the annexin family, A1 and A4, translocate, in response to injury, to the plasma membrane, and cell surface expression of an exocytotic maker of repair, LAMP-2, increases. Additional forms of plasma membrane disruption, unrelated to H. pylori exposure, also promote host cell proliferation. We propose that H. pylori activation of a plasma membrane repair is pro-proliferative. This study might therefore provide new insight into potential mechanisms of H. pylori-induced gastric carcinogenesis.

  3. AN EVALUATION OF THE SAFETY OF ADIPOSE-DERIVED STEM CELLS

    Directory of Open Access Journals (Sweden)

    Ngoc Bich Vu

    2015-09-01

    Full Text Available The adipose tissue contains a large numbers of stem cells; adipose-derived stem cells (ADSCs can be em- ployed in regenerative medicine. This study was aimed at isolating ADSCs and evaluating the safety of ADSCs in mouse models. Stromal vascular fraction (SVF was collected from the adipose tissue using collagenase. ADSCs were then isolated from SVFs by in vitro culture. The stemness of the ADSCs was evaluated in vitro based on their self-renewal potential, po- tential to differentiate into osteoblasts, and adipocytes, and the expression of specific markers. Finally, the tumor forma- tion ability of ADSCs was evaluated in vivo in athymic mice. Results showed that 100% of the ADSC samples developed well and maintained homogeneity up to passage 10. The ADSCs were completely sterilized and could not form tumors in athymic mice. These initial results showed that ADSCs were safe for use in stem cell therapy. [Biomed Res Ther 2015; 2(9.000: 359-365

  4. Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity

    DEFF Research Database (Denmark)

    Kim, Jiyoung; Villadsen, René; Sørlie, Therese;

    2012-01-01

    The majority of human breast cancers exhibit luminal epithelial differentiation. However, most aggressive behavior, including invasion and purported cancer stem cell activity, are considered characteristics of basal-like cells. We asked the following questions: Must luminal-like breast cancer cells...... become basal-like to initiate tumors or to invade? Could luminally differentiated cells within a basally initiated hierarchy also be tumorigenic? To answer these questions, we used rare and mutually exclusive lineage markers to isolate subsets of luminal-like and basal-like cells from human breast tumors....... We enriched for populations with or without prominent basal-like traits from individual tumors or single cell cloning from cell lines and recovered cells with a luminal-like phenotype. Tumor cells with basal-like traits mimicked phenotypic and functional behavior associated with stem cells assessed...

  5. DNA Amplification by Breakage/Fusion/Bridge Cycles Initiated by Spontaneous Telomere Loss in a Human Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Anthony W.l. Lo

    2002-01-01

    Full Text Available The development of genomic instability is an important step in generatingthe multiple genetic changes required for cancer. One consequence of genomic instability is the overexpression of oncogenes due to gene amplification. One mechanism for gene amplification is the breakagelfusionlbridge (B/F/Bcyclethatinvolvesthe repeated fusion and breakage of chromosomes following the loss of a telomere. B/F/B cycles have been associated with low-copy gene amplification in human cancer cells, and have been proposed to be an initiating event in high-copy gene amplification. We have found that spontaneous telomere loss on a marker chromosome 16 in a human tumor cell line results in sister chromatid fusion and prolonged periods of chromosome instability. The high rate of anaphase bridges involving chromosome 16 demonstrates that this instability results from B/F/B cycles. The amplification of subtelomeric DNA on the marker chromosome provides conclusive evidence that B/F/B cycles initiated by spontaneous telomere loss are a mechanism for gene amplification in human cancer cells.

  6. AHP6 inhibits cytokinin signaling to regulate the orientation of pericycle cell division during lateral root initiation.

    Directory of Open Access Journals (Sweden)

    Sofia Moreira

    Full Text Available In Arabidopsis thaliana, lateral roots (LRs initiate from anticlinal cell divisions of pericycle founder cells. The formation of LR primordia is regulated antagonistically by the phytohormones cytokinin and auxin. It has previously been shown that cytokinin has an inhibitory effect on the patterning events occurring during LR formation. However, the molecular players involved in cytokinin repression are still unknown. In a similar manner to protoxylem formation in Arabidopsis roots, in which AHP6 (ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER PROTEIN 6 acts as a cytokinin inhibitor, we reveal that AHP6 also functions as a cytokinin repressor during early stages of LR development. We show that AHP6 is expressed at different developmental stages during LR formation and is required for the correct orientation of cell divisions at the onset of LR development. Moreover, we demonstrate that AHP6 influences the localization of the auxin efflux carrier PIN1, which is necessary for patterning the LR primordia. In summary, we show that the inhibition of cytokinin signaling through AHP6 is required to establish the correct pattern during LR initiation.

  7. p38α Activates Purine Metabolism to Initiate Hematopoietic Stem/Progenitor Cell Cycling in Response to Stress.

    Science.gov (United States)

    Karigane, Daiki; Kobayashi, Hiroshi; Morikawa, Takayuki; Ootomo, Yukako; Sakai, Mashito; Nagamatsu, Go; Kubota, Yoshiaki; Goda, Nobuhito; Matsumoto, Michihiro; Nishimura, Emi K; Soga, Tomoyoshi; Otsu, Kinya; Suematsu, Makoto; Okamoto, Shinichiro; Suda, Toshio; Takubo, Keiyo

    2016-08-01

    Hematopoietic stem cells (HSCs) maintain quiescence by activating specific metabolic pathways, including glycolysis. We do not yet have a clear understanding of how this metabolic activity changes during stress hematopoiesis, such as bone marrow transplantation. Here, we report a critical role for the p38MAPK family isoform p38α in initiating hematopoietic stem and progenitor cell (HSPC) proliferation during stress hematopoiesis in mice. We found that p38MAPK is immediately phosphorylated in HSPCs after a hematological stress, preceding increased HSPC cycling. Conditional deletion of p38α led to defective recovery from hematological stress and a delay in initiation of HSPC proliferation. Mechanistically, p38α signaling increases expression of inosine-5'-monophosphate dehydrogenase 2 in HSPCs, leading to altered levels of amino acids and purine-related metabolites and changes in cell-cycle progression in vitro and in vivo. Our studies have therefore uncovered a p38α-mediated pathway that alters HSPC metabolism to respond to stress and promote recovery. PMID:27345838

  8. The Nanomaterial Data Curation Initiative: A collaborative approach to assessing, evaluating, and advancing the state of the field

    Directory of Open Access Journals (Sweden)

    Christine Ogilvie Hendren

    2015-08-01

    Full Text Available The Nanomaterial Data Curation Initiative (NDCI, a project of the National Cancer Informatics Program Nanotechnology Working Group (NCIP NanoWG, explores the critical aspect of data curation within the development of informatics approaches to understanding nanomaterial behavior. Data repositories and tools for integrating and interrogating complex nanomaterial datasets are gaining widespread interest, with multiple projects now appearing in the US and the EU. Even in these early stages of development, a single common aspect shared across all nanoinformatics resources is that data must be curated into them. Through exploration of sub-topics related to all activities necessary to enable, execute, and improve the curation process, the NDCI will provide a substantive analysis of nanomaterial data curation itself, as well as a platform for multiple other important discussions to advance the field of nanoinformatics. This article outlines the NDCI project and lays the foundation for a series of papers on nanomaterial data curation. The NDCI purpose is to: 1 present and evaluate the current state of nanomaterial data curation across the field on multiple specific data curation topics, 2 propose ways to leverage and advance progress for both individual efforts and the nanomaterial data community as a whole, and 3 provide opportunities for similar publication series on the details of the interactive needs and workflows of data customers, data creators, and data analysts. Initial responses from stakeholder liaisons throughout the nanoinformatics community reveal a shared view that it will be critical to focus on integration of datasets with specific orientation toward the purposes for which the individual resources were created, as well as the purpose for integrating multiple resources. Early acknowledgement and undertaking of complex topics such as uncertainty, reproducibility, and interoperability is proposed as an important path to addressing key

  9. Molecular Classification and Pharmacogenetics of Primary Plasma Cell Leukemia: An Initial Approach toward Precision Medicine.

    Science.gov (United States)

    Simeon, Vittorio; Todoerti, Katia; La Rocca, Francesco; Caivano, Antonella; Trino, Stefania; Lionetti, Marta; Agnelli, Luca; De Luca, Luciana; Laurenzana, Ilaria; Neri, Antonino; Musto, Pellegrino

    2015-07-30

    Primary plasma cell leukemia (pPCL) is a rare and aggressive variant of multiple myeloma (MM) which may represent a valid model for high-risk MM. This disease is associated with a very poor prognosis, and unfortunately, it has not significantly improved during the last three decades. New high-throughput technologies have allowed a better understanding of the molecular basis of this disease and moved toward risk stratification, providing insights for targeted therapy studies. This knowledge, added to the pharmacogenetic profile of new and old agents in the analysis of efficacy and safety, could contribute to help clinical decisions move toward a precision medicine and a better clinical outcome for these patients. In this review, we describe the available literature concerning the genomic characterization and pharmacogenetics of plasma cell leukemia (PCL).

  10. Molecular Classification and Pharmacogenetics of Primary Plasma Cell Leukemia: An Initial Approach toward Precision Medicine

    Directory of Open Access Journals (Sweden)

    Vittorio Simeon

    2015-07-01

    Full Text Available Primary plasma cell leukemia (pPCL is a rare and aggressive variant of multiple myeloma (MM which may represent a valid model for high-risk MM. This disease is associated with a very poor prognosis, and unfortunately, it has not significantly improved during the last three decades. New high-throughput technologies have allowed a better understanding of the molecular basis of this disease and moved toward risk stratification, providing insights for targeted therapy studies. This knowledge, added to the pharmacogenetic profile of new and old agents in the analysis of efficacy and safety, could contribute to help clinical decisions move toward a precision medicine and a better clinical outcome for these patients. In this review, we describe the available literature concerning the genomic characterization and pharmacogenetics of plasma cell leukemia (PCL.

  11. Molecular Classification and Pharmacogenetics of Primary Plasma Cell Leukemia: An Initial Approach toward Precision Medicine.

    Science.gov (United States)

    Simeon, Vittorio; Todoerti, Katia; La Rocca, Francesco; Caivano, Antonella; Trino, Stefania; Lionetti, Marta; Agnelli, Luca; De Luca, Luciana; Laurenzana, Ilaria; Neri, Antonino; Musto, Pellegrino

    2015-01-01

    Primary plasma cell leukemia (pPCL) is a rare and aggressive variant of multiple myeloma (MM) which may represent a valid model for high-risk MM. This disease is associated with a very poor prognosis, and unfortunately, it has not significantly improved during the last three decades. New high-throughput technologies have allowed a better understanding of the molecular basis of this disease and moved toward risk stratification, providing insights for targeted therapy studies. This knowledge, added to the pharmacogenetic profile of new and old agents in the analysis of efficacy and safety, could contribute to help clinical decisions move toward a precision medicine and a better clinical outcome for these patients. In this review, we describe the available literature concerning the genomic characterization and pharmacogenetics of plasma cell leukemia (PCL). PMID:26263974

  12. Molecular Classification and Pharmacogenetics of Primary Plasma Cell Leukemia: An Initial Approach toward Precision Medicine

    Science.gov (United States)

    Simeon, Vittorio; Todoerti, Katia; La Rocca, Francesco; Caivano, Antonella; Trino, Stefania; Lionetti, Marta; Agnelli, Luca; De Luca, Luciana; Laurenzana, Ilaria; Neri, Antonino; Musto, Pellegrino

    2015-01-01

    Primary plasma cell leukemia (pPCL) is a rare and aggressive variant of multiple myeloma (MM) which may represent a valid model for high-risk MM. This disease is associated with a very poor prognosis, and unfortunately, it has not significantly improved during the last three decades. New high-throughput technologies have allowed a better understanding of the molecular basis of this disease and moved toward risk stratification, providing insights for targeted therapy studies. This knowledge, added to the pharmacogenetic profile of new and old agents in the analysis of efficacy and safety, could contribute to help clinical decisions move toward a precision medicine and a better clinical outcome for these patients. In this review, we describe the available literature concerning the genomic characterization and pharmacogenetics of plasma cell leukemia (PCL). PMID:26263974

  13. Activated alveolar epithelial cells initiate fibrosis through autocrine and paracrine secretion of connective tissue growth factor

    OpenAIRE

    Yang, Jibing; Velikoff, Miranda; Canalis, Ernesto; Horowitz, Jeffrey C.; Kim, Kevin K.

    2014-01-01

    Fibrogenesis involves a pathological accumulation of activated fibroblasts and extensive matrix remodeling. Profibrotic cytokines, such as TGF-β, stimulate fibroblasts to overexpress fibrotic matrix proteins and induce further expression of profibrotic cytokines, resulting in progressive fibrosis. Connective tissue growth factor (CTGF) is a profibrotic cytokine that is indicative of fibroblast activation. Epithelial cells are abundant in the normal lung, but their contribution to fibrogenesis...

  14. Melittin initiates dopamine transporter internalization and recycling in transfected HEK-293 cells

    OpenAIRE

    Keith, Dove J; Wolfrum, Katherine; Eshleman, Amy J; Janowsky, Aaron

    2012-01-01

    The dopamine transporter removes the neurotransmitter from the synapse, regulating dopamine availability. The transporter can be internalized and its function is blocked by cocaine and other ligands. Melittin inhibits dopamine transporter function and causes internalization of the recombinant transporter in stably transfected HEK-293 cells, but the specific pathways for internalization and disposition of the transporter are unknown. Here we report that melittin treatment increased both transp...

  15. N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells

    OpenAIRE

    Lee, JK; Phillips, JW; Smith, BA; Park, JW; Stoyanova, T; McCaffrey, EF; Baertsch, R.; Sokolov, A.; Meyerowitz, JG; Mathis, C.; Cheng, D; Stuart, JM; Shokat, KM; Gustafson, WC; Huang, J.

    2016-01-01

    MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarci...

  16. Molecular classification and pharmacogenetics of primary plasma cell leukemia: an initial approach toward precision medicine

    OpenAIRE

    Vittorio Simeon; Katia Todoerti; Francesco La Rocca; Antonella Caivano; Stefania Trino; Marta Lionetti; Luca Agnelli; Luciana De Luca; Ilaria Laurenzana; Antonino Neri; Pellegrino Musto

    2015-01-01

    Primary plasma cell leukemia (pPCL) is a rare and aggressive variant of multiple myeloma (MM) which may represent a valid model for high-risk MM. This disease is associated with a very poor prognosis, and unfortunately, it has not significantly improved during the last three decades. New high-throughput technologies have allowed a better understanding of the molecular basis of this disease and moved toward risk stratification, providing insights for targeted therapy studies. This knowledge, ...

  17. Brief dendritic calcium signals initiate long-lasting synaptic depression in cerebellar Purkinje cells.

    OpenAIRE

    Konnerth, A.; Dreessen, J; Augustine, G J

    1992-01-01

    We have performed experiments designed to test the hypothesis that long-term depression (LTD) of excitatory synaptic transmission in the cerebellar cortex is caused by a rise in postsynaptic Ca concentration. These experiments combined measurements of synaptic efficacy, performed with the thin slice patch clamp technique, with fura-2 measurements of intracellular Ca concentration ([Ca]i) in single cerebellar Purkinje cells. Simultaneous activation of the climbing fiber and parallel fibers inn...

  18. Potential effect of matrix stiffness on the enrichment of tumor initiating cells under three-dimensional culture conditions.

    Science.gov (United States)

    Liu, Chang; Liu, Yang; Xu, Xiao-xi; Wu, Hao; Xie, Hong-guo; Chen, Li; Lu, Ting; Yang, Li; Guo, Xin; Sun, Guang-wei; Wang, Wei; Ma, Xiao-jun; He, Xin

    2015-01-01

    Cancer stem cell (CSC) or tumor initiating cell (TIC) plays an important role in tumor progression and metastasis. Biophysical forces in tumor microenvironment have an important effect on tumor formation and development. In this study, the potential effect of matrix stiffness on the biological characteristics of human head and neck squamous cell carcinoma (HNSCC) TICs, especially the enrichment of HNSCC TICs, was investigated under three-dimensional (3D) culture conditions by means of alginate gel (ALG) beads with different matrix stiffnesses. ALG beads with soft (21 kPa), moderate (70 kPa) and hard (105 kPa) stiffness were generated by changing alginate concentration. It was found that significant HNSCC TIC enrichment was achieved in the ALG beads with moderate matrix stiffness (70 kPa). The gene expression of stemness markers Oct3/4 and Nanog, TIC markers CD44 and ABCG2 was enhanced in cells under this moderate (70 kPa) stiffness. HNSCC TIC proportion was also highly enriched under moderate matrix stiffness, accompanying with higher tumorigenicity, metastatic ability and drug resistance. And it was also found that the possible molecular mechanism underlying the regulated TIC properties by matrix stiffness under 3D culture conditions was significantly different from 2D culture condition. Therefore, the results achieved in this study indicated that 3D biophysical microenvironment had an important effect on TIC characteristics and alginate-based biomimetic scaffolds could be utilized as a proper platform to investigate the interaction between tumor cells and 3D microenvironment.

  19. Tumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression

    Science.gov (United States)

    Zhang, Wen Cai; Chin, Tan Min; Yang, Henry; Nga, Min En; Lunny, Declan Patrick; Lim, Edwin Kok Hao; Sun, Li Li; Pang, Yin Huei; Leow, Yi Ning; Malusay, Shanneen Rossellini Y; Lim, Priscilla Xin Hui; Lee, Jeravan Zili; Tan, Benedict Jian Wei; Shyh-Chang, Ng; Lim, Elaine Hsuen; Lim, Wan Teck; Tan, Daniel Shao Weng; Tan, Eng Huat; Tai, Bee Choo; Soo, Ross Andrew; Tam, Wai Leong; Lim, Bing

    2016-01-01

    The tumour-initiating cell (TIC) model accounts for phenotypic and functional heterogeneity among tumour cells. MicroRNAs (miRNAs) are regulatory molecules frequently aberrantly expressed in cancers, and may contribute towards tumour heterogeneity and TIC behaviour. More recent efforts have focused on miRNAs as diagnostic or therapeutic targets. Here, we identified the TIC-specific miRNAs, miR-1246 and miR-1290, as crucial drivers for tumour initiation and cancer progression in human non-small cell lung cancer. The loss of either miRNA impacted the tumour-initiating potential of TICs and their ability to metastasize. Longitudinal analyses of serum miR-1246 and miR-1290 levels across time correlate their circulating levels to the clinical response of lung cancer patients who were receiving ongoing anti-neoplastic therapies. Functionally, direct inhibition of either miRNA with locked nucleic acid administered systemically, can arrest the growth of established patient-derived xenograft tumours, thus indicating that these miRNAs are clinically useful as biomarkers for tracking disease progression and as therapeutic targets. PMID:27325363

  20. Endogenous synchronous fluorescence spectroscopy (SFS) of basal cell carcinoma-initial study

    Science.gov (United States)

    Borisova, E.; Zhelyazkova, Al.; Keremedchiev, M.; Penkov, N.; Semyachkina-Glushkovskaya, O.; Avramov, L.

    2016-01-01

    The human skin is a complex, multilayered and inhomogeneous organ with spatially varying optical properties. Analysis of cutaneous fluorescence spectra could be a very complicated task; therefore researchers apply complex mathematical tools for data evaluation, or try to find some specific approaches, that would simplify the spectral analysis. Synchronous fluorescence spectroscopy (SFS) allows improving the spectral resolution, which could be useful for the biological tissue fluorescence characterization and could increase the tumour detection diagnostic accuracy.

  1. Initial Presentation of Renal Cell Carcinoma as a Metastatic Mass within the Masseter Muscle: A Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Kyung Eun; Lee, Han Bee; Cho, Woo Ho; Kim, Jae Hyung; Lee, Ji Hae; Kang, Min Jin [Dept. of Radiology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of); Kim, Hyun Jung [Dept. of Pathology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of)

    2012-02-15

    Renal cell carcinoma (RCC) is often concomitant with distant metastasis, and these metastases are the first sign of an otherwise occult primary. Whereas metastasis of RCC to the head and neck has been reported, metastasis to the masseter muscle, which is composed of skeletal muscle, is quite rare. We now report the case of a 66-year-old man who had a past history of pulmonary tuberculosis, with RCC metastasis of a well-defined intensely enhancing hypervascular mass in the masseter muscle as the initial presentation. We present the imaging findings of this case and a literature review about radiologic differential diagnosis of intramasseteric masses.

  2. Lung cancer tumorigenicity and drug resistance are maintained through ALDH(hi)CD44(hi) tumor initiating cells.

    Science.gov (United States)

    Liu, Jing; Xiao, Zhijie; Wong, Sunny Kit-Man; Tin, Vicky Pui-Chi; Ho, Ka-Yan; Wang, Junwen; Sham, Mai-Har; Wong, Maria Pik

    2013-10-01

    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 patient-derived lung cancer cells. The ALDH(hi)CD44(hi) subset showed the highest enhancement of stem cell phenotypic properties compared to ALDH(hi)CD44(lo), ALDH(lo)CD44(hi), ALDH(lo)CD44(lo) cells and unsorted controls. They showed higher invasion capacities, pluripotency genes and epithelial-mesenchymal transition transcription factors expression, lower intercellular adhesion protein expression and higher G2/M phase cell cycle fraction. In immunosuppressed mice, the ALDH(hi)CD44(hi)xenografts showed the highest tumor induction frequency, serial transplantability, shortest latency, largest volume and highest growth rates. Inhibition of sonic Hedgehog and Notch developmental pathways reduced ALDH+CD44+ compartment. Chemotherapy and targeted therapy resulted in higher AALDH(hi)CD44(hi) subset viability and ALDH(lo)CD44(lo) subset apoptosis fraction. ALDH inhibition and CD44 knockdown led to reduced stemness gene expression and sensitization to drug treatment. In accordance, clinical lung cancers containing a higher abundance of ALDH and CD44-coexpressing cells was associated with lower recurrence-free survival. Together, results suggested theALDH(hi)CD44(hi)compartment was the cellular mediator of tumorigenicity and drug resistance. Further investigation of the regulatory mechanisms underlying ALDH(hi)CD44(hi)TIC maintenance would be beneficial for the development of long term lung cancer control.

  3. Retreatment with Epidermal Growth Factor Receptor Inhibitor After Initial Failure in Advanced Non-small Cell Lung Cancer

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    Tongtong AN

    2011-03-01

    Full Text Available Background and objective The epidermal growth factor receptor tyrosine kinase inhibitor (EGFRTKI shows favorable antitumor activity against chemorefractory non-small cell lung cancer (NSCLC. However, patients with advanced NSCLC have limited treatment options available if they are refractory to EGFR-TKI. To study the influence of the retreatment EGFR-TKI after failure of first-line TKI, we carried out this retrospective study. Methods Total 71 patients were analyzed who experienced treatment failure from their initial use of EGFR-TKI. After a period of time, they were retreated with TKI as tumor progression was observed. Results Of the 71 patients who received retreatment TKI, it was observed in 7% in partial response (PR, 36.6% in stable disease (SD, 56.3% in progressive disease (PD. Disease control rate (DCR was 43.7%. Twenty-six (36.6% patients were well controlled by retreatment with TKI monotherapy for not less than 3 months. Five (7.0% patients had partial response. Exon 21 mutation, PFS not less than 6 months during initial treatment TKI, and the interval not less than 3 months between initial treatment, and retreatment with TKI was associated with a good progression free survival based on univariate COX analysis (P=0.034; P=0.013; P=0.046. Conclusion It has been shown the possibility that retreatment with TKI might be useful when (1 Exon 21 has active mutation, (2 initial treatment shows a favorable PFS (≥ 6 months, and (3 there has been a period of time (≥3 months following the termination of the initial TKI treatment.

  4. MSH3-deficiency initiates EMAST without oncogenic transformation of human colon epithelial cells.

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    Christoph Campregher

    Full Text Available BACKGROUND/AIM: Elevated microsatellite instability at selected tetranucleotide repeats (EMAST is a genetic signature in certain cases of sporadic colorectal cancer and has been linked to MSH3-deficiency. It is currently controversial whether EMAST is associated with oncogenic properties in humans, specifically as cancer development in Msh3-deficient mice is not enhanced. However, a mutator phenotype is different between species as the genetic positions of repetitive sequences are not conserved. Here we studied the molecular effects of human MSH3-deficiency. METHODS: HCT116 and HCT116+chr3 (both MSH3-deficient and primary human colon epithelial cells (HCEC, MSH3-wildtype were stably transfected with an EGFP-based reporter plasmid for the detection of frameshift mutations within an [AAAG]17 repeat. MSH3 was silenced by shRNA and changes in protein expression were analyzed by shotgun proteomics. Colony forming assay was used to determine oncogenic transformation and double strand breaks (DSBs were assessed by Comet assay. RESULTS: Despite differential MLH1 expression, both HCT116 and HCT116+chr3 cells displayed comparable high mutation rates (about 4×10(-4 at [AAAG]17 repeats. Silencing of MSH3 in HCECs leads to a remarkable increased frameshift mutations in [AAAG]17 repeats whereas [CA]13 repeats were less affected. Upon MSH3-silencing, significant changes in the expression of 202 proteins were detected. Pathway analysis revealed overexpression of proteins involved in double strand break repair (MRE11 and RAD50, apoptosis, L1 recycling, and repression of proteins involved in metabolism, tRNA aminoacylation, and gene expression. MSH3-silencing did not induce oncogenic transformation and DSBs increased 2-fold. CONCLUSIONS: MSH3-deficiency in human colon epithelial cells results in EMAST, formation of DSBs and significant changes of the proteome but lacks oncogenic transformation. Thus, MSH3-deficiency alone is unlikely to drive human colon

  5. Initial evaluation in healthy humans of [18F]DPA-714, a potential PET biomarker for neuroinflammation

    International Nuclear Information System (INIS)

    Introduction: The translocator protein 18 kDa (TSPO), although minimally expressed in healthy brain, is up-regulated in pathological conditions, coinciding with microglial activation. It is thereby a suitable in vivo biomarker of neuroinflammation for detection, evaluation and therapeutic monitoring of brain diseases. We aimed to estimate the radiation dosimetry of the positron emission tomography (PET) TSPO radioligand [18F]DPA-714, and we evaluated in healthy volunteers its whole-body uptake and cerebral kinetics. Methods: Biodistribution data from mice were used for the prediction of radiation dosimetry. In human studies, a 90-min dynamic PET scan was performed in seven healthy volunteers after injection of [18F]DPA-714 (245±45 MBq). Arterial and venous samples were collected from two subjects, and two additional subjects were submitted to whole-body acquisition. Regions of interest were defined over cerebral structures to obtain mean time–activity curves and to estimate the distribution volume ratios by Logan graphical analysis, and over peripheral organs to obtain standard uptake values. Results: The effective dose estimated from biodistribution in mice was 17.2 μSv/MBq. Modeling of regional brain and plasma data showed good in vivo stability of [18F]DPA-714 in humans, with only 20% of blood metabolites 20 min postinjection (p.i.). Maximum cerebral uptake was observed 5 min p.i., followed by two decreasing phases: a rapid washout (5–30 min) followed by a slower phase for the remainder of PET acquisition. Whole-body images demonstrate high activity in the gallbladder, heart, spleen and kidneys. Conclusions: This initial study in humans shows that [18F]DPA-714 is a promising PET radioligand with excellent in vivo stability and biodistribution, and acceptable effective dose estimation. Therefore, [18F]DPA-714 could provide a sensitive measure of neuroinflammatory changes in subsequent clinical investigations.

  6. Trends of CD4 cell count levels at the initiation of antiretroviral therapy over time and factors associated with late initiation of antiretroviral therapy among Asian HIV-positive patients

    Directory of Open Access Journals (Sweden)

    Sasisopin Kiertiburanakul

    2014-03-01

    Full Text Available Introduction: Although antiretroviral therapy (ART has been rapidly scaled up in Asia, most HIV-positive patients in the region still present with late-stage HIV disease. We aimed to determine trends of pre-ART CD4 levels over time in Asian HIV-positive patients and to determine factors associated with late ART initiation. Methods: Data from two regional cohort observational databases were analyzed for trends in median CD4 cell counts at ART initiation and the proportion of late ART initiation (CD4 cell counts <200 cells/mm3 or prior AIDS diagnosis. Predictors for late ART initiation and mortality were determined. Results: A total of 2737 HIV-positive ART-naïve patients from 22 sites in 13 Asian countries and territories were eligible. The overall median (IQR CD4 cell count at ART initiation was 150 (46–241 cells/mm3. Median CD4 cell counts at ART initiation increased over time, from a low point of 115 cells/mm3 in 2008 to a peak of 302 cells/mm3 after 2011 (p for trend 0.002. The proportion of patients with late ART initiation significantly decreased over time from 79.1% before 2007 to 36.3% after 2011 (p for trend <0.001. Factors associated with late ART initiation were year of ART initiation (e.g. 2010 vs. before 2007; OR 0.40, 95% CI 0.27–0.59; p<0.001, sex (male vs. female; OR 1.51, 95% CI 1.18–1.93; p=0.001 and HIV exposure risk (heterosexual vs. homosexual; OR 1.66, 95% CI 1.24–2.23; p=0.001 and intravenous drug use vs. homosexual; OR 3.03, 95% CI 1.77–5.21; p<0.001. Factors associated with mortality after ART initiation were late ART initiation (HR 2.13, 95% CI 1.19–3.79; p=0.010, sex (male vs. female; HR 2.12, 95% CI 1.31–3.43; p=0.002, age (≥51 vs. ≤30 years; HR 3.91, 95% CI 2.18–7.04; p<0.001 and hepatitis C serostatus (positive vs. negative; HR 2.48, 95% CI 1.−4.36; p=0.035. Conclusions: Median CD4 cell count at ART initiation among Asian patients significantly increases over time but the proportion of patients

  7. A Systematic Evaluation Model for Solar Cell Technologies

    Directory of Open Access Journals (Sweden)

    Chang-Fu Hsu

    2014-01-01

    Full Text Available Fossil fuels, including coal, petroleum, natural gas, and nuclear energy, are the primary electricity sources currently. However, with depletion of fossil fuels, global warming, nuclear crisis, and increasing environmental consciousness, the demand for renewable energy resources has skyrocketed. Solar energy is one of the most popular renewable energy resources for meeting global energy demands. Even though there are abundant studies on various solar technology developments, there is a lack of studies on solar technology evaluation and selection. Therefore, this research develops a model using interpretive structural modeling (ISM, benefits, opportunities, costs, and risks concept (BOCR, and fuzzy analytic network process (FANP to aggregate experts' opinions in evaluating current available solar cell technology. A case study in a photovoltaics (PV firm is used to examine the practicality of the proposed model in selecting the most suitable technology for the firm in manufacturing new products.

  8. Role of multidisciplinary approach in a case of Langerhans cell histiocytosis with initial periodontal manifestations

    Science.gov (United States)

    Cisternino, Angelo; Asa’ad, Farah; Fusco, Nicola; Ferrero, Stefano; Rasperini, Giulio

    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 periodontitis, and necrotizing ulcerative periodontitis. Case presentation: A 32-years old female visited a private dental practice with a chief complaint of sensitivity in the mandibular left first molar. Clinical and radiographic examination revealed deep periodontal pocket, recession, furcation involvement, mobility, severe alveolar bone destruction and a diagnosis of aggressive periodontitis was rendered. Multiple tooth extractions were carried out due to progressive periodontal destruction with impaired healing and development of ulcerative lesions. Multidisciplinary investigation demonstrated that the periodontal involvement was a manifestation of an underlying systemic disease. A biopsy of a bone lesion was therefore performed, revealing the presence of multifocal single system LCH. Conclusion: The identification of periodontal LCH is not trivial given that it may clinically resemble other periodontal disease entities. The dentist can be the first health care personnel to unravel the presence of an underlying systemic LCH. PMID:26722570

  9. Cathepsin B Activity Initiates Apoptosis via Digestive Protease Activation in Pancreatic Acinar Cells and Experimental Pancreatitis.

    Science.gov (United States)

    Sendler, Matthias; Maertin, Sandrina; John, Daniel; Persike, Maria; Weiss, F Ulrich; Krüger, Burkhard; Wartmann, Thomas; Wagh, Preshit; Halangk, Walter; Schaschke, Norbert; Mayerle, Julia; Lerch, Markus M

    2016-07-01

    Pancreatitis is associated with premature activation of digestive proteases in the pancreas. The lysosomal hydrolase cathepsin B (CTSB) is a known activator of trypsinogen, and its deletion reduces disease severity in experimental pancreatitis. Here we studied the activation mechanism and subcellular compartment in which CTSB regulates protease activation and cellular injury. Cholecystokinin (CCK) increased the activity of CTSB, cathepsin L, trypsin, chymotrypsin, and caspase 3 in vivo and in vitro and induced redistribution of CTSB to a secretory vesicle-enriched fraction. Neither CTSB protein nor activity redistributed to the cytosol, where the CTSB inhibitors cystatin-B/C were abundantly present. Deletion of CTSB reduced and deletion of cathepsin L increased intracellular trypsin activation. CTSB deletion also abolished CCK-induced caspase 3 activation, apoptosis-inducing factor, as well as X-linked inhibitor of apoptosis protein degradation, but these depended on trypsinogen activation via CTSB. Raising the vesicular pH, but not trypsin inhibition, reduced CTSB activity. Trypsin inhibition did not affect apoptosis in hepatocytes. Deletion of CTSB affected apoptotic but not necrotic acinar cell death. In summary, CTSB in pancreatitis undergoes activation in a secretory, vesicular, and acidic compartment where it activates trypsinogen. Its deletion or inhibition regulates acinar cell apoptosis but not necrosis in two models of pancreatitis. Caspase 3-mediated apoptosis depends on intravesicular trypsinogen activation induced by CTSB, not CTSB activity directly, and this mechanism is pancreas-specific. PMID:27226576

  10. Similar GABAA receptor subunit composition in somatic and axon initial segment synapses of hippocampal pyramidal cells.

    Science.gov (United States)

    Kerti-Szigeti, Katalin; Nusser, Zoltan

    2016-01-01

    Hippocampal pyramidal cells (PCs) express many GABAAR subunit types and receive GABAergic inputs from distinct interneurons. Previous experiments revealed input-specific differences in α1 and α2 subunit densities in perisomatic synapses, suggesting distinct IPSC decay kinetics. However, IPSC decays evoked by axo-axonic, parvalbumin- or cholecystokinin-expressing basket cells were found to be similar. Using replica immunogold labeling, here we show that all CA1 PC somatic and AIS synapses contain the α1, α2, β1, β2, β3 and γ2 subunits. In CA3 PCs, 90% of the perisomatic synapses are immunopositive for the α1 subunit and all synapses are positive for the remaining five subunits. Somatic synapses form unimodal distributions based on their immunoreactivity for these subunits. The α2 subunit densities in somatic synapses facing Cav2.1 (i.e. parvalbumin) or Cav2.2 (cholecystokinin) positive presynaptic active zones are comparable. We conclude that perisomatic synapses made by three distinct interneuron types have similar GABAA receptor subunit content. PMID:27537197

  11. Initiation of immune tolerance–controlled HIV gp41 neutralizing B cell lineages

    Science.gov (United States)

    Zhang, Ruijun; Verkoczy, Laurent; Wiehe, Kevin; Alam, S. Munir; Nicely, Nathan I.; Santra, Sampa; Bradley, Todd; Pemble, Charles W.; Zhang, Jinsong; Gao, Feng; Montefiori, David C.; Bouton-Verville, Hilary; Kelsoe, Garnett; Larimore, Kevin; Greenberg, Phillip D.; Parks, Robert; Foulger, Andrew; Peel, Jessica N.; Luo, Kan; Lu, Xiaozhi; Trama, Ashley M.; Vandergrift, Nathan; Tomaras, Georgia D.; Kepler, Thomas B.; Moody, M. Anthony; Liao, Hua-Xin; Haynes, Barton F.

    2016-01-01

    Development of an HIV vaccine is a global priority. A major roadblock to a vaccine is an inability to induce protective broadly neutralizing antibodies (bnAbs). HIV gp41 bnAbs have characteristics that predispose them to be controlled by tolerance. We used gp41 2F5 bnAb germline knock-in mice and macaques vaccinated with immunogens reactive with germline precursors to activate neutralizing antibodies. In germline knock-in mice, bnAb precursors were deleted, with remaining anergic B cells capable of being activated by germline-binding immunogens to make gp41-reactive immunoglobulin M (IgM). Immunized macaques made B cell clonal lineages targeted to the 2F5 bnAb epitope, but 2F5-like antibodies were either deleted or did not attain sufficient affinity for gp41-lipid complexes to achieve the neutralization potency of 2F5. Structural analysis of members of a vaccine-induced antibody lineage revealed that heavy chain complementarity-determining region 3 (HCDR3) hydrophobicity was important for neutralization. Thus, gp41 bnAbs are controlled by immune tolerance, requiring vaccination strategies to transiently circumvent tolerance controls. PMID:27122615

  12. A new solution for camera calibration and real-time image distortion correction in medical endoscopy-initial technical evaluation.

    Science.gov (United States)

    Melo, Rui; Barreto, João P; Falcão, Gabriel

    2012-03-01

    Medical endoscopy is used in a wide variety of diagnostic and surgical procedures. These procedures are renowned for the difficulty of orienting the camera and instruments inside the human body cavities. The small size of the lens causes radial distortion of the image, which hinders the navigation process and leads to errors in depth perception and object morphology. This article presents a complete software-based system to calibrate and correct the radial distortion in clinical endoscopy in real time. Our system can be used with any type of medical endoscopic technology, including oblique-viewing endoscopes and HD image acquisition. The initial camera calibration is performed in an unsupervised manner from a single checkerboard pattern image. For oblique-viewing endoscopes the changes in calibration during operation are handled by a new adaptive camera projection model and an algorithm that infer the rotation of the probe lens using only image information. The workload is distributed across the CPU and GPU through an optimized CPU+GPU hybrid solution. This enables real-time performance, even for HD video inputs. The system is evaluated for different technical aspects, including accuracy of modeling and calibration, overall robustness, and runtime profile. The contributions are highly relevant for applications in computer-aided surgery and image-guided intervention such as improved visualization by image warping, 3-D modeling, and visual SLAM. PMID:22127990

  13. Technical Report Series on Global Modeling and Data Assimilation, Volume 43. MERRA-2; Initial Evaluation of the Climate

    Science.gov (United States)

    Koster, Randal D. (Editor); Bosilovich, Michael G.; Akella, Santha; Lawrence, Coy; Cullather, Richard; Draper, Clara; Gelaro, Ronald; Kovach, Robin; Liu, Qing; Molod, Andrea; Norris, Peter; Wargan, Krzysztof; Chao, Winston; Reichle, Rolf; Takacs, Lawrence; Todling, Ricardo; Vikhliaev, Yury; Bloom, Steve; Collow, Allison; Partyka, Gary; Labow, Gordon; Pawson, Steven; Reale, Oreste; Schubert, Siegfried; Suarez, Max

    2015-01-01

    The years since the introduction of MERRA have seen numerous advances in the GEOS-5 Data Assimilation System as well as a substantial decrease in the number of observations that can be assimilated into the MERRA system. To allow continued data processing into the future, and to take advantage of several important innovations that could improve system performance, a decision was made to produce MERRA-2, an updated retrospective analysis of the full modern satellite era. One of the many advances in MERRA-2 is a constraint on the global dry mass balance; this allows the global changes in water by the analysis increment to be near zero, thereby minimizing abrupt global interannual variations due to changes in the observing system. In addition, MERRA-2 includes the assimilation of interactive aerosols into the system, a feature of the Earth system absent from previous reanalyses. Also, in an effort to improve land surface hydrology, observations-corrected precipitation forcing is used instead of model-generated precipitation. Overall, MERRA-2 takes advantage of numerous updates to the global modeling and data assimilation system. In this document, we summarize an initial evaluation of the climate in MERRA-2, from the surface to the stratosphere and from the tropics to the poles. Strengths and weaknesses of the MERRA-2 climate are accordingly emphasized.

  14. Reorganization of Practicum in Initial Teacher Education: A Search for Challenges in Implementation by Ex-Ante Evaluation

    Directory of Open Access Journals (Sweden)

    Laila Niklasson

    2015-10-01

    Full Text Available The background of the study is a perceived need of increasing quality in practice during Initial Teacher Education (ITE in Sweden. In order to achieve higher quality, the government encourages reorganization towards a limited number of practice schools, competence development for supervisors and research focusing on the selected practice schools.  The aim of this study is to present and critically discuss prerequisites for implementation of the reform. The paper focuses on how a preliminary logic model and a SWOT analysis can show challenges encountered during the implementation of the reorganization. By using the logic model and the SWOT analysis an ex-ante evaluation was carried out in two steps. The results disclosed that the motivation behind reorganization, improving the quality of practicum, might meet some challenges. Indicators of higher quality being attained are not provided; the local organization is expected to construct such indicators during the process. In contrast to the challenges the results showed that the implementation was supported by earlier good relations and a common idea of developing practicum in ITE. The implication for implementation is a need to have a dialogue about indicators for quality among different stakeholders in ITE. Without such a dialogue it can be disputed whether the change in practicum was successful.

  15. Development and initial evaluation of an enhanced measure of boundary flexibility for the work and family domains.

    Science.gov (United States)

    Matthews, Russell A; Barnes-Farrell, Janet L

    2010-07-01

    This manuscript reports the development of a measure of work and family domain boundary flexibility. Building on previous research, we propose an expanded definition of boundary flexibility that includes two components-flexibility-ability and flexibility-willingness-and we develop a measure designed to capture this more comprehensive definition of boundary flexibility. Flexibility-ability is conceptualized as an individual's perception of personal and situational constraints that affect boundary management, and flexibility-willingness is conceptualized as an individual difference variable that captures the motivation to engage in boundary flexing. An additional feature of domain boundaries, permeability, is also examined. Data are presented from two studies. Study 1 (N = 244) describes the development of a multiscale measure that extends current conceptual definitions of boundary flexibility. Study 2 (N = 225) describes the refinement and evaluation of this measure. Confirmatory factor analysis, reliability evidence, interscale correlations, and correlations with important work-family constructs (e.g., domain centrality, work-family conflict) provide initial construct validity evidence for the measure. PMID:20604638

  16. Evaluation of the impact of initial red wine composition on changes in color and anthocyanin content during bottle storage.

    Science.gov (United States)

    Avizcuri, José-Miguel; Sáenz-Navajas, María-Pilar; Echávarri, José-Federico; Ferreira, Vicente; Fernández-Zurbano, Purificación

    2016-12-15

    Sixteen commercial red wines, selected to cover a different range of color and total polyphenols index (TPI), were stored at 25°C during 6months under controlled and different oxygen additions (0, 1.1, 3.1, 10.6 and 30.4mgL(-1)) during the bottling process. Changes in color and the anthocyanic composition were evaluated using transmittance spectra and UPLC-MS-UV/Vis respectively. Results reveal a general pattern in the evolution of wines. However, different patterns of evolution related to initial wine composition, especially to TPI, were observed. Wines with higher TPI had a lower evolution, whereas wines with lower TPI showed a higher evolution and greater variability in behavior. In general, oxygen seemed to accelerate all changes observed during aging although the oxygen effect was more limited than the effect of the storage time. These results are relevant for wine experts and help explain the evolution of wine at the bottling stage. PMID:27451163

  17. Nonclinical evaluation of the potential for mast cell activation by an erythropoietin analog.

    Science.gov (United States)

    Weaver, James L; Boyne, Michael; Pang, Eric; Chimalakonda, Krishna; Howard, Kristina E

    2015-09-15

    The erythropoietin analog peginesatide was withdrawn from marketing due to unexpected severe anaphylactic reactions associated with administration of the multi-use formulation. The adverse events occurred rapidly following the first ever administration of the drug with most affected patients becoming symptomatic in less than 30min. This is most consistent with an anaphylactoid reaction due to direct activation of mast cells. Laboratory evaluation was undertaken using rat peritoneal mast cells as the model system. Initial studies showed that high concentrations of the formulated drug as well as formulated vehicle alone could cause mast cell degranulation as measured by histamine release. The purified active drug was not able to cause histamine release whereas the vehicle filtrate and lab created drug vehicle were equally potent at causing histamine release. Individual formulations of vehicle leaving one component out showed that histamine release was due to phenol. Dose response studies with phenol showed a very sharp dose response curve that was similar in three buffer systems. Cellular analysis by flow cytometry showed that the histamine release was not due to cell death, and that changes in light scatter parameters consistent with degranulation were rapidly observed. Limited testing with primary human mast cells showed a similar dose response of histamine release with exposure to phenol. To provide in vivo confirmation, rats were injected with vehicle formulated with various concentrations of phenol via a jugular vein cannula. Significant release of histamine was detected in blood samples taken 2min after dosing at the highest concentrations tested. PMID:26079829

  18. Enhanced Performance of Phase Change Memory Cell Element by Initial Operation and Non-Cumulative Programming

    Science.gov (United States)

    Chen, Yi-Feng; Song, Zhi-Tang; Chen, Xiao-Gang; Liu, Bo; Xu, Cheng; Feng, Gao-Ming; Wang, Liang-Yong; Zhong, Min; Feng, Song-Lin

    2010-10-01

    A phase change memory (PCM) device, based on the Ge2Sb2Te5 (GST) material, is fabricated using the standard 0.18-μm CMOS technology. After serials of detailed experiments on the phase transition behaviors, we find that the RESET process is strongly dependent on the state of the inactive area and the active area affects the SET process dramatically. By applying a 5-mA current-voltage (I — V) sweep as initial operation, we can reduce the voltage drop beyond the active area during the RESET process and the overall RESET voltage decreases from 3 V plus to 2.5 V. For the SET operation, a non-cumulative programming method is introduced to eliminate the impact of randomly formed amorphous active area, which is strongly related to the threshold switching process and SET voltage. Combining the two methods, the endurance performance of the PCM device has been remarkably improved beyond 1 × 106 cycles.

  19. A process evaluation of the scale up of a youth-friendly health services initiative in northern Tanzania

    Directory of Open Access Journals (Sweden)

    Renju Jenny

    2010-08-01

    Full Text Available Abstract Background While there are a number of examples of successful small-scale, youth-friendly services interventions aimed at improving reproductive health service provision for young people, these projects are often short term and have low coverage. In order to have a significant, long-term impact, these initiatives must be implemented over a sustained period and on a large scale. We conducted a process evaluation of the 10-fold scale up of an evaluated youth-friendly services intervention in Mwanza Region, Tanzania, in order to identify key facilitating and inhibitory factors from both user and provider perspectives. Methods The intervention was scaled up in two training rounds lasting six and 10 months. This process was evaluated through the triangulation of multiple methods: (i a simulated patient study; (ii focus group discussions and semi-structured interviews with health workers and trainers; (iii training observations; and (iv pre- and post-training questionnaires. These methods were used to compare pre- and post-intervention groups and assess differences between the two training rounds. Results Between 2004 and 2007, local government officials trained 429 health workers. The training was well implemented and over time, trainers' confidence and ability to lead sessions improved. The district-led training significantly improved knowledge relating to HIV/AIDS and puberty (RR ranged from 1.06 to 2.0, attitudes towards condoms, confidentiality and young people's right to treatment (RR range: 1.23-1.36. Intervention health units scored higher in the family planning and condom request simulated patient scenarios, but lower in the sexually transmitted infection scenario than the control health units. The scale up faced challenges in the selection and retention of trained health workers and was limited by various contextual factors and structural constraints. Conclusions Youth-friendly services interventions can remain well delivered, even

  20. Plasma-initiated rehydrogenation of amorphous silicon to increase the temperature processing window of silicon heterojunction solar cells

    Science.gov (United States)

    Shi, Jianwei; Boccard, Mathieu; Holman, Zachary

    2016-07-01

    The dehydrogenation of intrinsic hydrogenated amorphous silicon (a-Si:H) at temperatures above approximately 300 °C degrades its ability to passivate silicon wafer surfaces. This limits the temperature of post-passivation processing steps during the fabrication of advanced silicon heterojunction or silicon-based tandem solar cells. We demonstrate that a hydrogen plasma can rehydrogenate intrinsic a-Si:H passivation layers that have been dehydrogenated by annealing. The hydrogen plasma treatment fully restores the effective carrier lifetime to several milliseconds in textured crystalline silicon wafers coated with 8-nm-thick intrinsic a-Si:H layers after annealing at temperatures of up to 450 °C. Plasma-initiated rehydrogenation also translates to complete solar cells: A silicon heterojunction solar cell subjected to annealing at 450 °C (following intrinsic a-Si:H deposition) had an open-circuit voltage of less than 600 mV, but an identical cell that received hydrogen plasma treatment reached a voltage of over 710 mV and an efficiency of over 19%.