WorldWideScience

Sample records for cells escalates aggregation

  1. Biomimetic Dye Aggregate Solar Cells

    OpenAIRE

    Marek, Peter L.

    2012-01-01

    A biomimetic self-assembling dye, which forms aggregates that mimic the natural light-harvesting system of special photosynthetic active bacteria, has been investigated towards its applicability to solar cells. This fully synthetic dye, self-assembles to orderly structured nano- to micrometer sized rod-shaped aggregates, which might improve solar cells based on conventional organic dyes. In order to use the full potential of the dye aggregates, the self-assembly needed to be controlled and a ...

  2. Strategy Escalation: An emerging paradigm for safe clinical development of T cell gene therapies

    Directory of Open Access Journals (Sweden)

    Junghans Richard

    2010-06-01

    Full Text Available Abstract Gene therapy techniques are being applied to modify T cells with chimeric antigen receptors (CARs for therapeutic ends. The versatility of this platform has spawned multiple options for their application with new permutations in strategies continually being invented, a testimony to the creative energies of many investigators. The field is rapidly expanding with immense potential for impact against diverse cancers. But this rapid expansion, like the Big Bang, comes with a somewhat chaotic evolution of its therapeutic universe that can also be dangerous, as seen by recently publicized deaths. Time-honored methods for new drug testing embodied in Dose Escalation that were suitable for traditional inert agents are now inadequate for these novel "living drugs". In the following, I propose an approach to escalating risk for patient exposures with these new immuno-gene therapy agents, termed Strategy Escalation, that accounts for the molecular and biological features of the modified cells and the methods of their administration. This proposal is offered not as a prescriptive but as a discussion framework that investigators may wish to consider in configuring their intended clinical applications.

  3. Intensity-Modulated Radiotherapy for Locally Advanced Non-Small-Cell Lung Cancer: A Dose-Escalation Planning Study

    International Nuclear Information System (INIS)

    Purpose: To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC). Methods and Materials: For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity). Results: IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p ≤.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD. Conclusion: In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT.

  4. Dose escalation for non-small cell lung cancer: Analysis and modelling of published literature

    International Nuclear Information System (INIS)

    Purpose: To review the published clinical data on non-small cell lung cancer treated with radical radiotherapy to confirm a dose-response relationship as a basis for further dose-escalation trials. Methods: Twenty-four published clinical trials were identified, 16 of which - with 29 different standard, hyper- and hypofractionated treatment schedules - were analysed. Prescription doses were converted to biologically-equivalent dose (BED), with a correction for repopulation. Disease-free survival data were corrected for the stage profile of each cohort to allow better comparison of results. We also analysed moderate (grade II and III) lung and oesophageal acute toxicity related to the corrected BED delivered to the tumour. Results: The clinical data analysed showed good agreement between the observed and modelled disease-free survival at 2 years when compared to the published models of Fenwick (correlation coefficient 0.525, p = 0.003) and Martel (correlation coefficient 0.492, p = 0.007), indicating a clear tumour dose-response. In the normally fractionated treatments (∼2 Gy per fraction), improved disease-free survival was generally observed in the shorter schedules (maximum around 6 weeks). However, the best outcomes were obtained for the hypofractionated schedules. No systematic relationship was seen between prescribed dose and lung or oesophageal acute toxicity, possibly due to dose selection depending on V20 or MLD in some studies and the diversity of the patients analysed. Conclusions: We have demonstrated a dose-response relationship for NSCLC based on clinical data. The clinical data provide a rational basis for selection of dose escalation schedules to be tested in future randomised trials.

  5. Dose escalation with stereotactic body radiation therapy boost for locally advanced non small cell lung cancer

    International Nuclear Information System (INIS)

    Low survival outcomes have been reported for the treatment of locally advanced non small cell lung cancer (LA-NSCLC) with the standard of care treatment of concurrent chemoradiation (cCRT). We present our experience of dose escalation using stereotactic body radiosurgery (SBRT) following conventional cCRT for patients with LA-NSCLC. Sixteen patients with a median age of 67.5 treated with fractionated SBRT from 2010 to 2012 were retrospectively analyzed. Nine (56%) of the patients had stage IIIB, 6 (38%) has stage IIIA, and 1 (6%) had recurrent disease. Majority of the patients (63%) presented with N2 disease. All patients had a PET CT for treatment planning. Patients received conventional cCRT to a median dose of 50.40 Gy (range 45–60) followed by an SBRT boost with an average dose of 25 Gy (range 20–30) given over 5 fractions. With a median follow-up of 14 months (range, 1–14 months), 1-year overall survival (OS), progression free survival (PFS), local control (LC), regional control (RC), and distant control (DC) rates were, 78%, 42%, 76%, 79%, and 71%, respectively. Median times to disease progression and regional failure were 10 months and 18 months, respectively. On univariate analysis, advanced age and nodal status were worse prognostic factors of PFS (p < 0.05). Four patients developed radiation pneumonitis and one developed hemoptysis. Treatment was interrupted in one patient who required hospitalization due to arrhythmias and pneumonia. Risk adaptive dose escalation with SBRT following external beam radiotherapy is possible and generally tolerated treatment option for patients with LA-NSCLC

  6. Cigarette smoking increases white blood cell aggregation in whole blood.

    OpenAIRE

    Bridges, A B; Hill, A; Belch, J J

    1993-01-01

    We studied the effect of chronic cigarette smoking on white blood cell aggregation, increased aggregation predisposes to microvascular occlusion and damage. Current smokers had significantly increased white blood cell aggregation when compared with non smokers. The presence of chronically activated white blood cells in current smokers may be relevant in the pathogenesis of ischaemic vascular disease.

  7. Strategies of dose escalation in the treatment of locally advanced non-small cell lung cancer: image guidance and beyond

    Directory of Open Access Journals (Sweden)

    Alexander eChi

    2014-06-01

    Full Text Available Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies. In this review, the limitations in target volume definition in previous studies; and the factors that may be critical to safe dose escalation in the treatment of locally advanced NSCLC, such as respiratory motion management, image guidance, intensity modulation, FDG-PET incorporation in the treatment planning process, and adaptive radiotherapy, are discussed. These factors, along with novel treatment approaches that have emerged in recent years, are proposed to warrant further investigation in future trials in a more comprehensive and integrated fashion.

  8. Cell-to-cell propagation of infectious cytosolic protein aggregates

    Science.gov (United States)

    Hofmann, Julia P.; Denner, Philip; Nussbaum-Krammer, Carmen; Kuhn, Peer-Hendrik; Suhre, Michael H.; Scheibel, Thomas; Lichtenthaler, Stefan F.; Schätzl, Hermann M.; Bano, Daniele; Vorberg, Ina M.

    2013-01-01

    Prions are self-templating protein conformers that replicate by recruitment and conversion of homotypic proteins into growing protein aggregates. Originally identified as causative agents of transmissible spongiform encephalopathies, increasing evidence now suggests that prion-like phenomena are more common in nature than previously anticipated. In contrast to fungal prions that replicate in the cytoplasm, propagation of mammalian prions derived from the precursor protein PrP is confined to the cell membrane or endocytic vesicles. Here we demonstrate that cytosolic protein aggregates can also behave as infectious entities in mammalian cells. When expressed in the mammalian cytosol, protein aggregates derived from the prion domain NM of yeast translation termination factor Sup35 persistently propagate and invade neighboring cells, thereby inducing a self-perpetuating aggregation state of NM. Cell contact is required for efficient infection. Aggregates can also be induced in primary astrocytes, neurons, and organotypic cultures, demonstrating that this phenomenon is not specific to immortalized cells. Our data have important implications for understanding prion-like phenomena of protein aggregates associated with human diseases and for the growing number of amyloidogenic proteins discovered in mammals. PMID:23509289

  9. Differential survival of solitary and aggregated bacterial cells promotes aggregate formation on leaf surfaces

    Science.gov (United States)

    Monier, J.-M.; Lindow, S. E.

    2003-01-01

    The survival of individual Pseudomonas syringae cells was determined on bean leaf surfaces maintained under humid conditions or periodically exposed to desiccation stress. Cells of P. syringae strain B728a harboring a GFP marker gene were visualized by epifluorescence microscopy, either directly in situ or after recovery from leaves, and dead cells were identified as those that were stained with propidium iodide in such populations. Under moist, conducive conditions on plants, the proportion of total live cells was always high, irrespective of their aggregated state. In contrast, the proportion of the total cells that remained alive on leaves that were periodically exposed to desiccation stress decreased through time and was only ≈15% after 5 days. However, the fraction of cells in large aggregates that were alive on such plants in both condition was much higher than more solitary cells. Immediately after inoculation, cells were randomly distributed over the leaf surface and no aggregates were observed. However, a very aggregated pattern of colonization was apparent within 7 days, and >90% of the living cells were located in aggregates of 100 cells or more. Our results strongly suggest that, although conducive conditions favor aggregate formation, such cells are much more capable of tolerating environmental stresses, and the preferential survival of cells in aggregates promotes a highly clustered spatial distribution of bacteria on leaf surfaces. PMID:14665692

  10. p53 Aggregates penetrate cells and induce the co-aggregation of intracellular p53.

    Directory of Open Access Journals (Sweden)

    Karolyn J Forget

    Full Text Available Prion diseases are unique pathologies in which the infectious particles are prions, a protein aggregate. The prion protein has many particular features, such as spontaneous aggregation, conformation transmission to other native PrP proteins and transmission from an individual to another. Protein aggregation is now frequently associated to many human diseases, for example Alzheimer's disease, Parkinson's disease or type 2 diabetes. A few proteins associated to these conformational diseases are part of a new category of proteins, called prionoids: proteins that share some, but not all, of the characteristics associated with prions. The p53 protein, a transcription factor that plays a major role in cancer, has recently been suggested to be a possible prionoid. The protein has been shown to accumulate in multiple cancer cell types, and its aggregation has also been reproduced in vitro by many independent groups. These observations suggest a role for p53 aggregates in cancer development. This study aims to test the «prion-like» features of p53. Our results show in vitro aggregation of the full length and N-terminally truncated protein (p53C, and penetration of these aggregates into cells. According to our findings, the aggregates enter cells using macropinocytosis, a non-specific pathway of entry. Lastly, we also show that once internalized by the cell, p53C aggregates can co-aggregate with endogenous p53 protein. Together, these findings suggest prion-like characteristics for p53 protein, based on the fact that p53 can spontaneously aggregate, these aggregates can penetrate cells and co-aggregate with cellular p53.

  11. Aggregation of Red Blood Cells: From Rouleaux to Clot Formation

    OpenAIRE

    Wagner, C.; Steffen, P.; Svetina, S

    2013-01-01

    Red blood cells are known to form aggregates in the form of rouleaux. This aggregation process is believed to be reversible, but there is still no full understanding on the binding mechanism. There are at least two competing models, based either on bridging or on depletion. We review recent experimental results on the single cell level and theoretical analyses of the depletion model and of the influence of the cell shape on the binding strength. Another important aggregation mechanism is caus...

  12. Tracking hypoxic signaling within encapsulated cell aggregates.

    Science.gov (United States)

    Skiles, Matthew L; Sahai, Suchit; Blanchette, James O

    2011-01-01

    , is therefore reduced and limited by diffusion. This reduced oxygen availability may especially impact β-cells whose insulin secretory function is highly dependent on oxygen. Capsule composition and geometry will also impact diffusion rates and lengths for oxygen. Therefore, we also describe a technique for identifying hypoxic cells within our PEG capsules. Infection of the cells with a recombinant adenovirus allows for a fluorescent signal to be produced when intracellular hypoxia-inducible factor (HIF) pathways are activated. As HIFs are the primary regulators of the transcriptional response to hypoxia, they represent an ideal target marker for detection of hypoxic signaling. This approach allows for easy and rapid detection of hypoxic cells. Briefly, the adenovirus has the sequence for a red fluorescent protein (Ds Red DR from Clontech) under the control of a hypoxia-responsive element (HRE) trimer. Stabilization of HIF-1 by low oxygen conditions will drive transcription of the fluorescent protein (Figure 1). Additional details on the construction of this virus have been published previously. The virus is stored in 10% glycerol at -80° C as many 150 μL aliquots in 1.5 mL centrifuge tubes at a concentration of 3.4 x 10(10) pfu/mL. Previous studies in our lab have shown that MIN6 cells encapsulated as aggregates maintain their viability throughout 4 weeks of culture in 20% oxygen. MIN6 aggregates cultured at 2 or 1% oxygen showed both signs of necrotic cells (still about 85-90% viable) by staining with ethidium bromide as well as morphological changes relative to cells in 20% oxygen. The smooth spherical shape of the aggregates displayed at 20% was lost and aggregates appeared more like disorganized groups of cells. While the low oxygen stress does not cause a pronounced drop in viability, it is clearly impacting MIN6 aggregation and function as measured by glucose-stimulated insulin secretion. Western blot analysis of encapsulated cells in 20% and 1% oxygen also

  13. Automatic analysis of microscopic images of red blood cell aggregates

    Science.gov (United States)

    Menichini, Pablo A.; Larese, Mónica G.; Riquelme, Bibiana D.

    2015-06-01

    Red blood cell aggregation is one of the most important factors in blood viscosity at stasis or at very low rates of flow. The basic structure of aggregates is a linear array of cell commonly termed as rouleaux. Enhanced or abnormal aggregation is seen in clinical conditions, such as diabetes and hypertension, producing alterations in the microcirculation, some of which can be analyzed through the characterization of aggregated cells. Frequently, image processing and analysis for the characterization of RBC aggregation were done manually or semi-automatically using interactive tools. We propose a system that processes images of RBC aggregation and automatically obtains the characterization and quantification of the different types of RBC aggregates. Present technique could be interesting to perform the adaptation as a routine used in hemorheological and Clinical Biochemistry Laboratories because this automatic method is rapid, efficient and economical, and at the same time independent of the user performing the analysis (repeatability of the analysis).

  14. Optimizing Collimator Margins for Isotoxically Dose-Escalated Conformal Radiation Therapy of Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: Isotoxic dose escalation schedules such as IDEAL-CRT [isotoxic dose escalation and acceleration in lung cancer chemoradiation therapy] (ISRCTN12155469) individualize doses prescribed to lung tumors, generating a fixed modeled risk of radiation pneumonitis. Because the beam penumbra is broadened in lung, the choice of collimator margin is an important element of the optimization of isotoxic conformal radiation therapy for lung cancer. Methods and Materials: Twelve patients with stage I-III non-small cell lung cancer (NSCLC) were replanned retrospectively using a range of collimator margins. For each plan, the prescribed dose was calculated according to the IDEAL-CRT isotoxic prescription method, and the absolute dose (D99) delivered to 99% of the planning target volume (PTV) was determined. Results: Reducing the multileaf collimator margin from the widely used 7 mm to a value of 2 mm produced gains of 2.1 to 15.6 Gy in absolute PTV D99, with a mean gain ± 1 standard error of the mean of 6.2 ± 1.1 Gy (2-sided P<.001). Conclusions: For NSCLC patients treated with conformal radiation therapy and an isotoxic dose prescription, absolute doses in the PTV may be increased by using smaller collimator margins, reductions in relative coverage being offset by increases in prescribed dose

  15. Harpin Mediates Cell Aggregation in Erwinia chrysanthemi 3937

    OpenAIRE

    Yap, Mee-Ngan; Rojas, Clemencia M.; Yang, Ching-Hong; Charkowski, Amy O.

    2006-01-01

    The hypersensitive response elicitor harpin (HrpN) of soft rot pathogen Erwinia chrysanthemi strains 3937 and EC16 is secreted via the type III secretion system and remains cell surface bound. Strain 3937 HrpN is essential for cell aggregation, but the C-terminal one-third of the protein is not required for aggregative activity.

  16. Macromolecular cell surface engineering for accelerated and reversible cellular aggregation.

    Science.gov (United States)

    Amaral, Adérito J R; Pasparakis, George

    2015-12-25

    We report the synthesis of two simple copolymers that induce rapid cell aggregation within minutes in a fully reversible manner. The polymers can act as self-supporting "cellular glues" or as "drivers" of 3D cell spheroids/aggregates formation at minute concentrations. PMID:26478926

  17. A planning study of radiotherapy dose escalation of PET-active tumour volumes in non-small cell lung cancer patients

    International Nuclear Information System (INIS)

    Background. Patients with non-small cell lung cancer (NSCLC) have poor prognosis partly because of high local failure rates. Escalating the dose to the tumour may decrease the local failure rates and thereby, improve overall survival, but the risk of complications will limit the possibility to dose-escalate a broad range of patients. Escalating only PET-active areas of the tumour may increase the potential for reaching high doses for a variety of tumour sizes and locations. Material and methods. Ten patients were randomly chosen for a dose escalation planning study. A planning target volume (PTV) was defined on the mid-ventilation scan of a four-dimensional computed tomography (4D-CT) scan and a boost planning target volume (PTV-boost) was defined based on a positron emission tomography computed tomography (PET-CT) scan. Treatment plans were created aiming to reach the highest achievable of 74 Gy, 78 Gy or 82 Gy in 2 Gy per fraction prescribed to the PTV-boost without compromising normal tissue constraints and with the PTV prescribed in all cases a biological equivalent dose in 2 Gy fractions of 66 Gy. Results. Nine of ten patients could be escalated to the highest dose level (82 Gy), while one patient was limited by the oesophagus dose constraint and could only reach 74 Gy. Four patients could be dose-escalated above 82 Gy without compromising normal tissue constraints. Conclusion. Dose-escalating only the PET-active areas of lung tumours to doses of 82 Gy while respecting normal tissue constraints is feasible, also in a series of unselected patients including cases with relatively large tumours

  18. Dose escalation in the radiotherapy of non-small-cell lung cancer with aperture-based intensity modulation and photon beam energy optimization for non-preselected patients

    International Nuclear Information System (INIS)

    Purpose: To verify the potential of aperture-based intensity-modulated radiotherapy (AB-IMRT) to realize dose escalation plans for non-preselected non-small-cell lung cancer (NSCLC) patients, using photon beam energy optimization. Methods and materials: Seven cases of NSCLC were retrospectively studied. Clinical reference plans were made at 60 Gy by an experienced dosimetrist. Dose escalation was applied to PTV2, a subvolume within the main PTV1. Escalation plans were optimized by considering beam angles (table and gantry), energy (6 and 23 MV) and weights, for an increasing dose to the PTV2, starting from 66 Gy and keeping 30 fractions. Results: In five cases, doses over 78 Gy could be achieved before exceeding organs at risk (OARs) standard tolerance. Peripheral overdosages, as well as lung and spinal cord tolerance doses, limited escalation. Means ± SD V95% parameters were (97.3 ± 0.9)% for PTV1s and (96.7 ± 2.2)% for PTV2s. Doses to OARs were also maintained at acceptable levels. Optimized plans made use of both low- and high-energy beams and had a similar number of monitor units compared to the 60 Gy clinical plans. Conclusions: The AB-IMRT system can successfully realize dose escalation for a sizeable number of cases. Plans produced contained few large segments, and are applicable to a wide range of tumor volumes and locations.

  19. Light scattering by aggregated red blood cells

    Science.gov (United States)

    Tsinopoulos, Stephanos V.; Sellountos, Euripides J.; Polyzos, Demosthenes

    2002-03-01

    In low flow rates, red blood cells (RBCs) fasten together along their axis of symmetry and form a so-called rouleaux. The scattering of He-Ne laser light by a rouleau consisting of n (2 less-than-or-equal n less-than-or-equal 8) average-sized RBCs is investigated. The interaction problem is treated numerically by means of an advanced axisymmetric boundary element--fast Fourier transform methodology. The scattering problem of one RBC was solved first, and the results showed that the influence of the RBC's membrane on the scattering patterns is negligible. Thus the rouleau is modeled as an axisymmetric, homogeneous, low-contrast dielectric cylinder, on the surface of which appears, owing to aggregated RBCs, a periodic roughness along the direction of symmetry. The direction of the incident laser light is considered to be perpendicular to the scatterer's axis of symmetry. The differential scattering cross sections in both perpendicular and parallel scattering planes and for all the scattering angles are calculated and presented in detail.

  20. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Jeffrey Y.C., E-mail: jwong@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Forman, Stephen; Somlo, George [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Rosenthal, Joseph [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Department of Pediatrics, City of Hope National Medical Center, Duarte, California (United States); Liu An; Schultheiss, Timothy; Radany, Eric [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Palmer, Joycelynne [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Stein, Anthony [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States)

    2013-01-01

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to

  1. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    International Nuclear Information System (INIS)

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days −10 to −6, etoposide (VP16) on Day −5 (60 mg/kg), and cyclophosphamide (CY) on Day −3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days −12 to −8 (800 μM min), TMI on Days −8 to −4, and VP16 on Day −3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible

  2. Effects of Dextran Molecular Weight on Red Blood Cell Aggregation

    OpenAIRE

    Neu, Björn; Wenby, Rosalinda; Meiselman, Herbert J.

    2008-01-01

    The reversible aggregation of human red blood cells (RBC) by proteins or polymers continues to be of biologic and biophysical interest, yet the mechanistic details governing the process are still being explored. Although a depletion model with osmotic attractive forces due to polymer depletion near the RBC surface has been proposed for aggregation by the neutral polyglucose dextran, its applicability at high molecular mass has not been established. In this study, RBC aggregation was measured ...

  3. On the height of cell aggregates formed with positive dielectrophoresis

    International Nuclear Information System (INIS)

    The influence of a number of parameters on the height of cell aggregates formed by positive dielectrophoresis was systematically investigated. It was found that the aggregate height could be increased by following a number of simple rules. Interdigitated electrodes with oppositely placed castellations gave higher aggregate heights than interdigitated parallel electrodes. The optimal frequency was identified to be 1 MHz. To obtain the highest aggregates, the conductivity of the suspending medium should be kept to the lowest value obtainable, as should the fluid flow rate through the chamber. Aggregate height increased with increasing voltage, but the effect of increasing the voltage diminished as higher aggregate heights were reached. Optima were observed in the aggregate height as a function of the electrode characteristic size, which depended on the cell type and cell size. It was shown to be possible to create aggregate heights of over 150 μm for all the three cell types (bacteria, yeasts and mammalian cells) employed, using voltages of only 20 Vpk-pk

  4. Prevention and dispersion of contrast media induced red cell aggregates

    International Nuclear Information System (INIS)

    Red cell aggregation was observed microscopically when human blood and contrast media were mixed on glass slides. Aggregation was more frequent in low-osmolal media: mainly rouleaux were formed in ioxaglate but irregular aggregates in non-ionic media. Aggregation was similar at concentrations of 150 and 300 mg I/ml. Pre-treatment of glass slides with heparinized saline reduced red cell aggregation but saline was almost as effective. Most of the irregular aggregates dispersed when saline or heparinized saline was applied to them. Saline and heparinized saline had an identical dispersing effect. After incubation of the aggregates in iopamidol in plastic tubes for one or five minutes, saline was injected into the tubes, and after mixing the solution was poured onto glass slides and examined under the microscope. Only a few small irregular aggregates were detected in 6/60 specimens. It is concluded that ionicity of a flushing medium and shear of the injection are able to disperse red cell aggregates during angiography. (orig.)

  5. Phase 1 Study of Dose Escalation in Hypofractionated Proton Beam Therapy for Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gillin, Michael [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wei, Caimiao [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H.; Swanick, Cameron; Alvarado, Tina; Komaki, Ritsuko; Cox, James D.; Chang, Joe Y. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2013-07-15

    Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.

  6. Phase 1 Study of Dose Escalation in Hypofractionated Proton Beam Therapy for Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC

  7. Capillary hydrodynamic chromatography reveals temporal profiles of cell aggregates.

    Science.gov (United States)

    Tang, Ya-Ru; Huang, Hsin-Yi; Hu, Jie-Bi; Rattinam, Rajesh; Li, Chun-Hsien; Chen, Yu-Chie; Urban, Pawel L

    2016-03-01

    Microbial cells are known to form aggregates. Such aggregates can be found in various matrices; for example, functional drinks. Capillary hydrodynamic chromatography (HDC) enables separation of particles by size using nanoliter-scale volumes of samples. Here we propose an approach based on HDC for characterisation of real samples containing aggregated and non-aggregated bacterial and fungal cells. Separation of cells and cell aggregates in HDC arises from the parabolic flow profile under laminar flow conditions. In the presented protocol, hydrodynamic separation is coupled with different on-line and off-line detectors (light absorption/scattering and microscopy). The method has successfully been applied in the monitoring of dynamic changes in the microbiome of probiotic drinks. Chromatographic profiles of yogurt and kefir samples obtained at different times during fermentation are in a good agreement with microscopic images. Moreover, thanks to the implementation of an area imaging detector, capillary HDC could be multiplexed and used to profile spatial gradients in cell suspensions, which arise in the course of sedimentation of cells and cell aggregates. This result shows compatibility of sedimentation analysis and capillary HDC. We believe that the approach may find applications in the profiling of functional foods and other matrices containing aggregated bioparticles. PMID:26873471

  8. Energy Consumption of Escalators

    OpenAIRE

    Uimonen, Semen

    2015-01-01

    This thesis studies the impact of passenger load and different load scenarios on the energy consumption of escalators. The scope of thesis is analysis of energy used, in kWh, by an escalator pair with specific technical requirements, and effect of the passenger flow on energy consumption of the selected escalator pair. Previous studies revealed lack of knowledge about the effects of power saving modes on the power consumption profiles of escalators. This study provides typical daily energy co...

  9. Aggregation of Red Blood Cells: From Rouleaux to Clot Formation

    CERN Document Server

    Wagner, C; Svetina, S

    2013-01-01

    Red blood cells are known to form aggregates in the form of rouleaux. This aggregation process is believed to be reversible, but there is still no full understanding on the binding mechanism. There are at least two competing models, based either on bridging or on depletion. We review recent experimental results on the single cell level and theoretical analyses of the depletion model and of the influence of the cell shape on the binding strength. Another important aggregation mechanism is caused by activation of platelets. This leads to clot formation which is life saving in the case of wound healing but also a major cause of death in the case of a thrombus induced stroke. We review historical and recent results on the participation of red blood cells in clot formation.

  10. Aggregation of red blood cells: From rouleaux to clot formation

    Science.gov (United States)

    Wagner, Christian; Steffen, Patrick; Svetina, Saša

    2013-06-01

    Red blood cells are known to form aggregates in the form of rouleaux. This aggregation process is believed to be reversible, but there is still no full understanding on the adhesion mechanism. There are at least two competing models, based either on bridging or on depletion. We review recent experimental results on the single cell level and theoretical analyses of the depletion model and of the influence of the cell shape on the adhesion strength. Another important aggregation mechanism is caused by activation of platelets. This leads to clot formation which is life-saving in the case of wound healing, but also a major cause of death in the case of a thrombus induced stroke. We review historical and recent results on the participation of red blood cells in clot formation.

  11. Effect of Particle Size in Aggregates of ZnO-Aggregate-Based Dye-Sensitized Solar Cells

    International Nuclear Information System (INIS)

    Graphical abstract: The crystal size in submicrometer ZnO aggregates plays an important role in the ZnO-aggregate-based dye-sensitized solar cells. Optimal crystal size in aggregates leads to balance parameters of dye absorption, electron diffusion between crystals and recombination to get higher light-to-electricity conversion efficiency. - Highlights: • A new method is developed for controlling crystal size in ZnO aggregate. • Dye adsorption, electron diffusion and recombination depend on crystal size in the aggregates. • 20-30 nm crystal size in aggregates can optimize these factors to achieve higher efficiency of DSC. - Abstract: Effect of particle size in aggregates on ZnO-aggregate-based dye-sensitized solar cells is investigated. A two-step hydrothermal method is developed for preparing submicrometer ZnO aggregates with different crystal sizes via controlling regrowth temperature. Three groups of ZnO-aggregate-based dye-sensitized solar cells with the different crystal sizes in the aggregates are fabricated for comparison of the photovoltaic properties. The results indicate that the cell made of crystal size of 25-30 nm has the highest light-to-electricity conversion efficiency of 4.54% for the dye-sensitized solar cells. According to the analysis of absorption spectra, dark current curves, photoelectron decay and electrochemical impedance spectra, we find that the aggregates with smaller crystal size have higher capability of dye adsorption, while the aggregates with larger crystal size have faster electron diffusion, and less recombination. Therefore, optimal crystal size in the aggregates for photoanode leads to balance these parameters to get higher light-to-electricity conversion efficiency. This investigation is important to the improvement of conversion efficiency for dye-sensitized solar cells

  12. A microwell cell culture platform for the aggregation of pancreatic β-cells.

    Science.gov (United States)

    Bernard, Abigail B; Lin, Chien-Chi; Anseth, Kristi S

    2012-08-01

    Cell-cell contact between pancreatic β-cells is important for maintaining survival and normal insulin secretion. Various techniques have been developed to promote cell-cell contact between β-cells, but a simple yet robust method that affords precise control over three-dimensional (3D) β-cell cluster size has not been demonstrated. To address this need, we developed a poly(ethylene glycol) (PEG) hydrogel microwell platform using photolithography. This microwell cell-culture platform promotes the formation of 3D β-cell aggregates of defined sizes from 25 to 210 μm in diameter. Using this platform, mouse insulinoma 6 (MIN6) β-cells formed aggregates with cell-cell adherin junctions. These naturally formed cell aggregates with controllable sizes can be removed from the microwells for macroencapsulation, implantation, or other biological assays. When removed and subsequently encapsulated in PEG hydrogels, the aggregated cell clusters demonstrated improved cellular viability (>90%) over 7 days in culture, while the β-cells encapsulated as single cells maintained only 20% viability. Aggregated MIN6 cells also exhibited more than fourfold higher insulin secretion in response to a glucose challenge compared with encapsulated single β-cells. Further, the cell aggregates stained positively for E-cadherin, indicative of the formation of cell junctions. Using this hydrogel microwell cell-culture method, viable and functional β-cell aggregates of specific sizes were created, providing a platform from which other biologically relevant questions may be answered. PMID:22320435

  13. Hemoglobin Aggregation in Single Red Blood Cells of Sickle Cell Anemia

    Science.gov (United States)

    Nishio, Izumi; Tanaka, Toyoichi; Sun, Shao-Tang; Imanishi, Yuri; Tsuyoshi Ohnishi, S.

    1983-06-01

    A laser light scattering technique was used to observe the extent of hemoglobin aggregation in solitary red blood cells of sickle cell anemia. Hemoglobin aggregation was confirmed in deoxygenated cells. The light scattering technique can also be applied to cytoplasmic studies of any biological cell.

  14. E4 - Energy efficient elevators and escalators. Elevators and escalators in Germany from an energy perspective

    Energy Technology Data Exchange (ETDEWEB)

    Hirzel, Simon; Fleiter, Tobias; Rosende, Daniel

    2010-01-31

    This report aims to provide a brief introduction to the German elevator and escalator market, and gives an aggregated view of current and future developments focusing on energy consumption and energy-related emissions. This update report of January 2010 is an extended version of a report published in April 2009 before the final results from a monitoring campaign carried out within the project were available. During this campaign, 81 installations (74 elevators and 7 escalators) were monitored in terms of energy consumption. In the first section, the structure of the installed German elevator and escalator capacity is presented. The estimates1 were provided courtesy of the two main associations representing elevators and escalators in Germany: the VDMA (Verband Deutscher Maschinen- und Anlagenbau - German Engineering Federation) and the VFA-Interlift e.V. -Verband fuer Aufzugstechnik (Association for Lift Technology). This section is followed by a short description of the German construction sector and its implications for elevators and escalators. The third section describes German electricity production in terms of its environmental impact with the main focus on the carbon dioxide emissions of the national power plants. Then the energy consumption of elevators and escalators in Germany is analyzed, comparing the results to total energy production in Germany.2 The final section summarizes the different aspects and derives indications about the future development of the total energy consumption of elevators and escalators in Germany. (orig.)

  15. Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial

    Energy Technology Data Exchange (ETDEWEB)

    Westover, Kenneth D. [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Loo, Billy W. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Gerber, David E. [Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Iyengar, Puneeth; Choy, Hak [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Diehn, Maximilian [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Hughes, Randy; Schiller, Joan; Dowell, Jonathan [Division of Hematology-Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wardak, Zabi [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Sher, David [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Christie, Alana; Xie, Xian-Jin [Department of Clinical Science, Southwestern Medical Center, Dallas, Texas (United States); Corona, Irma [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Sharma, Akanksha [School of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Wadsworth, Margaret E. [Radiation Oncology of Mississippi, Jackson, Mississippi (United States); Timmerman, Robert, E-mail: Robert.Timmerman@utsouthwestern.edu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States)

    2015-09-01

    Purpose: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Methods and Materials: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. Results: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P=.24). The median overall survival was 6 months with no significant differences between dose levels (P=.59). Conclusions: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long

  16. Influence of dose calculation algorithms on isotoxic dose-escalation of non-small cell lung cancer radiotherapy

    International Nuclear Information System (INIS)

    Background and purpose: A series of phase I/II clinical trials are being initiated in several UK centres to explore the use of dose-escalated schedules for the treatment of non-small cell lung cancer (NSCLC). Among them the IDEAL-CRT trial (ISRCTN12155469) will investigate the introduction of individualised 'isotoxic' treatment schedules based on the relative mean lung normalised total dose (rNTDmean), an estimator related to lung toxicity. Since treatment planning will be performed using different treatment planning systems (TPSs), for the quality assurance of the trial we have carried out work to quantify the influence of dose calculation algorithms based on the determination of rNTDmean and on the choice of individualised prescription doses. Material and methods: Twenty-five patient plans with stage I, II and III NSCLC were calculated, with the same prescription dose, using the Adaptive Convolve (AC) and Collapsed Cone (CC) algorithms of the Pinnacle TPS, the pencil beam convolution (PBC) and AAA algorithms of Eclipse, and the CC and pencil beam (PB) algorithms of Oncentra Masterplan (OMP). For the paired-lungs-GTV structure, dose-volume histograms were obtained and used to calculate the corresponding rNTDmean values and results obtained with the different algorithms were compared. Results: For most (19 out of 25) of the patients studied, no algorithm-to-algorithm differences were seen in dose prescription based on rNTDmean. For the other 6 patients differences were within 2.3 Gy, except in one case where the difference was 4 Gy. Conclusions: For the IDEAL-CRT trial no corrections need to be applied to the value of rNTDmean calculated using any of the more advanced convolution/superposition algorithms studied in this work. For the two pencil beam algorithms analysed, no correction is necessary for the data obtained with the Eclipse-PBC, while for OMP-PB data a small correction needs to be applied, by using a scaling factor, to make prescription doses consistent

  17. Precision Hypofractionated Radiation Therapy in Poor Performing Patients With Non-Small Cell Lung Cancer: Phase 1 Dose Escalation Trial

    International Nuclear Information System (INIS)

    Purpose: Treatment regimens for locally advanced non-small cell lung cancer (NSCLC) give suboptimal clinical outcomes. Technological advancements such as radiation therapy, the backbone of most treatment regimens, may enable more potent and effective therapies. The objective of this study was to escalate radiation therapy to a tumoricidal hypofractionated dose without exceeding the maximally tolerated dose (MTD) in patients with locally advanced NSCLC. Methods and Materials: Patients with stage II to IV or recurrent NSCLC and Eastern Cooperative Oncology Group performance status of 2 or greater and not candidates for surgical resection, stereotactic radiation, or concurrent chemoradiation were eligible. Highly conformal radiation therapy was given to treat intrathoracic disease in 15 fractions to a total of 50, 55, or 60 Gy. Results: Fifty-five patients were enrolled: 15 at the 50-Gy, 21 at the 55-Gy, and 19 at the 60-Gy dose levels. A 90-day follow-up was completed in each group without exceeding the MTD. With a median follow-up of 12.5 months, there were 93 grade ≥3 adverse events (AEs), including 39 deaths, although most AEs were considered related to factors other than radiation therapy. One patient from the 55- and 60-Gy dose groups developed grade ≥3 esophagitis, and 5, 4, and 4 patients in the respective dose groups experienced grade ≥3 dyspnea, but only 2 of these AEs were considered likely related to therapy. There was no association between fraction size and toxicity (P=.24). The median overall survival was 6 months with no significant differences between dose levels (P=.59). Conclusions: Precision hypofractionated radiation therapy consisting of 60 Gy in 15 fractions for locally advanced NSCLC is generally well tolerated. This treatment regimen could provide patients with poor performance status a potent alternative to chemoradiation. This study has implications for the cost effectiveness of lung cancer therapy. Additional studies of long

  18. Mesenchymal Stem Cell (MSC) Aggregate Formation in vivo

    Science.gov (United States)

    Bartosh, Thomas J.; Ylostalo, Joni H.

    2016-01-01

    Human mesenchymal stem/progenitor cells (MSCs) isolated from various adult tissues show remarkable therapeutic potential and are being employed in clinical trials for the treatment of numerous diseases (Prockop et al., 2010). While routes of cell administration vary, profound beneficial effects of MSCs in animal models have been observed following intraperitoneal injections of the cells (Roddy et al., 2011). Similar to MSC spheres formed in culture under conditions where attachment to plastic is not permitted (Bartosh et al., 2010), MSCs injected into the peritoneum of mice spontaneously aggregate into 3D sphere-like structures (Bartosh et al., 2013). During the process of sphere assembly and compaction, MSCs upregulate expression of numerous therapeutic anti-inflammatory and immune modulatory factors. Here we describe the method we previously used for the generation of human bone marrow-derived MSC aggregates/spheres in vivo (Bartosh et al., 2013). By tagging the MSCs with green fluorescent protein (GFP), the aggregates formed can be easily visualized, collected and analyzed for changes in cellular properties and interactions with host immune cells.

  19. CCN2/CTGF silencing blocks cell aggregation in embryonal carcinoma P19 cell

    Directory of Open Access Journals (Sweden)

    D.P. Aguiar

    2011-03-01

    Full Text Available Connective tissue growth factor (CCN2/CTGF is a matricellular-secreted protein involved in extracellular matrix remodeling. The P19 cell line is an embryonic carcinoma line widely used as a cellular model for differentiation and migration studies. In the present study, we employed an exogenous source of CCN2 and small interference RNA to address the role of CCN2 in the P19 cell aggregation phenomenon. Our data showed that increasing CCN2 protein concentrations from 0.1 to 20 nM decreased the number of cell clusters and dramatically increased cluster size without changing proliferation or cell survival, suggesting that CCN2 induced aggregation. In addition, CCN2 specific silencing inhibited typical P19 cell aggregation, which could be partially rescued by 20 nM CCN2. The present study demonstrates that CCN2 is a key molecule for cell aggregation of embryonic P19 cells.

  20. Photoacoustic assessment of oxygen saturation: effect of red blood cell aggregation

    Science.gov (United States)

    Hysi, Eno; Saha, Ratan K.; Kolios, Michael C.

    2013-03-01

    The simultaneous photoacoustic assessment of oxygen saturation and red blood cell aggregation is presented. Aggregation was induced on porcine red blood cells using Dextran-70 at multiple hematocrit levels. Samples were exposed to 750 nm and 1064 nm for each hematocrit and aggregate size in order to compute the oxygen saturation. As the size of the aggregate increased, the photoacoustic signal amplitude increased monotonically. The same trend was observed for increasing hematocrit at each aggregation level. The oxygen saturation of aggregated samples was 30% higher than non-aggregated samples at each hematocrit level. This suggests that the presence of red blood cell aggregates impairs the release of oxygen to the surrounding environment. Such a result has important implications for detecting red blood cell aggregation non-invasively and making clinical decisions based on the simulatenous assessment of oxygen saturation.

  1. Aggregation patterns of fetal rat brain cells following exposure to X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Shoji, R.; Suzuki, K.; Lee, I.P.

    1980-01-01

    In our search for a simplified in vitro test system to assess the teratogenic effects of physical factors, we studied the effects of total maternal body X-irradiation on aggregation patterns of enzymatically isolated fetal rat brain cells and on ultrastructural aggregate changes. The fetal brain cells were derived from day 14 gestation fetuses of pregnant Sprague-Dawley (CD strain) rats exposed to X-irradiation (25 - 200 R) one hour prior to sacrifice. Notable changes in the cell aggregates following X-irradiation included a reduction in cell aggregate size and an increase in number. The frequency of cell aggregates was higher in the treated than in the control group, and the mean diameter of cell aggregates was inversely related to increasing X-irradiation doses. Transmission electron microscopy revealed in isolated cells features of degenerative process which were similar to those found in intact fetal brain lesions caused by maternal X-irradiation. Furthermore, scanning electron microscopy revealed that inhibition of cell aggregation following X-irradiation could probably be attributed to inhibition of membrane filopodia development and a consequent failure of cell aggregates to fuse into a greater cell aggregate mass. These results suggest that the membrane factors which influence cell aggregation may be a useful parameter to assess early effects of X-irradiation-induced brain deformity. Presently, the cell aggregation culture system is being further evaluated as a short term test system for environmental teratogens.

  2. Cell-to-cell propagation of infectious cytosolic protein aggregates

    OpenAIRE

    Hofmann, Julia P.; Denner, Philip; Nussbaum-Krammer, Carmen; Kuhn, Peer-Hendrik; Suhre, Michael H.; Scheibel, Thomas; Lichtenthaler, Stefan F; Schätzl, Hermann M; Bano, Daniele; Vorberg, Ina M.

    2013-01-01

    Prions are self-templating protein conformers that replicate by recruitment and conversion of homotypic proteins into growing protein aggregates. Originally identified as causative agents of transmissible spongiform encephalopathies, increasing evidence now suggests that prion-like phenomena are more common in nature than previously anticipated. In contrast to fungal prions that replicate in the cytoplasm, propagation of mammalian prions derived from the precursor protein PrP is confined to t...

  3. Effect of Thai medicinal plant extracts on cell aggregation of Escherichia coli O157: H7.

    OpenAIRE

    Limsuwan, S.; Vanmanee, S.; Voravuthikunchai, S.

    2005-01-01

    Medicinal plants have been used for treating diarrhoea but the interference mechanisms are not clearly understood. One possible hypothesis is that of an effect on cell surface hydrophobicity of microbial cells. In this study, we examined cell aggregation affected by crude extracts of Thai medicinal plants on cell surface hydrophobicity of Escherichia coli strains by salt aggregation test. Correlation between minimal inhibitory concentration and cell aggregation was performed. Aqueous and etha...

  4. Coagulation, red cell aggregation, and the nonionic contrast agents

    International Nuclear Information System (INIS)

    Interest in the interactions between iodinated contrast agents and blood has been renewed recently following reports by Robertson in the United States of clots forming in blood-contaminated nonionic contrast agents in syringes, and by Raininko and Ylinen in Sweden of disordered red cell aggregation seemingly stimulated by nonionic contrast agents. These phenomena have been described and explained, and their significance for clinical angiography have been discussed. It has been suggested by a number of commentators that some contrast agents may be actively prothrombotic

  5. Enhancement of Chemotactic Cell Aggregation by Haptotactic Cell-To-Cell Interaction.

    Directory of Open Access Journals (Sweden)

    Tae-Goo Kwon

    Full Text Available The crawling of biological cell is a complex phenomenon involving various biochemical and mechanical processes. Some of these processes are intrinsic to individual cells, while others pertain to cell-to-cell interactions and to their responses to extrinsically imposed cues. Here, we report an interesting aggregation dynamics of mathematical model cells, when they perform chemotaxis in response to an externally imposed global chemical gradient while they influence each other through a haptotaxis-mediated social interaction, which confers intriguing trail patterns. In the absence of the cell-to-cell interaction, the equilibrium population density profile fits well to that of a simple Keller-Segal population dynamic model, in which a chemotactic current density [Formula: see text] competes with a normal diffusive current density [Formula: see text], where p and ρ refer to the concentration of chemoattractant and population density, respectively. We find that the cell-to-cell interaction confers a far more compact aggregation resulting in a much higher peak equilibrium cell density. The mathematical model system is applicable to many biological systems such as swarming microglia and neutrophils or accumulating ants towards a localized food source.

  6. Noradrenergic system in cultured aggregates of fetal rat brain cells: morphology of the aggregates and pharmacological indices of noradrenergic neurons

    Energy Technology Data Exchange (ETDEWEB)

    Majocha, R.E.; Pearse, R.N.; Baldessarini, R.J.; Delong, G.R.; Walton, K.G. (Harvard Medical School, Boston, MA (USA))

    1981-12-28

    Spherical aggregates formed rapidly in culture by re-aggregation of trypsin-dissociated brain cells from the 17-day-old fetal rat. Over about 10 days an initially random distribution of cells evolved into a 3-layered arrangement; cells with characteristics of neurons were found largely in the intermediate layer. The survival of neuronal and glial cell types was evaluated histologically and verified by electron microscopy, which revealed synaptic and myelin structures that rapidly increased in number after 18 days in culture. Levels of norepinephrine (NE) and dopamine (DA) reached peaks of 9.5 and 4.4 ng/mg protein, respectively, at culture day 21. Uptake of (/sup 3/H)NE paralleled these amine levels and was blocked by desipramine or pretreatment with either reserpine or 6-OH-DA. Autoradiographs of aggregates labeled with (/sup 3/H)NE showed a high density of silver grains over cells, apparently neurons, with branching processes traced for 120 ..mu..m. Previously accumulated (/sup 3/H)NE was released under depolarizing conditions (high (K/sup +/) or vertridine) only in the presence of Ca/sup 2 +/. Release was induced to a lesser extent by kainic > glutamic acid. Thus, such aggregates appear to contain catecholaminergic neurons capable of synthesis, uptake and release of NE. The time course of development of these functions supports suggestions that aggregate preparations might be useful in studying neurochemical or morphological aspects of brain development and function in vitro.

  7. Enhancement of red blood cell aggregation by plasma triglycerides.

    Science.gov (United States)

    Cicha, I; Suzuki, Y; Tateishi, N; Maeda, N

    2001-01-01

    The effects of plasma triglycerides level on human red blood cells (RBCs) indices, hematological parameters, RBCs aggregation velocity and whole blood viscosity were studied at 2 hours after high-fat or low-fat meal. Proteins, triglycerides and cholesterol levels of plasma were analysed. The RBCs rouleaux formation rate was measured in 70% autologous plasma (with 30% phosphate-buffered saline, PBS) or 1 g/dl dextran T70 solution (with 4 g/dl bovine serum albumin) in PBS, using a low-shear rheoscope. The results were grouped according to triglycerides content in plasma. No significant difference in whole blood viscosity, hematological parameters, RBC indices, protein and cholesterol content was observed between high-fat and low-fat blood samples. There was a significant increase in rouleaux formation rate of samples with high triglyceride levels, when measured in 70% autologous plasma, but it was not significant in dextran T70 containing medium. In conclusion, the results obtained suggest that alteration of plasma lipid levels as well as possible changes in the cell membrane lipid composition lead to enhanced RBC aggregation. PMID:11564913

  8. A population balance equation model of aggregation dynamics in Taxus suspension cell cultures.

    Science.gov (United States)

    Kolewe, Martin E; Roberts, Susan C; Henson, Michael A

    2012-02-01

    The nature of plant cells to grow as multicellular aggregates in suspension culture has profound effects on bioprocess performance. Recent advances in the measurement of plant cell aggregate size allow for routine process monitoring of this property. We have exploited this capability to develop a conceptual model to describe changes in the aggregate size distribution that are observed over the course of a Taxus cell suspension batch culture. We utilized the population balance equation framework to describe plant cell aggregates as a particulate system, accounting for the relevant phenomenological processes underlying aggregation, such as growth and breakage. We compared model predictions to experimental data to select appropriate kernel functions, and found that larger aggregates had a higher breakage rate, biomass was partitioned asymmetrically following a breakage event, and aggregates grew exponentially. Our model was then validated against several datasets with different initial aggregate size distributions and was able to quantitatively predict changes in total biomass and mean aggregate size, as well as actual size distributions. We proposed a breakage mechanism where a fraction of biomass was lost upon each breakage event, and demonstrated that even though smaller aggregates have been shown to produce more paclitaxel, an optimum breakage rate was predicted for maximum paclitaxel accumulation. We believe this is the first model to use a segregated, corpuscular approach to describe changes in the size distribution of plant cell aggregates, and represents an important first step in the design of rational strategies to control aggregation and optimize process performance. PMID:21910121

  9. Evaluation of red blood cell aggregation in diabetes by computerized image analysis.

    Science.gov (United States)

    Foresto, P; D'Arrigo, M; Carreras, L; Cuezzo, R E; Valverde, J; Rasia, R

    2000-01-01

    Red blood cell (RBC) aggregation has been widely studied and its importance is well established in the rheology of microcirculation. RBC aggregation is a major factor responsible for the flow properties of blood. Increased RBC aggregation has been observed in several pathological states. Therefore, the measurement of erythrocyte aggregation is rheologically important for quantifying flow abnormality in pathological conditions. Normal RBC under low flow or at rest form rouleaux aggregates, while abnormal RBC aggregation may lead to the formation of irregular aggregate structures, which may be induced by cell-associated factors (reduced membrane sialic acid levels) but also by extracellular factors. The main objective of the present investigation was to study RBC aggregate morphology in diabetic patients, using direct microscopic observation and numerical processing of recorded digitized images. Blood samples were obtained from 20 diabetic patients and from 15 normal control subjects. The aggregate morphology was quantified by the so-called Aggregate Shape Parameter (ASP) defined as the ratio of the aggregate projected area to its square perimeter. ASP appeared significantly higher (p rouleaux aggregates provides a useful reference for measuring deviations of RBC aggregate morphology. Increased aggregation of RBC resulting from a decreased sialylation of glycophorins may be an important factor in the development of vascular diseases and in the microcirculation impairment. PMID:11188894

  10. Beta-adrenoceptor antagonists enhance white blood cell aggregation in patients with ischaemic heart disease.

    OpenAIRE

    Bridges, A B; Pringle, T. H.; McNeill, G P; Tavendale, R; Belch, J J

    1992-01-01

    The effects of beta-adrenoceptor antagonists, calcium channel blockers and long acting nitrates on white blood cell (WBC) aggregation were studied in patients with ischaemic heart disease. WBC aggregation was significantly increased by beta-adrenoceptor antagonists (P = 0.011) but was unaffected by either calcium channel blockers or long acting nitrates. Enhanced WBC aggregation promotes microvascular occlusion and damage.

  11. Wavelength selection in measuring red blood cell aggregation based on light transmittance

    OpenAIRE

    Uyuklu, Mehmet; Canpolat, Murat; Meiselman, Herbert J.; Baskurt, Oguz K.

    2011-01-01

    The reversible aggregation of red blood cells (RBC) is of current basic science and clinical interest. Using a flow channel and light transmittance (LT) through RBC suspensions, we have examined the effects of wavelength (500 to 900 nm) on the static and dynamic aspects of RBC aggregation for normal blood and suspensions with reduced or enhanced aggregation; the effects of oxygenation were also explored. Salient observations include: 1. significant effects of wavelength on aggregation paramet...

  12. Erythrocyte deformability and aggregation in homozygous sickle cell disease.

    Science.gov (United States)

    Vayá, Amparo; Collado, Susana; Dasí, Maria Angeles; Pérez, Maria Luz; Hernandez, Jose Luis; Barragán, Eva

    2014-01-01

    Rheological properties of homozygous sickle cell anaemia (SCA) show marked heterogeneity, which may be explained in part by the concomitance of alpha genotypes or beta haplotypes, along with hydroxurea (HU) treatment. To further clarify this issue, in 11 homozygous patients with SCA in the steady state and in 16 healthy controls, we analysed erythrocyte deformability (ED) in a Rheodyn SSD by means of the Elongation Index (EI) at 12, 30 and 60 Pa, and erythrocyte aggregation at stasis (EA0) and at 3 sec-1 (EA1) in a Myrenne aggregometer along with fibrinogen, biochemical and haematological parameters. When compared with controls, homozygous (SS) patients showed a lower EI at all the shear stresses tested (p < 0.01) and higher EA0 (p < 0.014), but not higher EA1 (p = 0.076). Fibrinogen did not show statistical differences (p = 0.642). In the Spearman's correlation IE60 correlated inversely with Hb S (p < 0.05) and directly with MCV, MCH and Hb F levels (p < 0.01). EA0 correlated inversely with MCV, MCH, Hb F (p < 0.01) and directly with Hb S (p < 0.05). HU treatment improved EI and EA0, but not EA1. This paradoxical behaviour of HU on erythrocyte aggregation merits further research to be clarified. PMID:23603322

  13. Correlation of Red Blood Cell Aggregate Size with Transmitted Light Intensity Distributions

    Science.gov (United States)

    Hitt, Darren L.

    1998-11-01

    Under sufficiently low shear rates, such as those encountered in the microcirculation, human red blood cells are known to form aggregate structures (`rouleaux'). These aggregates may range in size from a simple chain containing only a few cells to complex three-dimensional structures containing tens of cells. Previous studies have attempted to characterize the aggregate size by examining the spatial distribution of transmitted light intensity resulting from transillumination of the blood flow. For experiments performed in vitro and in vivo, spectral analysis of the transmitted light intensities has shown that the presence of aggregates in the flow can linked with an increase in the spectral power at small wavenumbers. The magnitudes of the affected wavenumbers correspond to structures considerably larger than individual cells. A precise numerical correlation, however, is difficult to establish. In this work, computer simulations of aggregating blood flow are used along with statistical considerations in an attempt to better correlate the observed spectral trends with actual aggregate size.

  14. Effect of ionic and non-ionic contrast media on red cell aggregation in vitro

    International Nuclear Information System (INIS)

    The effect of solutions of the ionic contrast media diatrizoate, iocarmate, and metrizoate and the non-ionic metrizamide on red cell aggregation in vitro was examined. The aggregation was recorded by both microphotography and photometry in a counter-rotating rheoscope chamber. All the contrast media decreased the formation of red cell aggregates. This desaggregating ability increased with both increasing volume ratio (contrast media/blood) and with increasing osmolality of the contrast media. The desaggregating effect was also obtained with the contrast media solutions isotonic with blood. The iocarmate and diatrizoate solutions induced less reduction in red cell aggregation than the metrizoate and metrizamide solutions. (Auth.)

  15. Recombinant T-Cell Receptor Ligand (RTL for Treatment of Multiple Sclerosis: A Double-Blind, Placebo-Controlled, Phase 1, Dose-Escalation Study

    Directory of Open Access Journals (Sweden)

    Vijayshree Yadav

    2012-01-01

    Full Text Available Background. Recombinant T-cell receptor ligand 1000 (RTL1000 is a single-chain protein construct containing the outer two domains of HLA-DR2 linked to myelin-oligodendrocyte-glycoprotein- (MOG- 35–55 peptide. Analogues of RTL1000 induce T-cell tolerance, reverse clinical and histological disease, and promote repair in experimental autoimmune encephalomyelitis (EAE in DR2 transgenic, C57BL/6, and SJL/J mice. Objective. Determining the maximum tolerated dose, safety, and tolerability of RTL1000 in multiple sclerosis (MS subjects. Methods. This was a multicenter, Phase I dose-escalation study in HLA-DR2+ MS subjects. Consecutive cohorts received RTL1000 doses of 2, 6, 20, 60, 200, and 100 mg, respectively. Subjects within each cohort randomly received a single intravenous infusion of RTL1000 or placebo at a 4 : 2 ratio. Safety monitoring included clinical, laboratory, and brain magnetic resonance imaging (MRI evaluations. Results. Thirty-four subjects completed the protocol. All subjects tolerated the 2–60 mg doses of RTL1000. Doses ≥100 mg caused hypotension and diarrhea in 3 of 4 subjects, leading to discontinuation of further enrollment. Conclusions. The maximum tolerated dose of RTL1000 in MS subjects is 60 mg, comparable to effective RTL doses in EAE. RTL1000 is a novel approach for MS treatment that may induce immunoregulation without immunosuppression and promote neural repair.

  16. Geometrical Aspects During Formation of Compact Aggregates of Red Blood Cells

    Directory of Open Access Journals (Sweden)

    Cardoso A.V.

    2002-01-01

    Full Text Available In the past forty years considerable progress has been achieved on the knowledge of human blood as a non-Newtonian shear-thinning suspension, whose initial state, that is at rest (stasis or at very low shear rates, has a gel-like internal structure which is destroyed as shear stress increases. The main goal of this communication is to describe the role of geometrical aspects during RBC (red blood cell aggregate formation, growth and compaction on naturally aggregate (porcine blood and non-aggregate (bovine blood samples. We consider how these aspects coupled with tension equilibrium are decisive to transform red cell linear roleaux to three-dimensional aggregates or clusters. Geometrical aspects are also crucial on the compaction of red blood cell aggregates. These densely packed aggregates could precipitate out of blood- either as dangerous deposits on arterial walls, or as clots which travel in suspension until they block some crucial capillary.

  17. Dye-sensitized solar cell employing zinc oxide aggregates grown in the presence of lithium

    Science.gov (United States)

    Zhang, Qifeng; Cao, Guozhong

    2013-10-15

    Provided are a novel ZnO dye-sensitized solar cell and method of fabricating the same. In one embodiment, deliberately added lithium ions are used to mediate the growth of ZnO aggregates. The use of lithium provides ZnO aggregates that have advantageous microstructure, morphology, crystallinity, and operational characteristics. Employing lithium during aggregate synthesis results in a polydisperse collection of ZnO aggregates favorable for porosity and light scattering. The resulting nanocrystallites forming the aggregates have improved crystallinity and more favorable facets for dye molecule absorption. The lithium synthesis improves the surface stability of ZnO in acidic dyes. The procedures developed and disclosed herein also help ensure the formation of an aggregate film that has a high homogeneity of thickness, a high packing density, a high specific surface area, and good electrical contact between the film and the fluorine-doped tin oxide electrode and among the aggregate particles.

  18. Techniques for Monitoring Protein Misfolding and Aggregation in Vitro and in Living Cells

    OpenAIRE

    Gregoire, Simpson; Irwin, Jacob; Kwon, Inchan

    2012-01-01

    Protein misfolding and aggregation have been considered important in understanding many neurodegenerative diseases and recombinant biopharmaceutical production. Therefore, various traditional and modern techniques have been utilized to monitor protein aggregation in vitro and in living cells. Fibril formation, morphology and secondary structure content of amyloidogenic proteins in vitro have been monitored by molecular probes, TEM/AFM, and CD/FTIR analyses, respectively. Protein aggregation i...

  19. Velocity Variation Assessment of Red Blood Cell Aggregation with Spectral Domain Doppler Optical Coherence Tomography

    OpenAIRE

    Xu, Xiangqun; Yu, Lingfeng; Chen, Zhongping

    2010-01-01

    We propose spectral domain Doppler optical coherence tomography (SD-D-OCT) to qualitatively measure red blood cell aggregation. Variance/standard deviation (SD) of the Doppler frequency spectrum in Doppler variance imaging of flowing blood under shearing conditions was developed as a new aggregation index. In in vitro microchannel-flow experiments, porcine blood at various hematocrits with aggregation characteristics induced by dextran 500 or at the presence of plasma fibrinogen was measured ...

  20. Photometric measurements of red blood cell aggregation: light transmission versus light reflectance

    OpenAIRE

    Baskurt, O.K.; Uyuklu, M.; Hardeman, M.R.; Meiselman, H.J.

    2009-01-01

    Red blood cell (RBC) aggregation is the reversible and regular clumping in the presence of certain macromolecules. This is a clinically important phenomenon, being significantly enhanced in the presence of acute phase reactants (e. g., fibrinogen). Both light reflection (LR) and light transmission (LT) from or through thin layers of RBC suspensions during the process of aggregation are accepted to reflect the time course of aggregation. It has been recognized that the time courses of LR and L...

  1. On the use of photoacoustics to detect red blood cell aggregation

    OpenAIRE

    Hysi, Eno; Saha, Ratan K.; Kolios, Michael C.

    2012-01-01

    The feasibility of detecting red blood cell (RBC) aggregation with photoacoustics (PAs) was investigated theoretically and experimentally using human and porcine RBCs. The theoretical PA signals and spectra generated from such samples were examined for several hematocrit levels and aggregates sizes. The effect of a finite transducer bandwidth on the received PA signal was also examined. The simulation results suggest that the dominant frequency of the PA signals from non-aggregated RBCs decre...

  2. Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors

    International Nuclear Information System (INIS)

    Circulating tumor cells (CTCs) have been implicated as a population of cells that may seed metastasis and venous thromboembolism (VTE), two major causes of mortality in cancer patients. Thus far, existing CTC detection technologies have been unable to reproducibly detect CTC aggregates in order to address what contribution CTC aggregates may make to metastasis or VTE. We report here an enrichment-free immunofluorescence detection method that can reproducibly detect and enumerate homotypic CTC aggregates in patient samples. We identified CTC aggregates in 43% of 86 patient samples. The fraction of CTC aggregation was investigated in blood draws from 24 breast, 14 non-small cell lung, 18 pancreatic, 15 prostate stage IV cancer patients and 15 normal blood donors. Both single CTCs and CTC aggregates were measured to determine whether differences exist in the physical characteristics of these two populations. Cells contained in CTC aggregates had less area and length, on average, than single CTCs. Nuclear to cytoplasmic ratios between single CTCs and CTC aggregates were similar. This detection method may assist future studies in determining which population of cells is more physically likely to contribute to metastasis and VTE

  3. Prevention and dispersion of contrast media induced red cell aggregates; An in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Raininko, R.; Ylinen, S.L. (Turku Univ. (Finland). Dept. of Diagnostic Radiology)

    1990-05-01

    Red cell aggregation was observed microscopically when human blood and contrast media were mixed on glass slides. Aggregation was more frequent in low-osmolal media: mainly rouleaux were formed in ioxaglate but irregular aggregates in non-ionic media. Aggregation was similar at concentrations of 150 and 300 mg I/ml. Pre-treatment of glass slides with heparinized saline reduced red cell aggregation but saline was almost as effective. Most of the irregular aggregates dispersed when saline or heparinized saline was applied to them. Saline and heparinized saline had an identical dispersing effect. After incubation of the aggregates in iopamidol in plastic tubes for one or five minutes, saline was injected into the tubes, and after mixing the solution was poured onto glass slides and examined under the microscope. Only a few small irregular aggregates were detected in 6/60 specimens. It is concluded that ionicity of a flushing medium and shear of the injection are able to disperse red cell aggregates during angiography. (orig.).

  4. Estimation of red blood cell aggregate velocity during sedimentation using the Hough transform

    Science.gov (United States)

    Kempczyński, A.; Grzegorzewski, B.

    2008-11-01

    A method for velocity estimation of sedimenting three-dimensional (3D) red blood cell (RBC) aggregates by means of an image processing technique is proposed. Successive images of RBC suspension near the wall of a container reveal rouleaux formation, sedimentation of 3D RBC aggregates and formation of the deposit of the cells. Plots of the position versus time for the 3D RBC aggregates were extracted by a processing of successive images of the suspension. The plots exhibit a quasi-linear structures in noisy background. With the use of the Hough transform the detection of the slope of the structures was performed and the velocity of the aggregates was estimated. To show the potential of the method spatio-temporal dependence of the aggregate velocity is presented for RBCs in plasma, RBCs in Dextran and for hardened cells at haematocrit 5%.

  5. Radioimmunotherapy with Y-90-epratuzumab in patients with previously treated B-cell lymphoma. A fractionated dose-escalation study

    International Nuclear Information System (INIS)

    Aim: Fractionated RIT may improve outcome by decreasing heterogeneity in absorbed dose and by increasing therapeutic window. The humanised anti-CD22 antibody, Epratuzumab, (Immunomedics, Inc., Morris Plains, NJ) can be given repeatedly with minimal risk of neutralising Ab (HAHA), making fractionated treatment with 90Y-labelled epratuzumab possible. Materials and Methods: Patients with previously treated B-cell lymphoma received increasing number (2-4) of weekly infusions of 90Y-epratuzumab. Patients received either 185 MBq/m2 per infusion (group A), or, if they had a history of high-dose chemotherapy with stem-cell rescue, 92.5 MBq/m2 per infusion (group B). The first infusion included 150 MBq of 111Indium for scintigraphic verification of tumour targeting and dosimetry. 1.5 mg/kg epratuzumab was administered with each infusion. The treatment could be repeated once after 3 m. Results: Of 23 patients, 16 in group A and 6 in group B were evaluable for response. The RR in group A was 62% objective response (OR) and 25% CR/CRu. One patient in group B showed OR. OR was seen in aggressive and indolent lymphoma. Response was also long-lasting and event-free survival of patients showing CR/CRu was 14 to 25+ months. In group A all seven patient, receiving three infusions, showed less than grade 3 platelet and neutrophil toxicity, except for two patients suffering grade 3 neutropenia. Of five patients with 4 weekly infusions there were two patients with dose-limiting haematological toxicity (DLT), both recently treated with high dose cytosar before RIT. With criteria used the maximal tolerated dose was three infusions 185 MBq/m2. In group B no patient suffered DLT and one patient exhibited OR. Seven patients were retreated after 3 months with minor toxicity, but improvement in OR in two cases. No patient has developed HAHA. CD22 expression on tumour cells, as assessed by flow cytometry, is available in 18 of 22 patients. In group A, seven of eight patients with unequivocal

  6. The role of oxidized albumin in blood cell aggregation disturbance in burn disease

    OpenAIRE

    Levin, Grigory Ya; Egorihina, Marpha N

    2013-01-01

    The burn disease is found to be accompanied by increasing of the level of oxidized proteins of blood serum. We studied the influence of albumin oxidation rate on aggregation of platelets and erythrocytes, disaggregation of erythrocytes. The changes of blood cells aggregation associated with oxidation rate of albumin were found. Possible mechanisms of these effects are discussed.

  7. Optical tweezers study of red blood cell aggregation and disaggregation in plasma and protein solutions

    Science.gov (United States)

    Lee, Kisung; Kinnunen, Matti; Khokhlova, Maria D.; Lyubin, Evgeny V.; Priezzhev, Alexander V.; Meglinski, Igor; Fedyanin, Andrey A.

    2016-03-01

    Kinetics of optical tweezers (OT)-induced spontaneous aggregation and disaggregation of red blood cells (RBCs) were studied at the level of cell doublets to assess RBC interaction mechanics. Measurements were performed under in vitro conditions in plasma and fibrinogen and fibrinogen + albumin solutions. The RBC spontaneous aggregation kinetics was found to exhibit different behavior depending on the cell environment. In contrast, the RBC disaggregation kinetics was similar in all solutions qualitatively and quantitatively, demonstrating a significant contribution of the studied proteins to the process. The impact of the study on assessing RBC interaction mechanics and the protein contribution to the reversible RBC aggregation process is discussed.

  8. Nuclear deterrence: Inherent escalation?

    International Nuclear Information System (INIS)

    Despite 40 years of peace between the super powers, there is increasing clamor to the effect that nuclear war between the super powers is imminent; or could occur through escalation from a minor conflict; or could result from harsh rhetoric (but only on the part of the U.S.) in the super power dialogue. The factor that is ignored is that a massive nuclear attack would be rational ONLY if that attack could inflict such damage that the other super power could not launch a significant retaliatory nuclear attack. ONLY in this circumstance would there be any profit in launching an initial Strategic Nuclear Attack. This First Strike capability is not now possessed nor projected to be developed by either super power. As long as ANY possible Strategic Nuclear Attack against the national territory of one super power would be insufficient to prevent an equally destructive retaliatory attack, then a Strategic Nuclear Attack would inevitably result in the destruction of both and would be profitless, hence, pointless. This situation describes Mutually Assured Destruction (MAD), the governing conflict paradigm applicable to both super powers. The only convential attack that would even remotely rival the national-destruction potential of a Strategic Nuclear Attack and could cause the attacked power to consider launching a retaliatory Strategic Nuclear Attack would be a massive land-air invasion/occupation of one super power by the other. Since neither super power can successfully execute such a conventional invasion/occupation, this situation is moot. The geo-political environments of the two super powers are so asymmetrical and their military positions so symmetrical that the probability of ANY forseeable situation resulting in their resorting to a Strategic Nuclear Exchange is vanishingly small. It is possible escape the Chicken-Little syndrome and, instead, devote energy to ensuring the maintenance of this favorable, but fragile, world system

  9. Detection and characterization of red blood cell (RBC) aggregation with photoacoustics

    Science.gov (United States)

    Hysi, Eno; Saha, Ratan K.; Rui, Min; Kolios, Michael C.

    2012-02-01

    Red blood cells (RBCs) aggregate in the presence of increased plasma fibrinogen and low shear forces during blood flow. RBC aggregation has been observed in deep vein thrombosis, sepsis and diabetes. We propose using photoacoustics (PA) as a non-invasive imaging modality to detect RBC aggregation. The theoretical and experimental feasibility of PA for detecting and characterizing aggregation was assessed. A simulation study was performed to generate PA signals from non-aggregated and aggregated RBCs using a frequency domain approach and to study the PA signals' dependence on hematocrit and aggregate size. The effect of the finite bandwidth nature of transducers on the PA power spectra was also investigated. Experimental confirmation of theoretical results was conducted using porcine RBC samples exposed to 1064 nm optical wavelength using the Imagio Small Animal PA imaging system (Seno Medical Instruments, Inc., San Antonio, TX). Aggregation was induced with Dextran-70 (Sigma-Aldrich, St. Louis, MO) and the effect of hematocrit and aggregation level was investigated. The theoretical and experimental PA signal amplitude increased linearly with increasing hematocrit. The theoretical dominant frequency content of PA signals shifted towards lower frequencies (<30 MHz) and 9 dB enhancements in spectral power were observed as the size of aggregates increased compared to non-aggregating RBCs. Calibration of the PA spectra with the transducer response obtained from a 200 nm gold film was performed to remove system dependencies. Analysis of the spectral parameters from the calibrated spectra suggested that PA can assess the degree of aggregation at multiple hematocrit and aggregation levels.

  10. Polyvinylpyrrolidone- (PVP-) coated silver aggregates for high performance surface-enhanced Raman scattering in living cells

    International Nuclear Information System (INIS)

    A biocompatible and stable surface-enhanced Raman scattering (SERS) probe has been successfully synthesized through a simple route with silver aggregates. Polyvinylpyrrolidone (PVP), a biocompatible polymer, was utilized to control the aggregation process and improve the chemical stability of the aggregates. Extinction spectroscopy and TEM results show the aggregation degree and core-shell structure of the probe. It is found that when we employ 4-mercaptobenzoic acid (4MBA), crystal violet (CV), Rhodamine 6G (R6G) or 4,4'-bipyridine molecules as Raman reporters, the SERS signal from the proposed probe can remain at a high level under aggressive chemical environments, even after being incorporated into living cells. In comparison with the traditional probes without the PVP shell, the new ones exhibit strong surface-enhanced effects and low toxicity towards living cells. We demonstrate that the PVP-coated silver aggregates are highly SERS effective, for which the fabrication protocol is advantageous in its simplicity and reproducibility.

  11. Red blood cell aggregation, aggregate strength and oxygen transport potential of blood are abnormal in both homozygous sickle cell anemia and sickle-hemoglobin C disease

    OpenAIRE

    Tripette, Julien; Alexy, Tamas; Hardy-Dessources, Marie-Dominique; Mougenel, Daniele; Beltan, Eric; Chalabi, Tawfik; Chout, Roger; Etienne-Julan, Maryse; Hue, Olivier; Meiselman, Herbert J.; Connes, Philippe

    2009-01-01

    Recent evidence suggests that red cell aggregation and the ratio of hematocrit to blood viscosity, an index of the oxygen transport potential of blood, might considerably modulate blood flow dynamics in the microcirculation. The findings of this study indicate that patients with sickle cell disease and those with sickle cell hemoglobin C disease have low ratios of hematocrit to blood viscosity as compared to normal controls. This may play a role in tissue hypoxia and clinical status of these ...

  12. Combined modeling of cell aggregation and adhesion mediated by receptor–ligand interactions under shear flow

    Directory of Open Access Journals (Sweden)

    Yu Du

    2015-11-01

    Full Text Available Blood cell aggregation and adhesion to endothelial cells under shear flow are crucial to many biological processes such as thrombi formation, inflammatory cascade, and tumor metastasis, in which these cellular interactions are mainly mediated by the underlying receptor–ligand bindings. While theoretical modeling of aggregation dynamics and adhesion kinetics of interacting cells have been well studied separately, how to couple these two processes remains unclear. Here we develop a combined model that couples cellular aggregation dynamics and adhesion kinetics under shear flow. The impacts of shear rate (or shear stress and molecular binding affinity were elucidated. This study provides a unified model where the action of a fluid flow drives cell aggregation and adhesion under the modulations of the mechanical shear flow and receptor–ligand interaction kinetics. It offers an insight into understanding the relevant biological processes and functions.

  13. Bone marrow mesenchymal stem cell aggregate: an optimal cell therapy for full-layer cutaneous wound vascularization and regeneration

    Science.gov (United States)

    An, Yulin; wei, Wei; Jing, Huan; Ming, Leiguo; Liu, Shiyu; Jin, Yan

    2015-01-01

    Cutaneous wounds are among the most common soft tissue injuries. Wounds involving dermis suffer more from outside influence and higher risk of chronic inflammation. Therefore the appearance and function restoration has become an imperative in tissue engineering research. In this study, cell-aggregates constructed with green fluorescent protein-expressing (GFP+) rat bone marrow mesenchymal stem cells (BMMSCs) were applied to rat acute full-layer cutaneous wound model to confirm its pro-regeneration ability and compare its regenerative efficacy with the currently thriving subcutaneous and intravenous stem cell administration strategy, with a view to sensing the advantages, disadvantages and the mechanism behind. According to results, cell-aggregates cultured in vitro enjoyed higher expression of several pro-healing genes than adherent cultured cells. Animal experiments showed better vascularization along with more regular dermal collagen deposition for cell-aggregate transplanted models. Immunofluorescence staining on inflammatory cells indicated a shorter inflammatory phase for cell-aggregate group, which was backed up by further RT-PCR. The in situ immunofluorescence staining manifested a higher GFP+-cell engraftment for cell-aggregate transplanted models versus cell administered ones. Thus it is safe to say the BMMSCs aggregate could bring superior cutaneous regeneration for full layer cutaneous wound to BMMSCs administration, both intravenous and subcutaneous. PMID:26594024

  14. Physical and chemical effects of red cells in the shear-induced aggregation of human platelets.

    OpenAIRE

    Goldsmith, H L; Bell, D N; Braovac, S; Steinberg, A.; McIntosh, F

    1995-01-01

    Both chemical and physical effects of red cells have been implicated in the spontaneous aggregation of platelets in sheared whole blood (WB). To determine whether the chemical effect is due to ADP leaking from the red cells, a previously described technique for measuring the concentration and size of single platelets and aggregates was used to study the shear-induced aggregation of platelets in WB flowing through 1.19-mm-diameter polyethylene tubing in the presence and absence of the ADP scav...

  15. 14-3-3ζ Mediates Tau Aggregation in Human Neuroblastoma M17 Cells.

    Science.gov (United States)

    Li, Tong; Paudel, Hemant K

    2016-01-01

    Microtubule-associated protein tau is the major component of paired helical filaments (PHFs) associated with the neuropathology of Alzheimer's disease (AD). Tau in the normal brain binds and stabilizes microtubules. Tau isolated from PHFs is hyperphosphorylated, which prevents it from binding to microtubules. Tau phosphorylation has been suggested to be involved in the development of NFT pathology in the AD brain. Recently, we showed that 14-3-3ζ is bound to tau in the PHFs and when incubated in vitro with 14-3-3ζ, tau formed amorphous aggregates, single-stranded straight filaments, double stranded ribbon-like filaments and PHF-like filaments that displayed close resemblance with corresponding ultrastructures of AD brain. Surprisingly however, phosphorylated and non-phosphorylated tau aggregated in a similar manner, indicating that tau phosphorylation does not affect in vitro tau aggregation (Qureshi et al (2013) Biochemistry 52, 6445-6455). In this study, we have examined the role of tau phosphorylation in tau aggregation in cellular level. We have found that in human M17 neuroblastoma cells, tau phosphorylation by GSK3β or PKA does not cause tau aggregation, but promotes 14-3-3ζ-induced tau aggregation by destabilizing microtubules. Microtubule disrupting drugs also promoted 14-3-3ζ-induced tau aggregation without changing tau phosphorylation in M17 cell. In vitro, when incubated with 14-3-3ζ and microtubules, nonphosphorylated tau bound to microtubules and did not aggregate. Phosphorylated tau on the other hand did not bind to microtubules and aggregated. Our data indicate that microtubule-bound tau is resistant to 14-3-3ζ-induced tau aggregation and suggest that tau phosphorylation promotes tau aggregation in the brain by detaching tau from microtubules and thus making it accessible to 14-3-3ζ. PMID:27548710

  16. Rapid Formation of Cell Aggregates and Spheroids Induced by a "Smart" Boronic Acid Copolymer.

    Science.gov (United States)

    Amaral, Adérito J R; Pasparakis, George

    2016-09-01

    Cell surface engineering has emerged as a powerful approach to forming cell aggregates/spheroids and cell-biomaterial ensembles with significant uses in tissue engineering and cell therapeutics. Herein, we demonstrate that cell membrane remodeling with a thermoresponsive boronic acid copolymer induces the rapid formation of spheroids using either cancer or cardiac cell lines under conventional cell culture conditions at minute concentrations. It is shown that the formation of well-defined spheroids is accelerated by at least 24 h compared to non-polymer-treated controls, and, more importantly, the polymer allows for fine control of the aggregation kinetics owing to its stimulus response to temperature and glucose content. On the basis of its simplicity and effectiveness to promote cellular aggregation, this platform holds promise in three-dimensional tissue/tumor modeling and tissue engineering applications. PMID:27571512

  17. Large-scale RNA interference screening in mammalian cells identifies novel regulators of mutant huntingtin aggregation.

    Directory of Open Access Journals (Sweden)

    Tomoyuki Yamanaka

    Full Text Available In polyglutamine (polyQ diseases including Huntington's disease (HD, mutant proteins containing expanded polyQ stretch form aggregates in neurons. Genetic or RNAi screenings in yeast, C. elegans or Drosophila have identified multiple genes modifying polyQ aggregation, a few of which are confirmed effective in mammals. However, the overall molecular mechanism underlying polyQ protein aggregation in mammalian cells still remains obscure. We here perform RNAi screening in mouse neuro2a cells to identify mammalian modifiers for aggregation of mutant huntingtin, a causative protein of HD. By systematic cell transfection and automated cell image analysis, we screen ∼ 12000 shRNA clones and identify 111 shRNAs that either suppress or enhance mutant huntingtin aggregation, without altering its gene expression. Classification of the shRNA-targets suggests that genes with various cellular functions such as gene transcription and protein phosphorylation are involved in modifying the aggregation. Subsequent analysis suggests that, in addition to the aggregation-modifiers sensitive to proteasome inhibition, some of them, such as a transcription factor Tcf20, and kinases Csnk1d and Pik3c2a, are insensitive to it. As for Tcf20, which contains polyQ stretches at N-terminus, its binding to mutant huntingtin aggregates is observed in neuro2a cells and in HD model mouse neurons. Notably, except Pik3c2a, the rest of the modifiers identified here are novel. Thus, our first large-scale RNAi screening in mammalian system identifies previously undescribed genetic players that regulate mutant huntingtin aggregation by several, possibly mammalian-specific mechanisms.

  18. CEACAM1 mediates B cell aggregation in central nervous system autoimmunity.

    Science.gov (United States)

    Rovituso, Damiano M; Scheffler, Laura; Wunsch, Marie; Kleinschnitz, Christoph; Dörck, Sebastian; Ulzheimer, Jochen; Bayas, Antonios; Steinman, Lawrence; Ergün, Süleyman; Kuerten, Stefanie

    2016-01-01

    B cell aggregates in the central nervous system (CNS) have been associated with rapid disease progression in patients with multiple sclerosis (MS). Here we demonstrate a key role of carcinoembryogenic antigen-related cell adhesion molecule1 (CEACAM1) in B cell aggregate formation in MS patients and a B cell-dependent mouse model of MS. CEACAM1 expression was increased on peripheral blood B cells and CEACAM1(+) B cells were present in brain infiltrates of MS patients. Administration of the anti-CEACAM1 antibody T84.1 was efficient in blocking aggregation of B cells derived from MS patients. Along these lines, application of the monoclonal anti-CEACAM1 antibody mCC1 was able to inhibit CNS B cell aggregate formation and significantly attenuated established MS-like disease in mice in the absence of any adverse effects. CEACAM1 was co-expressed with the regulator molecule T cell immunoglobulin and mucin domain -3 (TIM-3) on B cells, a novel molecule that has recently been described to induce anergy in T cells. Interestingly, elevated coexpression on B cells coincided with an autoreactive T helper cell phenotype in MS patients. Overall, these data identify CEACAM1 as a clinically highly interesting target in MS pathogenesis and open new therapeutic avenues for the treatment of the disease. PMID:27435215

  19. Cost escalation in nuclear power

    International Nuclear Information System (INIS)

    This report is concerned with the escalation of capital costs of nuclear central station power plants between the early 1960s and the present. The report presents an historical overview of the development of the nuclear power industry and cost escalation in the industry, using existing data on orders and capital costs. New data are presented on regulatory delays in the licensing process, derived from a concurrent study being carried on in the Social Science group at Caltech. The conclusions of the study are that nuclear capital costs have escalated more rapidly than the GNP deflator or the construction industry price index. Prior to 1970, cost increases are related to bottleneck problems in the nuclear construction and supplying industries and the regulatory process; intervenors play only a minor role in cost escalation. After 1970, generic changes introduced into the licensing process by intervenors (including environmental impact reviews, antitrust reviews, more stringent safety standards) dominate the cost escalation picture, with bottlenecks of secondary importance. Recent increases in the time from application for a construction permit to commercial operation are related not only to intervenor actions, but also to suspensions, cancellations or postponements of construction by utilities due to unfavorable demand or financing conditions

  20. Changes of RBC aggregation in oxygenation-deoxygenation: pH dependency and cell morphology.

    Science.gov (United States)

    Cicha, Iwona; Suzuki, Yoji; Tateishi, Norihiko; Maeda, Nobuji

    2003-06-01

    The effects of the oxygenation-deoxygenation process on red blood cell (RBC) aggregation were examined in relation to morphological changes in RBCs and the contribution of CO(2). A low-shear rheoscope was used to measure the rate of rouleaux (one-dimensional aggregate) formation in diluted autologous plasma exposed to gas mixtures with different Po(2) and Pco(2). RBC indexes and RBC suspension pH were measured for the oxygenated or the deoxygenated condition, and the cell shape was observed with a scanning electron microscope. In the oxygenation-deoxygenation process, the rate of rouleaux formation increased with rising pH of the RBC suspension, which was lowered in the presence of CO(2). The rate increased with increasing mean corpuscular hemoglobin concentration (thus the cells shrank), which increased with rising pH and decreased in the presence of CO(2). With rising pH, cell diameter increased and cell thickness decreased (thus the cell flattened). In addition, slight echinocytosis was induced in the presence of CO(2), and the aggregation was reduced by the morphological change. In conclusion, RBC aggregation in the oxygenation-deoxygenation process is mainly influenced by the pH-dependent change in the surface area-to-volume ratio of the cells, and the aggregation is modified by CO(2)-induced acidification and the accompanying changes in mean corpuscular hemoglobin concentration and cell shape. PMID:12742832

  1. Synergy between phorbol esters, 1-oleyl-2-acetylglycerol, urushiol, and calcium ionophore in eliciting aggregation of marine sponge cells.

    OpenAIRE

    Weissmann, G; Azaroff, L; Davidson, S.; Dunham, P

    1986-01-01

    Aggregation of marine sponge cells (Microciona prolifera) resembles stimulus-response coupling of higher organisms in which activation of protein kinase C and movements of intracellular Ca provide twin signals. We now report that activators of protein kinase C (phorbol esters) and ionomycin act synergistically to aggregate sponge cells. Surprisingly--since extracellular Ca is required for integrity of the species-specific aggregation factor--synergistic aggregation proceeded in the complete a...

  2. Using Generalized Equivalent Uniform Dose Atlases to Combine and Analyze Prospective Dosimetric and Radiation Pneumonitis Data From 2 Non-Small Cell Lung Cancer Dose Escalation Protocols

    Energy Technology Data Exchange (ETDEWEB)

    Liu Fan; Yorke, Ellen D. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Belderbos, Jose S.A.; Borst, Gerben R. [The Netherlands Cancer Institute, Antoni Van Leeuwenhoek Hospital, Amsterdam (Netherlands); Rosenzweig, Kenneth E. [Mount Sinai School of Medicine, New York, New York (United States); Lebesque, Joos V. [The Netherlands Cancer Institute, Antoni Van Leeuwenhoek Hospital, Amsterdam (Netherlands); Jackson, Andrew, E-mail: jacksona@mskcc.org [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-01-01

    Purpose: To demonstrate the use of generalized equivalent uniform dose (gEUD) atlas for data pooling in radiation pneumonitis (RP) modeling, to determine the dependence of RP on gEUD, to study the consistency between data sets, and to verify the increased statistical power of the combination. Methods and Materials: Patients enrolled in prospective phase I/II dose escalation studies of radiation therapy of non-small cell lung cancer at Memorial Sloan-Kettering Cancer Center (MSKCC) (78 pts) and the Netherlands Cancer Institute (NKI) (86 pts) were included; 10 (13%) and 14 (17%) experienced RP requiring steroids (RPS) within 6 months after treatment. gEUD was calculated from dose-volume histograms. Atlases for each data set were created using 1-Gy steps from exact gEUDs and RPS data. The Lyman-Kutcher-Burman model was fit to the atlas and exact gEUD data. Heterogeneity and inconsistency statistics for the fitted parameters were computed. gEUD maps of the probability of RPS rate {>=}20% were plotted. Results: The 2 data sets were homogeneous and consistent. The best fit values of the volume effect parameter a were small, with upper 95% confidence limit around 1.0 in the joint data. The likelihood profiles around the best fit a values were flat in all cases, making determination of the best fit a weak. All confidence intervals (CIs) were narrower in the joint than in the individual data sets. The minimum P value for correlations of gEUD with RPS in the joint data was .002, compared with P=.01 and .05 for MSKCC and NKI data sets, respectively. gEUD maps showed that at small a, RPS risk increases with gEUD. Conclusions: The atlas can be used to combine gEUD and RPS information from different institutions and model gEUD dependence of RPS. RPS has a large volume effect with the mean dose model barely included in the 95% CI. Data pooling increased statistical power.

  3. Aggregate formation and suspension culture of human pluripotent stem cells and differentiated progeny.

    Science.gov (United States)

    Hookway, Tracy A; Butts, Jessica C; Lee, Emily; Tang, Hengli; McDevitt, Todd C

    2016-05-15

    Culture of human pluripotent stem cells (hPSC) as in vitro multicellular aggregates has been increasingly used as a method to model early embryonic development. Three-dimensional assemblies of hPSCs facilitate interactions between cells and their microenvironment to promote morphogenesis, analogous to the multicellular organization that accompanies embryogenesis. In this paper, we describe a method for reproducibly generating and maintaining populations of homogeneous three-dimensional hPSC aggregates using forced aggregation and rotary orbital suspension culture. We propose solutions to several challenges associated with the consistent formation and extended culture of cell spheroids generated from hPSCs and their differentiated progeny. Further, we provide examples to demonstrate how aggregation can be used as a tool to select specific subpopulations of cells to create homotypic spheroids, or as a means to introduce multiple cell types to create heterotypic tissue constructs. Finally, we demonstrate that the aggregation and rotary suspension method can be used to support culture and maintenance of hPSC-derived cell populations representing each of the three germ layers, underscoring the utility of this platform for culturing many different cell types. PMID:26658353

  4. Escalation: How Much is Enough?

    Science.gov (United States)

    Butts, Glenn

    2007-01-01

    Determining the escalation percentage to an estimate is often the subject of fierce debate. Cost increases are determined by dynamic relati onships between many factors, including acts of nature, interest rate s, oil prices, global commodity markets, wars, wage rates, and the ov erall health of the economy, as well as supply and demand for the required goods or services. How much escalation is enough? Are the recen t price increases temporary aberrations, or will they continue to pla gue us? This paper examines historical escalation rates, as well as i ndications of trends. Various analysis methods -- Monte Carlo simulations, neural networks, trend impact analysis, and the Delphi method -- are examined in an attempt to determine future trends.

  5. Simplified variant of an optical chip to evaluate aggregation of red blood cells

    Science.gov (United States)

    Toderi, Martín. A.; Riquelme, Bibiana D.; Castellini, Horacio V.

    2015-06-01

    Traditional techniques to evaluate the aggregation of red blood cells by optical methods require large sample volume and provide parameters that vary significantly from one method to another. A simplified variant of a chip system previously developed by Shin et al. (2009)1 based on light transmission for measuring erythrocyte aggregation is presented. Through a detailed analysis of intensity versus time curves, relevant information about erythrocyte aggregation and its variables is obtained. Parameters that provide more accuracy for the diagnosis of patients in order to have an immediate application in Clinical Medicine are proposed.

  6. Sponge cell reaggregation: Cellular structure and morphogenetic potencies of multicellular aggregates.

    Science.gov (United States)

    Lavrov, Andrey I; Kosevich, Igor A

    2016-02-01

    Sponges (phylum Porifera) are one of the most ancient extant multicellular animals and can provide valuable insights into origin and early evolution of Metazoa. High plasticity of cell differentiations and anatomical structure is characteristic feature of sponges. Present study deals with sponge cell reaggregation after dissociation as the most outstanding case of sponge plasticity. Dynamic of cell reaggregation and structure of multicellular aggregates of three demosponge species (Halichondria panicea (Pallas, 1766), Haliclona aquaeductus (Sсhmidt, 1862), and Halisarca dujardinii Johnston, 1842) were studied. Sponge tissue dissociation was performed mechanically. Resulting cell suspensions were cultured at 8-10°C for at least 5 days. Structure of multicellular aggregates was studied by light, transmission and scanning electron microscopy. Studied species share common stages of cell reaggregation-primary multicellular aggregates, early-stage primmorphs and primmorphs, but the rate of reaggregation varies considerably among species. Only cells of H. dujardinii are able to reconstruct functional and viable sponge after primmorphs formation. Sponge reconstruction in this species occurs due to active cell locomotion. Development of H. aquaeductus and H. panicea cells ceases at the stages of early primmorphs and primmorphs, respectively. Development of aggregates of these species is most likely arrested due to immobility of the majority of cells inside them. However, the inability of certain sponge species to reconstruct functional and viable individuals during cell reaggregation may be not a permanent species-specific characteristic, but depends on various factors, including the stage of the life cycle and experimental conditions. PMID:26863993

  7. Composition of EPS fractions from suspended sludge and biofilm and their roles in microbial cell aggregation.

    Science.gov (United States)

    Zhang, Peng; Fang, Fang; Chen, You-Peng; Shen, Yu; Zhang, Wei; Yang, Ji-Xiang; Li, Chun; Guo, Jin-Song; Liu, Shao-Yang; Huang, Yang; Li, Shan; Gao, Xu; Yan, Peng

    2014-12-01

    The adhesion and aggregation properties of microbial cell are closely related to extracellular polymeric substances (EPS). In this work, the composition and physicochemical characteristics of EPS in biofilm and suspended sludge (S-sludge) were determined to evaluate their roles in microbial cell aggregation. Raman spectroscopy and three-dimensional fluorescence spectra have been employed to reveal each EPS fraction in different composition. The flocculating capacity of each EPS fraction in the S-sludge shows extraordinary activity, comparing its counterpart in biofilm. Microbial cell surfaces present high hydrophobicity and increased zeta potentials upon EPS extraction. In addition, the respective contribution of EPS to cell aggregating was elucidated. The contribution of combined SEPS and LB-EPS was 23% for S-sludge sample, whereas that was negligible for biofilm sample. The contribution of LB-EPS and TB-EPS were 16% and 30% for S-sludge sample, and -6% and negligible for biofilm sample, respectively. Therefore, EPS promoted the S-sludge cells to aggregate, while in contrast, they showed a negligible or negative effect on the biofilm cells aggregating. PMID:24968163

  8. Quantification of the aggregation of magnetic nanoparticles with different polymeric coatings in cell culture medium

    OpenAIRE

    Eberbeck, D; Kettering, M; Bergemann, C; Zirpel, P; Hilger, I; Trahms, L.

    2010-01-01

    Abstract The knowledge of the physico-chemical characteristics of magnetic nanoparticles (MNPs) is essential to enhance the efficacy of MNP-based therapeutic treatments (e.g. magnetic heating, magnetic drug targeting). According to the literature, the MNP uptake by cells may depend on the coating of MNPs, the surrounding medium as well as on the aggregation behaviour of the MNPs. Therefore, in this study, the aggregation behaviour of MNPs in various media was investigated. MNPs with differ...

  9. The Hydrodynamic Radii of Macromolecules and Their Effect on Red Blood Cell Aggregation

    OpenAIRE

    Armstrong, J. K.; Wenby, R. B.; Meiselman, H.J.; Fisher, T.C.

    2004-01-01

    The effects of nonionic polymers on human red blood cell (RBC) aggregation were investigated. The hydrodynamic radius (Rh) of individual samples of dextran, polyvinylpyrrolidone, and polyoxyethylene over a range of molecular weights (1500–2,000,000) were calculated from their intrinsic viscosities using the Einstein viscosity relation and directly measured by quasi-elastic light scattering, and the effect of each polymer sample on RBC aggregation was studied by nephelometry and low-shear visc...

  10. Freely suspended cellular "backpacks" lead to cell aggregate self-assembly.

    Science.gov (United States)

    Swiston, Albert J; Gilbert, Jonathan B; Irvine, Darrell J; Cohen, Robert E; Rubner, Michael F

    2010-07-12

    Cellular "backpacks" are a new type of anisotropic, nanoscale thickness microparticle that may be attached to the surface of living cells creating a "bio-hybrid" material. Previous work has shown that these backpacks do not impair cell viability or native functions such as migration in a B and T cell line, respectively. In the current work, we show that backpacks, when added to a cell suspension, assemble cells into aggregates of reproducible size. We investigate the efficiency of backpack-cell binding using flow cytometry and laser diffraction, examine the influence of backpack diameter on aggregate size, and show that even when cell-backpack complexes are forced through small pores, backpacks are not removed from the surfaces of cells. PMID:20527876

  11. Effect of Thai medicinal plant extracts on cell aggregation of Escherichia coli O157: H7.

    Directory of Open Access Journals (Sweden)

    Limsuwan, S.

    2005-08-01

    Full Text Available Medicinal plants have been used for treating diarrhoea but the interference mechanisms are not clearly understood. One possible hypothesis is that of an effect on cell surface hydrophobicity of microbial cells. In this study, we examined cell aggregation affected by crude extracts of Thai medicinal plants on cell surface hydrophobicity of Escherichia coli strains by salt aggregation test. Correlation between minimal inhibitory concentration and cell aggregation was performed. Aqueous and ethanolic extracts of 8 medicinal plants including Acacia catechu, Holarrhena antidysenterica, Peltophorum pterocarpum, Piper sarmentosum, Psidium guajava, Punica granatum, Quercus infectoria, and Tamarindus indica were tested with E. coli O157: H7 and other E. coli strains isolated from human, porcine, and foods. Aqueous extracts of Peltophorum pterocarpum, Psidium guajava, and Punica granatum were highly effective against E. coli O157: H7 with the MIC values of 0.09 to 0.39, 0.19 to 0.78, and 0.09 to 1.56 mg/ml, respectively. Ethanolic extract of Quercus infectoria and Punica granatum demonstrated good MIC values of 0.09 to 0.78, and 0.19 to 0.78 mg/ml, respectively. It was established that aqueous extracts of Punica granatum and Piper sarmentosum at high concentration (25 mg/ml enhanced cell aggregation of almost all E. coli strains while aqueous and ethanolic extracts ofQuercus infectoria enhanced cell aggregation of some E. coli strains. Correlation between minimal inhibitory concentration and cell aggregation was not found in this study.

  12. Effect of x-ray contrast media on spontaneous red blood cell aggregation

    International Nuclear Information System (INIS)

    Using the method of registration of dynamics of red blood cell aggregation by light scattering and light microscopy it has been observed that hight osmolality of X-ray contrast media, their lipotropy and some peculiarities of the molecular structure determined red blood cell structure-functional changes

  13. Exploring new biological functions of amyloids: bacteria cell agglutination mediated by host protein aggregation.

    Directory of Open Access Journals (Sweden)

    Marc Torrent

    Full Text Available Antimicrobial proteins and peptides (AMPs are important effectors of the innate immune system that play a vital role in the prevention of infections. Recent advances have highlighted the similarity between AMPs and amyloid proteins. Using the Eosinophil Cationic Protein as a model, we have rationalized the structure-activity relationships between amyloid aggregation and antimicrobial activity. Our results show how protein aggregation can induce bacteria agglutination and cell death. Using confocal and total internal reflection fluorescence microscopy we have tracked the formation in situ of protein amyloid-like aggregates at the bacteria surface and on membrane models. In both cases, fibrillar aggregates able to bind to amyloid diagnostic dyes were detected. Additionally, a single point mutation (Ile13 to Ala can suppress the protein amyloid behavior, abolishing the agglutinating activity and impairing the antimicrobial action. The mutant is also defective in triggering both leakage and lipid vesicle aggregation. We conclude that ECP aggregation at the bacterial surface is essential for its cytotoxicity. Hence, we propose here a new prospective biological function for amyloid-like aggregates with potential biological relevance.

  14. Submicrometer-scale ZnO Composite Aggregate Arrays Photoanodes for Dye-sensitized Solar Cells

    Institute of Scientific and Technical Information of China (English)

    Wei Jia; Suihu Dang; Hairui Liu; Zhuxia Zhang; Tianbao Li; Xuguang Liu; Bingshe Xu

    2013-01-01

    Submicrometer-scale ZnO composite aggregate arrays of nanorods and nanoparticles were prepared by simple wet-chemical route and studied as dye-sensitized solar cells (DSSCs) photoanodes.The ZnO composite aggregate arrays significantly improved the efficiency of DSSCs due to their relatively high surface area,fast electron transport,and enhanced light-scattering capability.A short current density (Jsc) of 11.7 mA/cm2 and an overall solar-to-electric energy conversion efficiency (η) of 3.17% were achieved for the ZnO composite aggregate DSSCs,which were much higher than those obtained for the monodisperse aggregate DSSCs (Jsc=6.9mA/cm2,η=1.51 %) and ZnO nanorod array DSSCs (Jsc =4.2 mA/cm2,η=0.61%).

  15. MODELS FOR MOUSE CHIMERA PRODUCTION: AGGREGATION OF ES CELLS WITH CLEAVAGE STAGE EMBRYOS

    Directory of Open Access Journals (Sweden)

    STANCA CLAUDIA

    2007-01-01

    Full Text Available In a mutant ES cells↔ wild-type embryo chimera, ES cells behave more like epiblastcells. They can contribute to the primitive ectoderm layers, which give rise to all theembryonic tissues and some extraembryonic tissues (Beddington and Robertson,1989, but not to trophectoderm or primitive endoderm. Using transgenic ES celllines, aggregated with cleavage stage host embryo, ES cells can integrate randomlyin the embryo proper. If they will be take part in the formation of ICM (inner cellmass, it will be possible to obtain germline chimera animals. To generate ES cells↔ cleavage stage host embryo chimeras, we used (CD-1 mice as donors of hostembryos as well as recipients of manipulated embryos. For chimera production, weused fluorescent-labeled ES cell line (CD1/EGFP, because in this case we canfollow the fate of ES cells during the embryonic development. We produced thechimers using “aggregation chimera technique”. 8 cells stage zona pellucida free,mouse embryos were aggregated in an aggregation plates, with a clump of ES cells(10 – 15 cells. The chimera embryos were cultivated for 24 hours in the incubator(at 37 °C, 5% CO2 in air. The chimera blastocysts resulted after cultivation, weretransferred to the uterus of the 2.5-dpc pseudo pregnant females.

  16. A Phase 1 Dose-Escalation Study of ASP2409, a Selective T-Cell Costimulation Inhibitor, in Stable Rheumatoid Arthritis Patients on Methotrexate Therapy.

    Science.gov (United States)

    Zhang, Wenhui; Kernstock, Robert M; Karrer, Erik E; Cohen, Stanley B; Chindalore, Vishala L; Kivitz, Alan J; Blahunka, Paul C; Delgado-Herrera, Leticia; Zeiher, Bernhardt G; Samberg, Nancy L; Garg, Jay P

    2016-07-01

    ASP2409 represents a new class of CTLA4-Ig molecules with higher binding avidity and selectivity to CD86. This first-in-human study was to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of ASP2409 in stable rheumatoid arthritis patients on methotrexate therapy with a randomized, double-blind, placebo-controlled dose-escalation study design. Patients were enrolled and randomized in each of 8 dose-escalation cohorts ranging from 0.001 to 3.0 mg/kg to receive either ASP2409 or placebo in a sequential manner. Escalation to higher dose levels occurred in the absence of dose-limiting toxicity. A total of 57 patients completed the study. ASP2409 showed nonlinear PK over the dose range of 0.01 to 3.0 mg/kg following a single intravenous administration, indicating target-mediated drug disposition. Area under the concentration-time curve (AUC) and maximum concentration (Cmax ) increased at a greater than dose-proportional rate. The half-life of ASP2409 increased dose dependently and ranged from 1.57 to 6.68 days. ASP2409 showed a dose-dependent increase in the extent and duration of CD86 receptor occupancy. There were no clinically relevant safety issues up to a single dose of 3.0 mg/kg. No maximum tolerated dose was reached. The incidence and duration of antidrug antibodies did not correlate with adverse events. ClinicalTrials.gov identifier: NCT02171143. PMID:27310327

  17. Is Intermediate Radiation Dose Escalation With Concurrent Chemotherapy for Stage III Non–Small-Cell Lung Cancer Beneficial? A Multi-Institutional Propensity Score Matched Analysis

    International Nuclear Information System (INIS)

    Purpose: The clinical benefits and risks of dose escalation (DE) for stage III non–small-cell lung cancer (NSCLC) remain uncertain despite the results from Radiation Therapy Oncology Group (RTOG) protocol 0617. There is significant heterogeneity of practice, with many clinicians prescribing intermediate dose levels between the 0617 study arms of 60 and 74 Gy. This study investigated whether this strategy is associated with any survival benefits/risks by analyzing a large multi-institutional database. Methods and Materials: An individual patient database of stage III NSCLC patients treated with radical intent concurrent chemoradiation therapy was created (13 institutions, n=1274 patients). Patients were divided into 2 groups based on tumor Biological Effective Dose at 10 Gy (BED 10): those receiving standard dose (SD; n=552), consisting of 72Gy ≤ BED 10 ≤ 76.8 Gy (eg 60-64 Gy/30-32 fractions [fr]), and those receiving intermediate dose (ID; n=497), consisting of 76.8Gy < BED 10 < 100.8 Gy (eg >64 Gy/32 fr and <74 Gy/37 fr), with lower-dose patients (n=225) excluded from consideration. Patients were then matched using propensity scores, leading to 2 matched groups of 196 patients. Outcomes were compared using various statistics including interquartile range (IQR), Kaplan-Meier curves, and adjusted Cox regression analysis. Results: Matched groups were found to be balanced except for N stage (more N3 disease in SD), median treatment year (SD in 2003; ID in 2007), platinum and taxane chemotherapy (SD in 28%; ID in 39%), and median follow-up (SD were 89 months; ID were 40 months). Median dose fractionation was 60 Gy/30 fr in SD (BED 10 IQR: 72.0-75.5 Gy) and 66 Gy/33 fr (BED 10 IQR: 78.6-79.2 Gy) in ID. Survival curves for SD and ID matched cohorts were statistically similar (P=.27); however, a nonstatistically significant trend toward better survival for ID was observed after 15 months (median survival SD: 19.3 months; ID: 21.0

  18. Is Intermediate Radiation Dose Escalation With Concurrent Chemotherapy for Stage III Non–Small-Cell Lung Cancer Beneficial? A Multi-Institutional Propensity Score Matched Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, George, E-mail: george.rodrigues@lhsc.on.ca [London Health Sciences Centre, London, Ontario (Canada); Oberije, Cary [MAASTRO Clinic, Maastricht (Netherlands); Senan, Suresh [VU University Medical Center, Amsterdam (Netherlands); Tsujino, Kayoko [Hyogo Cancer Center, Akashi (Japan); Wiersma, Terry [MAASTRO Clinic, Maastricht (Netherlands); Moreno-Jimenez, Marta [Universidad de Navarra, Pamplona (Spain); Kim, Tae Hyun [National Cancer Center, Goyang-si, Gy eonggi (Korea, Republic of); Marks, Lawrence B. [University of North Carolina, Chapel Hill, North Carolina (United States); Rengan, Ramesh [University of Washington, Seattle, Washington (United States); De Petris, Luigi [Karolinska University Hospital, Stockholm (Sweden); Ramella, Sara [Campus Bio-Medico University, Rome (Italy); DeRuyck, Kim [Ghent University, Ghent (Belgium); De Dios, Núria Rodriguez [Universidad Pompeu Fabra, Barcelona (Spain); Warner, Andrew [London Health Sciences Centre, London, Ontario (Canada); Bradley, Jeffrey D. [Washington University School of Medicine, St. Louis, Missouri (United States); Palma, David A. [London Health Sciences Centre, London, Ontario (Canada)

    2015-01-01

    Purpose: The clinical benefits and risks of dose escalation (DE) for stage III non–small-cell lung cancer (NSCLC) remain uncertain despite the results from Radiation Therapy Oncology Group (RTOG) protocol 0617. There is significant heterogeneity of practice, with many clinicians prescribing intermediate dose levels between the 0617 study arms of 60 and 74 Gy. This study investigated whether this strategy is associated with any survival benefits/risks by analyzing a large multi-institutional database. Methods and Materials: An individual patient database of stage III NSCLC patients treated with radical intent concurrent chemoradiation therapy was created (13 institutions, n=1274 patients). Patients were divided into 2 groups based on tumor Biological Effective Dose at 10 Gy (BED 10): those receiving standard dose (SD; n=552), consisting of 72Gy ≤ BED 10 ≤ 76.8 Gy (eg 60-64 Gy/30-32 fractions [fr]), and those receiving intermediate dose (ID; n=497), consisting of 76.8Gy < BED 10 < 100.8 Gy (eg >64 Gy/32 fr and <74 Gy/37 fr), with lower-dose patients (n=225) excluded from consideration. Patients were then matched using propensity scores, leading to 2 matched groups of 196 patients. Outcomes were compared using various statistics including interquartile range (IQR), Kaplan-Meier curves, and adjusted Cox regression analysis. Results: Matched groups were found to be balanced except for N stage (more N3 disease in SD), median treatment year (SD in 2003; ID in 2007), platinum and taxane chemotherapy (SD in 28%; ID in 39%), and median follow-up (SD were 89 months; ID were 40 months). Median dose fractionation was 60 Gy/30 fr in SD (BED 10 IQR: 72.0-75.5 Gy) and 66 Gy/33 fr (BED 10 IQR: 78.6-79.2 Gy) in ID. Survival curves for SD and ID matched cohorts were statistically similar (P=.27); however, a nonstatistically significant trend toward better survival for ID was observed after 15 months (median survival SD: 19.3 months; ID: 21.0

  19. Using Fluorodeoxyglucose Positron Emission Tomography to Assess Tumor Volume During Radiotherapy for Non-Small-Cell Lung Cancer and Its Potential Impact on Adaptive Dose Escalation and Normal Tissue Sparing

    International Nuclear Information System (INIS)

    Purpose: To quantify changes in fluorodeoxyglucose (FDG)-avid tumor volume on positron emission tomography/computed tomography (PET/CT) during the course of radiation therapy and examine its potential use in adaptive radiotherapy for tumor dose escalation or normal tissue sparing in patients with non-small-cell lung cancer (NSCLC). Methods and Materials: As part of a pilot study, patients with Stage I-III NSCLC underwent FDG-PET/CT before radiotherapy (RT) and in mid-RT (after 40-50 Gy). Gross tumor volumes were contoured on CT and PET scans obtained before and during RT. Three-dimensional conformal RT plans were generated for each patient, first using only pretreatment CT scans. Mid-RT PET volumes were then used to design boost fields. Results: Fourteen patients with FDG-avid tumors were assessed. Two patients had a complete metabolic response, and 2 patients had slightly increased FDG uptake in the adjacent lung tissue. Mid-RT PET scans were useful in the 10 remaining patients. Mean decreases in CT and PET tumor volumes were 26% (range, +15% to -75%) and 44% (range, +10% to -100%), respectively. Designing boosts based on mid-RT PET allowed for a meaningful dose escalation of 30-102 Gy (mean, 58 Gy) or a reduction in normal tissue complication probability (NTCP) of 0.4-3% (mean, 2%) in 5 of 6 patients with smaller yet residual tumor volumes. Conclusions: Tumor metabolic activity and volume can change significantly after 40-50 Gy of RT. Using mid-RT PET volumes, tumor dose can be significantly escalated or NTCP reduced. Clinical studies evaluating patient outcome after PET-based adaptive RT are ongoing

  20. α-Synuclein Aggregation and Ser-129 Phosphorylation-dependent Cell Death in Oligodendroglial Cells*S⃞

    OpenAIRE

    Kragh, Christine L.; Lund, Louise B.; Febbraro, Fabia; Hansen, Hanne D.; Gai, Wei-Ping; El-Agnaf, Omar; Richter-Landsberg, Christiane; Jensen, Poul Henning

    2009-01-01

    Multiple system atrophy is a neurodegenerative disorder characterized by accumulation of aggregated Ser-129-phosphorylated α-synuclein in oligodendrocytes. p25α is an oligodendroglial protein that potently stimulates α-synuclein aggregation in vitro. To model multiple system atrophy, we coexpressed human p25α and α-synuclein in the rat oligodendroglial cell line OLN-93 and observed a cellular response characterized by a fast retraction of microtubules from the cellular...

  1. Sequential development of apical-basal and planar polarities in aggregating epitheliomuscular cells of Hydra.

    Science.gov (United States)

    Seybold, Anna; Salvenmoser, Willi; Hobmayer, Bert

    2016-04-01

    Apical-basal and planar cell polarities are hallmarks of metazoan epithelia required to separate internal and external environments and to regulate trans- and intracellular transport, cytoskeletal organization, and morphogenesis. Mechanisms of cell polarization have been intensively studied in bilaterian model organisms, particularly in early embryos and cultured cells, while cell polarity in pre-bilaterian tissues is poorly understood. Here, we have studied apical-basal and planar polarization in regenerating (aggregating) clusters of epitheliomuscular cells of Hydra, a simple representative of the ancestral, pre-bilaterian phylum Cnidaria. Immediately after dissociation, single epitheliomuscular cells do not exhibit cellular polarity, but they polarize de novo during aggregation. Reestablishment of the Hydra-specific epithelial bilayer is a result of short-range cell sorting. In the early phase of aggregation, apical-basal polarization starts with an enlargement of the epithelial apical-basal diameter and by the development of belt-like apical septate junctions. Specification of the basal pole of epithelial cells occurs shortly later and is linked to synthesis of mesoglea, development of hemidesmosome-like junctions, and formation of desmosome-like junctions connecting the basal myonemes of neighbouring cells. Planar polarization starts, while apical-basal polarization is already ongoing. It is executed gradually starting with cell-autonomous formation, parallelization, and condensation of myonemes at the basal end of each epithelial cell and continuing with a final planar alignment of epitheliomuscular cells at the tissue level. Our findings reveal that epithelial polarization in Hydra aggregates occurs in defined steps well accessible by histological and ultrastructural techniques and they will provide a basis for future molecular studies. PMID:26921448

  2. Measurement of interaction forces between red blood cells in aggregates by optical tweezers

    Energy Technology Data Exchange (ETDEWEB)

    Maklygin, A Yu; Priezzhev, A V; Karmenian, A; Nikitin, Sergei Yu; Obolenskii, I S; Lugovtsov, Andrei E; Kisun Li

    2012-06-30

    We have fabricated double-beam optical tweezers and demonstrated the possibility of their use for measuring the interaction forces between red blood cells (erythrocytes). It has been established experimentally that prolonged trapping of red blood cells in a tightly focused laser beam does not cause any visible changes in their shape or size. We have measured the interaction between red blood cells in the aggregate, deformed by optical tweezers.

  3. Effects of Erythrocyte Deformability and Aggregation on the Cell Free Layer and Apparent Viscosity of Microscopic Blood Flows

    OpenAIRE

    Zhang, Junfeng; Johnson, Paul C.; Popel, Aleksander S.

    2009-01-01

    Concentrated erythrocyte (i.e., red blood cell) suspensions flowing in microchannels have been simulated with an immersed-boundary lattice Boltzmann algorithm, to examine the cell layer development process and the effects of cell deformability and aggregation on hemodynamic and hemorheological behaviors. The cells are modeled as two-dimensional deformable biconcave capsules and experimentally measured cell properties have been utilized. The aggregation among cells is modeled by a Morse potent...

  4. Experiment on aggregation of red cells under microgravity on STS 51-C

    Science.gov (United States)

    Dintenfass, L.; Osman, P.; Maguire, B.; Jedrzejczyk, H.

    Kinetics and morphology of aggregation of red cells were studied using automatic slit-capillary photo-viscometers, one situated on the middeck of the space shuttle `Discovery', and the other in the ground laboratory at KSC. Experiments were run simultaneously, blood samples being adjusted to haematocrit of 0.30 using native plasma, at temp. of 25°C, and anticoagulated by EDTA. Donors included patients with myocardial infarction, insulin-dependent diabetes, hyperlipidaemia and hypertension. Macro and microphotographs were obtained during flow and statis. There was a striking difference in the morphology of aggregates formed in space and on the ground. Aggregates formed under zero gravity showed rouleaux formation, while the same blood samples showed severe clumping on the ground, in all patients blood. Normal blood showed rouleaux on the ground, but a random swarm-like pattern in space. The shape of the red cells remained normal under zero gravity.

  5. Moving Walkways, Escalators, and Elevators

    OpenAIRE

    Cardinal, J.; Collette, S; Hurtado, F.; Langerman, S.; Palop, B.

    2007-01-01

    We study a simple geometric model of transportation facility that consists of two points between which the travel speed is high. This elementary definition can model shuttle services, tunnels, bridges, teleportation devices, escalators or moving walkways. The travel time between a pair of points is defined as a time distance, in such a way that a customer uses the transportation facility only if it is helpful. We give algorithms for finding the optimal location of such a transportation facili...

  6. Cluster-cluster aggregation with particle replication and chemotaxy: a simple model for the growth of animal cells in culture

    OpenAIRE

    Alves, S. G.; M. L. Martins

    2010-01-01

    Aggregation of animal cells in culture comprises a series of motility, collision and adhesion processes of basic relevance for tissue engineering, bioseparations, oncology research and \\textit{in vitro} drug testing. In the present paper, a cluster-cluster aggregation model with stochastic particle replication and chemotactically driven motility is investigated as a model for the growth of animal cells in culture. The focus is on the scaling laws governing the aggregation kinetics. Our simula...

  7. Cell aggregation of Pseudomonas aeruginosa strain PAO1 as an energy-dependent stress response during growth sodium dodecyl sulfate

    OpenAIRE

    Klebensberger, Janosch; Rui, Oliver; Fritz, Eva; Schink, Bernhard; Philipp, Bodo

    2006-01-01

    Pseudomonas aeruginosa strain PAO1 grew with the detergent sodium dodecyl sulfate (SDS). The growth started with the formation of macroscopic cell aggregates which consisted of respiring cells embedded in an extracellular matrix composed of acidic polysaccharides and DNA. Damaged and uncultivable cells accumulated in these aggregates compared to those cells that remained suspended. We investigated the response of suspended cells to SDS under different conditions. At high energy supply, the ce...

  8. Freely Suspended Cellular “Backpacks” Lead to Cell Aggregate Self-Assembly

    OpenAIRE

    Swiston, Albert J., Jr.; Gilbert, Jonathan B.; Irvine, Darrell J.; Cohen, Robert E; Rubner, Michael F.

    2010-01-01

    Cellular “backpacks” are a new type of anisotropic, nanoscale thickness microparticle that may be attached to the surface of living cells creating a “bio-hybrid” material. Previous work has shown that these backpacks do not impair cell viability or native functions such as migration in a B and T cell line, respectively. In the current work, we show that backpacks, when added to a cell suspension, assemble cells into aggregates of reproducible size. We investigate the efficiency of backpack−ce...

  9. Analysis of aggregated cell–cell statistical distances within pathways unveils therapeutic-resistance mechanisms in circulating tumor cells

    Science.gov (United States)

    Schissler, A. Grant; Li, Qike; Chen, James L.; Kenost, Colleen; Achour, Ikbel; Billheimer, D. Dean; Li, Haiquan; Piegorsch, Walter W.; Lussier, Yves A.

    2016-01-01

    Motivation: As ‘omics’ biotechnologies accelerate the capability to contrast a myriad of molecular measurements from a single cell, they also exacerbate current analytical limitations for detecting meaningful single-cell dysregulations. Moreover, mRNA expression alone lacks functional interpretation, limiting opportunities for translation of single-cell transcriptomic insights to precision medicine. Lastly, most single-cell RNA-sequencing analytic approaches are not designed to investigate small populations of cells such as circulating tumor cells shed from solid tumors and isolated from patient blood samples. Results: In response to these characteristics and limitations in current single-cell RNA-sequencing methodology, we introduce an analytic framework that models transcriptome dynamics through the analysis of aggregated cell–cell statistical distances within biomolecular pathways. Cell–cell statistical distances are calculated from pathway mRNA fold changes between two cells. Within an elaborate case study of circulating tumor cells derived from prostate cancer patients, we develop analytic methods of aggregated distances to identify five differentially expressed pathways associated to therapeutic resistance. Our aggregation analyses perform comparably with Gene Set Enrichment Analysis and better than differentially expressed genes followed by gene set enrichment. However, these methods were not designed to inform on differential pathway expression for a single cell. As such, our framework culminates with the novel aggregation method, cell-centric statistics (CCS). CCS quantifies the effect size and significance of differentially expressed pathways for a single cell of interest. Improved rose plots of differentially expressed pathways in each cell highlight the utility of CCS for therapeutic decision-making. Availability and implementation: http://www.lussierlab.org/publications/CCS/ Contact: yves@email.arizona.edu or piegorsch

  10. Highly Sensitive Detection of Red Blood Cell Aggregation with Ultrasonic Peak Frequency

    Science.gov (United States)

    Sato, Takayuki; Tojo, Hiroyuki; Watanabe, Yasuaki

    2013-07-01

    A novel technique of detecting the peak frequency of an ultrasonic reflection spectrum was proposed, with the aim of enhancing the sensitivity and accuracy of estimating the aggregation size of red blood cells (RBCs). Peak frequencies for stagnant and running suspensions prepared with monodisperse particles of graphite and acryl that were used to mimic aggregated RBCs were acquired. As a result, the relationships between particle diameter and peak frequency, which were independent of the material of the particles and flow rate, were obtained. For bidisperse samples, i.e., mixtures of two different sizes of particle samples, quantitative relationships corresponding to changes in the mixing ratio were observed.

  11. Kinetics of red blood cell aggregation: an example of geometric polymerization

    Energy Technology Data Exchange (ETDEWEB)

    Perelson, A.S.; Samsel, R.W.

    1984-04-02

    The kinetics of the process by which red blood cells aggregate into long cylindrical, and sometimes branched, structures called rouleaux is studied within the framework of both reversible and irreversible addition and condensation polymerization reactions. However, unlike usual polymer kinetics, here we take into account the geometry of the subunits and the geometry of the growing structure. Geometric factors such as the amount of reactive wall area influence the probability of branching and hence the final shape of the aggregate. The inclusion of loop formation reactions is shown to be crucial in obtaining physically realistic equilibrium solutions of the kinetic equations. 11 references, 3 figures.

  12. MODELS FOR MOUSE CHIMERA PRODUCTION: AGGREGATION OF ES CELLS WITH CLEAVAGE STAGE EMBRYOS

    OpenAIRE

    CLAUDIA STANCA; V.B. CÂRSTEA; DANIELA ILIE; ELEN GOCZA; I. VINTILĂ

    2007-01-01

    In a mutant ES cells↔ wild-type embryo chimera, ES cells behave more like epiblastcells. They can contribute to the primitive ectoderm layers, which give rise to all theembryonic tissues and some extraembryonic tissues (Beddington and Robertson,1989), but not to trophectoderm or primitive endoderm. Using transgenic ES celllines, aggregated with cleavage stage host embryo, ES cells can integrate randomlyin the embryo proper. If they will be take part in the formation of ICM (inner cellmass), i...

  13. Effect of red blood cell aggregation and sedimentation on optical coherence tomography signals from blood samples

    International Nuclear Information System (INIS)

    In this work, Monte Carlo simulation is used to obtain model optical coherence tomography (OCT) signals from a horizontally orientated blood layer at different stages of red blood cell (RBC) aggregation and sedimentation processes. The parameters for aggregating and sedimenting blood cells were chosen based on the data available from the literature and our earlier experimental studies. We consider two different cases: a suspension of washed RBCs in physiological solution (where aggregation does not take place) and RBCs in blood plasma (which provides necessary conditions for aggregation). Good agreement of the simulation results with the available experimental data shows that the chosen optical parameters are reasonable. The dependence of the numbers of photons contributing to the OCT signal on the number of experienced scattering events was analysed for each simulated signal. It was shown that the maxima of these dependences correspond to the peaks in the OCT signals related to the interfaces between the layers of blood plasma and blood cells. Their positions can be calculated from the optical thicknesses of the layers, and the absorption and scattering coefficients of the media

  14. Confocal fluorescence anisotropy and FRAP imaging of α-synuclein amyloid aggregates in living cells.

    Directory of Open Access Journals (Sweden)

    M Julia Roberti

    Full Text Available We assessed the intracellular association states of the Parkinson's disease related protein α-synuclein (AS in living cells by transfection with a functional recombinant mutant protein (AS-C4 bearing a tetracysteine tag binding the fluorogenic biarsenical ligands FlAsH and ReAsH, The aggregation states of AS-C4 were assessed by in situ microscopy of molecular translational mobility with FRAP (fluorescence recovery after photobleaching and of local molecular density with confocal fluorescence anisotropy (CFA. FRAP recovery was quantitative and rapid in regions of free protein, whereas AS in larger aggregates was>80% immobile. A small 16% recovery characterized by an apparent diffusion constant of 0.03-0.04 µm(2/s was attributed to the dynamics of smaller, associated forms of AS-C4 and the exchange of mobile species with the larger immobile aggregates. By CFA, the larger aggregates exhibited high brightness and very low anisotropy, consistent with homoFRET between closely packed AS, for which a Förster distance (R(o of 5.3 nm was calculated. Other bright regions had high anisotropy values, close to that of monomeric AS, and indicative of membrane-associated protein with both low mobility and low degree of association. The anisotropy-fluorescence intensity correlations also revealed regions of free protein or of small aggregates, undetectable by conventional fluorescence imaging alone. The combined strategy (FRAP+CFA provides a highly sensitive means for elucidating both the dynamics and structural features of protein aggregates and other intracellular complexes in living cells, and can be extended to other amyloid systems and to drug screening protocols.

  15. Aggregation Substance Increases Adherence and Internalization, but Not Translocation, of Enterococcus faecalis through Different Intestinal Epithelial Cells In Vitro

    OpenAIRE

    Sartingen, S.; Rozdzinski, E; Muscholl-Silberhorn, A.; Marre, R

    2000-01-01

    The aggregation substance of Enterococcus faecalis increased bacterial adherence to and internalization by epithelial cells originating from the colon and duodenum but not by cells derived from the ileum. However, enterococcal translocation through monolayers of intestinal epithelium was not observed.

  16. Protein carbonylation, protein aggregation and neuronal cell death in a murine model of multiple sclerosis

    Science.gov (United States)

    Dasgupta, Anushka

    Many studies have suggested that oxidative stress plays an important role in the pathophysiology of both multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Yet, the mechanism by which oxidative stress leads to tissue damage in these disorders is unclear. Recent work from our laboratory has revealed that protein carbonylation, a major oxidative modification caused by severe and/or chronic oxidative stress conditions, is elevated in MS and EAE. Furthermore, protein carbonylation has been shown to alter protein structure leading to misfolding/aggregation. These findings prompted me to hypothesize that carbonylated proteins, formed as a consequence of oxidative stress and/or decreased proteasomal activity, promote protein aggregation to mediate neuronal apoptosis in vitro and in EAE. To test this novel hypothesis, I first characterized protein carbonylation, protein aggregation and apoptosis along the spinal cord during the course of myelin-oligodendrocyte glycoprotein (MOG)35-55 peptide-induced EAE in C57BL/6 mice [Chapter 2]. The results show that carbonylated proteins accumulate throughout the course of the disease, albeit by different mechanisms: increased oxidative stress in acute EAE and decreased proteasomal activity in chronic EAE. I discovered not only that there is a temporal correlation between protein carbonylation and apoptosis but also that carbonyl levels are significantly higher in apoptotic cells. A high number of juxta-nuclear and cytoplasmic protein aggregates containing the majority of the oxidized proteins are also present during the course of EAE, which seems to be due to reduced autophagy. In chapter 3, I show that when gluthathione levels are reduced to those in EAE spinal cord, both neuron-like PC12 (nPC12) cells and primary neuronal cultures accumulate carbonylated proteins and undergo cell death (both by necrosis and apoptosis). Immunocytochemical and biochemical studies also revealed a temporal

  17. Effect of erythrocyte aggregation and flow rate on cell-free layer formation in arterioles

    OpenAIRE

    Ong, Peng Kai; Namgung, Bumseok; Johnson, Paul C.; Kim, Sangho

    2010-01-01

    Formation of a cell-free layer is an important dynamic feature of microcirculatory blood flow, which can be influenced by rheological parameters, such as red blood cell aggregation and flow rate. In this study, we investigate the effect of these two rheological parameters on cell-free layer characteristics in the arterioles (20–60 μm inner diameter). For the first time, we provide here the detailed temporal information of the arteriolar cell-free layer in various rheological conditions to bet...

  18. Moving Walkways, Escalators, and Elevators

    CERN Document Server

    Cardinal, J; Hurtado, F; Langerman, S; Palop, B

    2007-01-01

    We study a simple geometric model of transportation facility that consists of two points between which the travel speed is high. This elementary definition can model shuttle services, tunnels, bridges, teleportation devices, escalators or moving walkways. The travel time between a pair of points is defined as a time distance, in such a way that a customer uses the transportation facility only if it is helpful. We give algorithms for finding the optimal location of such a transportation facility, where optimality is defined with respect to the maximum travel time between two points in a given set.

  19. A laser flow aggregometer for measurement of white blood cell and platelet aggregation

    International Nuclear Information System (INIS)

    The measurement of aggregation of white blood cells and platelets is important in understanding cardiovascular disease. A new aggregometer has been developed, based on a laser flow cytometer. Pulses detected using a high speed photodiode are acquired to a computer and analysed. Tests based on separated white cells, platelets and whole blood samples have been carried out to evaluate this system. Results show that the laser flow cytometer system has a much better resolution and wider dynamic range than existing electronic flow cytometer instruments. As a result, more details of platelet and white blood cell aggregation profiles can be obtained. The new aggregometer is now being used in clinical trials on patients with vascular disease, for comparison with commercial systems. (author)

  20. In vitro spatially organizing the differentiation in individual multicellular stem cell aggregates.

    Science.gov (United States)

    Qi, Hao; Huang, Guoyou; Han, Yu Long; Lin, Wang; Li, Xiujun; Wang, Shuqi; Lu, Tian Jian; Xu, Feng

    2016-01-01

    With significant potential as a robust source to produce specific somatic cells for regenerative medicine, stem cells have attracted increasing attention from both academia and government. In vivo, stem cell differentiation is a process under complicated regulations to precisely build tissue with unique spatial structures. Since multicellular spheroidal aggregates of stem cells, commonly called as embryoid bodies (EBs), are considered to be capable of recapitulating the events in early stage of embryonic development, a variety of methods have been developed to form EBs in vitro for studying differentiation of embryonic stem cells. The regulation of stem cell differentiation is crucial in directing stem cells to build tissue with the correct spatial architecture for specific functions. However, stem cells within the three-dimensional multicellular aggregates undergo differentiation in a less unpredictable and spatially controlled manner in vitro than in vivo. Recently, various microengineering technologies have been developed to manipulate stem cells in vitro in a spatially controlled manner. Herein, we take the spotlight on these technologies and researches that bring us the new potential for manipulation of stem cells for specific purposes. PMID:25025275

  1. Cell Surface Binding and Internalization of Aβ Modulated by Degree of Aggregation

    Directory of Open Access Journals (Sweden)

    David A. Bateman

    2011-01-01

    Full Text Available The amyloid peptides, Aβ40 and Aβ42, are generated through endoproteolytic cleavage of the amyloid precursor protein. Here we have developed a model to investigate the interaction of living cells with various forms of aggregated Aβ40/42. After incubation at endosomal pH 6, we observed a variety of Aβ conformations after 3 (Aβ3, 24 (Aβ24, and 90 hours (Aβ90. Both Aβ4224 and Aβ4024 were observed to rapidly bind and internalize into differentiated PC12 cells, leading to accumulation in the lysosome. In contrast, Aβ40/4290 were both found to only weakly associate with cells, but were observed as the most aggregated using dynamic light scattering and thioflavin-T. Internalization of Aβ40/4224 was inhibited with treatment of monodansylcadaverine, an endocytosis inhibitor. These studies indicate that the ability of Aβ40/42 to bind and internalize into living cells increases with degree of aggregation until it reaches a maximum beyond which its ability to interact with cells diminishes drastically.

  2. Hydrogel Microwell Arrays Allow the Assessment of Protease-Associated Enhancement of Cancer Cell Aggregation and Survival

    Directory of Open Access Journals (Sweden)

    Dietmar W. Hutmacher

    2013-08-01

    Full Text Available Current routine cell culture techniques are only poorly suited to capture the physiological complexity of tumor microenvironments, wherein tumor cell function is affected by intricate three-dimensional (3D, integrin-dependent cell-cell and cell-extracellular matrix (ECM interactions. 3D cell cultures allow the investigation of cancer-associated proteases like kallikreins as they degrade ECM proteins and alter integrin signaling, promoting malignant cell behaviors. Here, we employed a hydrogel microwell array platform to probe using a high-throughput mode how ovarian cancer cell aggregates of defined size form and survive in response to the expression of kallikreins and treatment with paclitaxel, by performing microscopic, quantitative image, gene and protein analyses dependent on the varying microwell and aggregate sizes. Paclitaxel treatment increased aggregate formation and survival of kallikrein-expressing cancer cells and levels of integrins and integrin-related factors. Cancer cell aggregate formation was improved with increasing aggregate size, thereby reducing cell death and enhancing integrin expression upon paclitaxel treatment. Therefore, hydrogel microwell arrays are a powerful tool to screen the viability of cancer cell aggregates upon modulation of protease expression, integrin engagement and anti-cancer treatment providing a micro-scaled yet high-throughput technique to assess malignant progression and drug-resistance.

  3. Imaging Alzheimer's disease-related protein aggregates in human cells using a selenium label

    International Nuclear Information System (INIS)

    The aberrant folding and subsequent aggregation of proteins and peptides is associated with a range of pathological conditions from the systemic amyloidoses to neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. While this link is well established there is a lack of understanding of the exact role protein aggregates play in disease pathogenesis. Part of the reason for this is that it has proved extremely challenging to characterise the localisation and structure of amyloid fibrils within the cellular environment due to a lack of contrast between the carbon rich protein aggregates and the carbon rich cell. We report a novel method for visualising Alzheimer's disease-related amyloid fibrils inside human cells without the use of invasive or unreliable stains or tags. The naturally occurring sulfur atom in the amyloid-β peptide is replaced with a selenium atom, a heavier element in the same group of the periodic table of elements. Using high angle annular dark field (HAADF) in a scanning transmission electron microscopy (STEM) the selenium-labelled aggregates can be identified within the cellular environment.

  4. Aggregates of plasmonic nanoparticles for broadband light trapping in dye-sensitized solar cells

    International Nuclear Information System (INIS)

    Metallic nanoparticles (NPs) have not been effective in improving the overall performance of the cells with micrometer-thick absorbing layers mainly due to the parasitic optical dissipation in the metal. Here, using both experiment and theory, we demonstrate that aggregates of metallic NPs enhance the light absorption of dye-sensitized solar cells of a few micrometer-thick light absorbing layers. The composite electrode containing the optimal concentration of 5 wt% Au@SiO2 aggregates shows the enhancement of 80% and 52% in external quantum efficiency and photocurrent density, respectively. The superior performance of the aggregates relative to NP is attributed to their larger scattering efficiency using full-wave optical simulations. This is further confirmed by optical spectroscopic measurements showing that a large fraction of the incident light couples into the diffused components because of the presence of these metallic aggregates. The optical absorption enhancement is broadband and it is particularly strong at wavelengths larger than 680 nm where the optical absorption of dye molecules is weak. (paper)

  5. Production Pattern of Ajmalicine in Catharanthus roseus (L.) G. Don. Cell Aggregates Culture in the Airlift Bioreactor

    OpenAIRE

    RIZKITA RACHMI ESYANTI; AIDA MUSPIAH

    2006-01-01

    A research has been conducted to optimize the rate of aeration and initial weight of cell aggregates in the production of ajmalicine in Catharanthus roseus cell culture in airlift bioreactor. Catharanthus roseus culture were grown in Zenk medium with the addition of 2.50 x 10-6 M naphthalene acetic acid (NAA) and 10-5 M benzyl amino purine (BAP). Cell aggregates were sub-cultured two times before transferring 20 and 30 g/fw of cell aggregates into bioreactor, respectively, and aerated with th...

  6. Aggregation-Induced Emission Luminogen-Embedded Silica Nanoparticles Containing DNA Aptamers for Targeted Cell Imaging.

    Science.gov (United States)

    Wang, Xiaoyan; Song, Panshu; Peng, Lu; Tong, Aijun; Xiang, Yu

    2016-01-13

    Conventional fluorophores usually undergo aggregation-caused quenching (ACQ), which limits the loading amount of these fluorophores in nanoparticles for bright fluorescence imaging. On the contrary, fluorophores with aggregation-induced emission (AIE) characteristics are strongly fluorescent in their aggregate states and have been an ideal platform for developing highly fluorescent nanomaterials, such as fluorescent silica nanoparticles (FSNPs). In this work, AIE luminogens based on salicylaldehyde hydrazones were embedded in silica nanoparticles through a facile noncovalent approach, which afforded AIE-FSNPs emitting much brighter fluorescence than that of some commercial fluorescein-doped silica and polystyrene nanoparticles. These AIE-FSNPs displaying multiple fluorescence colors were fabricated by a general method, and they underwent much less fluorescence variation due to environmental pH changes compared with fluorescein-hybridized FSNPs. In addition, a DNA aptamer specific to nucleolin was functionalized on the surface of AIE-FSNPs for targeted cell imaging. Fluorescent microscopy and flow cytometry studies both revealed highly selective fluorescence staining of MCF-7 (a cancer cell line with nucleolin overexpression) over MCF-10A (normal) cells by the aptamer-functionalized AIE-FSNPs. The fluorescence imaging in different color channels was achieved using AIE-FSNPs containing each of the AIE luminogens, as well as photoactivatable fluorescent imaging of target cells by the caged AIE fluorophore. PMID:26653325

  7. Ultrasound characterization of red blood cell aggregation with intervening attenuating tissue-mimicking phantoms

    OpenAIRE

    Franceschini, Emilie; Yu, François,; Destrempes, François; Cloutier, Guy

    2010-01-01

    The analysis of the ultrasonic frequency-dependent backscatter coefficient of aggregating red blood cells reveals information about blood structural properties. The difficulty in applying this technique \\emph{in vivo} is due to the frequency-dependent attenuation caused by intervening tissue layers that distorts the spectral content of signals backscattered by blood. An optimization method is proposed to simultaneously estimate tissue attenuation and blood structure properties, and was termed...

  8. Modeling multivalent ligand-receptor interactions with steric constraints on configurations of cell surface receptor aggregates

    Energy Technology Data Exchange (ETDEWEB)

    Monine, Michael [Los Alamos National Laboratory; Posner, Richard [TRANSLATION GENOMICS RESAEARCH INSTITUTE; Savage, Paul [BYU; Faeder, James [UNIV OF PITTSBURGH; Hlavacek, William S [UNM

    2008-01-01

    Signal transduction generally involves multivalent protein-protein interactions, which can produce various protein complexes and post-translational modifications. The reaction networks that characterize these interactions tend to be so large as to challenge conventional simulation procedures. To address this challenge, a kinetic Monte Carlo (KMC) method has been developed that can take advantage of a model specification in terms of reaction rules for molecular interactions. A set of rules implicitly defines the reactions that can occur as a result of the interactions represented by the rules. With the rule-based KMC method, explicit generation of the underlying chemical reaction network implied by rules is avoided. Here, we apply and extend this method to characterize the interactions of a trivalent ligand with a bivalent cell-surface receptor. This system is also studied experimentally. We consider the following kinetic models: an equivalent-site model, an extension of this model, which takes into account steric constraints on the configurations of receptor aggregates, and finally, a model that accounts for cyclic receptor aggregates. Simulation results for the equivalent-site model are consistent with an equilibrium continuum model. Using these models, we investigate the effects of steric constraints and the formation of cyclic aggregates on the kinetics and equilibria of small and large aggregate formation and the percolation phase transition that occurs in this system.

  9. Conformational Analysis of Misfolded Protein Aggregation by FRET and Live-Cell Imaging Techniques

    Directory of Open Access Journals (Sweden)

    Akira Kitamura

    2015-03-01

    Full Text Available Cellular homeostasis is maintained by several types of protein machinery, including molecular chaperones and proteolysis systems. Dysregulation of the proteome disrupts homeostasis in cells, tissues, and the organism as a whole, and has been hypothesized to cause neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS and Huntington’s disease (HD. A hallmark of neurodegenerative disorders is formation of ubiquitin-positive inclusion bodies in neurons, suggesting that the aggregation process of misfolded proteins changes during disease progression. Hence, high-throughput determination of soluble oligomers during the aggregation process, as well as the conformation of sequestered proteins in inclusion bodies, is essential for elucidation of physiological regulation mechanism and drug discovery in this field. To elucidate the interaction, accumulation, and conformation of aggregation-prone proteins, in situ spectroscopic imaging techniques, such as Förster/fluorescence resonance energy transfer (FRET, fluorescence correlation spectroscopy (FCS, and bimolecular fluorescence complementation (BiFC have been employed. Here, we summarize recent reports in which these techniques were applied to the analysis of aggregation-prone proteins (in particular their dimerization, interactions, and conformational changes, and describe several fluorescent indicators used for real-time observation of physiological states related to proteostasis.

  10. Modeling and analysis of ultrasound backscattering by spherical aggregates and rouleaux of red blood cells.

    Science.gov (United States)

    Teh, B G; Cloutier, G

    2000-01-01

    The present study concerns the modeling and analysis of ultrasound backscattering by red blood cell (RBC) aggregates, which under pathological conditions play a significant role in the rheology of blood within human vessels. A theoretical model based on the convolution between a tissue matrix and a point spread function, representing, respectively, the RBC aggregates and the characteristics of the ultrasound system, was used to examine the influence of the scatterer shape and size on the backscattered power. Both scatterers in the form of clumps of RBC aggregates and rouleaux were modeled. For all simulations, the hematocrit was kept constant at 10%, the ultrasound frequency was 10 MHz, the insonification angle was varied from 0 to 90 degrees , and the scatterer size (diameter for clumps and length for rouleaux) ranged from 4 mum to 120 mum. Under Rayleigh scattering by assuming a Poisson distribution of scatterers in space, the ultrasound backscattered power increased linearly with the particle volume. For non-Rayleigh scatterers, the intensity of the echoes diminished as the scatterer volume increased, with the exception of rouleaux at an angle of 90 degrees . As expected, the backscattered power was angularly dependent for anisotropic particles (rouleaux). The ultrasound backscattered power did not always increase with the size of the aggregates, especially when they were no longer Rayleigh scatterers. In the case of rouleaux, the anisotropy of the backscattered power is emphasized in the non-Rayleigh region. PMID:18238637

  11. Optimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling.

    KAUST Repository

    Chapman, Lloyd A C

    2014-08-26

    The need for efficient and controlled expansion of cell populations is paramount in tissue engineering. Hollow fibre bioreactors (HFBs) have the potential to meet this need, but only with improved understanding of how operating conditions and cell seeding strategy affect cell proliferation in the bioreactor. This study is designed to assess the effects of two key operating parameters (the flow rate of culture medium into the fibre lumen and the fluid pressure imposed at the lumen outlet), together with the cell seeding distribution, on cell population growth in a single-fibre HFB. This is achieved using mathematical modelling and numerical methods to simulate the growth of cell aggregates along the outer surface of the fibre in response to the local oxygen concentration and fluid shear stress. The oxygen delivery to the cell aggregates and the fluid shear stress increase as the flow rate and pressure imposed at the lumen outlet are increased. Although the increased oxygen delivery promotes growth, the higher fluid shear stress can lead to cell death. For a given cell type and initial aggregate distribution, the operating parameters that give the most rapid overall growth can be identified from simulations. For example, when aggregates of rat cardiomyocytes that can tolerate shear stresses of up to 0:05 Pa are evenly distributed along the fibre, the inlet flow rate and outlet pressure that maximise the overall growth rate are predicted to be in the ranges 2.75 x 10(-5) m(2) s(-1) to 3 x 10(-5) m(2) s(-1) (equivalent to 2.07 ml min(-1) to 2.26 ml min(-1)) and 1.077 x 10(5) Pa to 1.083 x 10(5) Pa (or 15.6 psi to 15.7 psi) respectively. The combined effects of the seeding distribution and flow on the growth are also investigated and the optimal conditions for growth found to depend on the shear tolerance and oxygen demands of the cells.

  12. Calming an escalated psychiatric milieu.

    Science.gov (United States)

    Delaney, K R

    1994-01-01

    On inpatient psychiatric units, nurses control the tone, pace, and activity level of the environment. But under the influence of factors such as high patient acuity and negative group contagion, a milieu can become unacceptably loud and chaotic. A volatile milieu is a potentially dangerous environment because patients' anxiety and agitation can quickly lead to acting out and aggression. This article focuses on how nurses can regain control of a milieu spiralling into chaos by tightening the structure of the routine, anticipating potential problems, and maintaining a confident calm manner. The charge nurse orchestrates the staff group's response to escalation through detailed planning, decisive interventions, and strategic use of every available resource. PMID:7697316

  13. Cell aggregation optimizes the differentiation of human ESCs and iPSCs into pancreatic bud-like progenitor cells

    Directory of Open Access Journals (Sweden)

    Taro Toyoda

    2015-03-01

    Full Text Available Embryonic pancreatic bud cells, the earliest pancreas-committed cells, generated from human embryonic stem cells (hESCs and induced pluripotent stem cells (hiPSCs have been shown to differentiate into mature pancreatic β-cells in vivo, indicating the feasibility of hESC/iPSC-based cell therapy for diabetes. However, the key factors required for the differentiation of these cells into pancreatic bud cells are incompletely understood. The purpose of this study was to establish culture conditions that efficiently induce PDX1+NKX6.1+ pancreatic bud cells from hESCs/iPSCs. We differentiated a hESC line, KhES-3, into pancreatic lineages with a stepwise protocol recapitulating developmental process. The induction rate of PDX1+NKX6.1+ cells was correlated with cell density in adherent cultures, and markedly improved with cell aggregation cultures. The positive effects of cell aggregation cultures on the differentiation of pancreatic bud cells were reproduced in multiple hESC/iPSC lines. The human PDX1+NKX6.1+ cells developed into pancreatic epithelia after implantation into immunocompromised mice. Moreover, human C-peptide secretion into mouse bloodstream was stimulated by glucose challenges after in vivo maturation. Taken together, these results suggest that cultures with high cell density are crucial for the differentiation of pancreas-committed progenitor cells from hESCs/iPSCs. Our findings may be applicable for the development of hESC/iPSC-based cell therapy for diabetes.

  14. Toxicity and outcome results of RTOG 9311: A phase I-II dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma

    International Nuclear Information System (INIS)

    Purpose: To evaluate prospectively the acute and late morbidities from a multiinstitutional three-dimensional radiotherapy dose-escalation study for inoperable non-small-cell lung cancer. Methods and materials: A total of 179 patients were enrolled in a Phase I-II three-dimensional radiotherapy dose-escalation trial. Of the 179 patients, 177 were eligible. The use of concurrent chemotherapy was not allowed. Twenty-five patients received neoadjuvant chemotherapy. Patients were stratified at escalating radiation dose levels depending on the percentage of the total lung volume that received >20 Gy with the treatment plan (V20). Patients with a V20 20 of 25-36% (Group 2) received doses of 70.9 Gy and 77.4 Gy, successively. The treatment arm for patients with a V20 ≥37% (Group 3) closed early secondary to poor accrual (2 patients) and the perception of excessive risk for the development of pneumonitis. Toxicities occurring or persisting beyond 90 days after the start of radiotherapy were scored as late toxicities. The estimated toxicity rates were calculated on the basis of the cumulative incidence method. Results: The following acute Grade 3 or worse toxicities were observed for Group 1: 70.9 Gy (1 case of weight loss), 77.4 Gy (nausea and hematologic toxicity in 1 case each), 83.8 Gy (1 case of hematologic toxicity), and 90.3 Gy (3 cases of lung toxicity). The following acute Grade 3 or worse toxicities were observed for Group 2: none at 70.9 Gy and 2 cases of lung toxicity at 77.4 Gy. No patients developed acute Grade 3 or worse esophageal toxicity. The estimated rate of Grade 3 or worse late lung toxicity at 18 months was 7%, 16%, 0%, and 13% for Group 1 patients receiving 70.9, 77.4, 83.8, or 90.3 Gy, respectively. Group 2 patients had an estimated late lung toxicity rate of 15% at 18 months for both 70.9 and 77.4 Gy. The prognostic factors for late pneumonitis in multivariate analysis were the mean lung dose and V20. The estimated rate of late Grade 3 or worse

  15. Zinc chlorophyll aggregates as hole transporters for biocompatible, natural-photosynthesis-inspired solar cells

    Science.gov (United States)

    Li, Yue; Sasaki, Shin-ichi; Tamiaki, Hitoshi; Liu, Cheng-Liang; Song, Jiaxing; Tian, Wenjing; Zheng, Enqiang; Wei, Yingjin; Chen, Gang; Fu, Xueqi; Wang, Xiao-Feng

    2015-11-01

    The intriguing properties of extremely efficient delocalization and migration of excitons in chlorophyll (Chl) J-type aggregates have inspired intense research activities toward their structural understanding, functional interpretation and mimicry synthesis. Herein, we demonstrated the J-aggregates of zinc methyl 3-devinyl-3-hydroxymethyl-pyropheophorbide a (ZnChl-1) generated by spin-coating method for the application as a hole transporter in titania-based solar cells using methyl trans-32-carboxypyropheophorbide a (H2Chl-2) or its zinc complex (ZnChl-2) as the sensitizer. The effective carrier mobility of the J-aggregates films was determined by the organic field-effect transistor to be 6.2 × 10-4 cm2 V-1 s-1. Solar cells sharing the architecture of FTO/H2Chl-2 or ZnChl-2 on TiO2/(ZnChl-1)n/Ag were fabricated and the factors that presumably determine their photovoltaic performances were discussed. The photovoltaic devices studied herein employing inexpensive and pollution-free biomaterials provide a unique solution of utilizing solar energy with a care of the important environmental issue.

  16. Quality of Life (QOL) Analysis of a Randomized Radiation Dose Escalation Non-Small Cell Lung Cancer (NSCLC) Study: Radiation Therapy Oncology Group (RTOG) Trial 0617

    Science.gov (United States)

    Movsas, Benjamin; Hu, Chen; Sloan, Jeffrey; Bradley, Jeffrey; Komaki, Ritsuko; Masters, Gregory; Kavadi, Vivek; Narayan, Samir; Michalski, Jeff; Johnson, Douglas W.; Koprowski, Christopher; Curran, Walter J.; Garces, Yolanda I.; Gaur, Rakesh; Wynn, Raymond B.; Schallenkamp, John; Gelblum, Daphna Y.; MacRae, Robert M; Paulus, Rebecca; Choy, Hak

    2015-01-01

    Importance A recent randomized radiation dose escalation trial in unresectable stage III NSCLC showed a lower survival in the high-dose arm (74Gy vs. 60Gy) with concurrent chemotherapy. Quality of life (QOL), an important secondary endpoint, is presented here. Objective The primary QOL hypothesis predicted a clinically meaningful decline (CMD) in QOL via the Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS) in the high-dose RT-arm at 3 months. Design RTOG 0617 was a randomized phase III study (conducted from Nov 2007 to Nov 2011) in stage III NSCLC using a 2×2 factorial design and stratified by histology, PET staging, performance status and radiation technique (3D-conformal RT [3DCRT] vs. intensity-modulated radiation [IMRT]). Setting 185 institutions in the USA and Canada. Participants Of 424 eligible stage III NSCLC patients randomized, 360 (85%) consented to QOL, of whom 313 (88%) completed baseline QOL assessments. Intervention for Clinical Trials 74Gy vs. 60Gy with concurrent and consolidation carboplatin/paclitaxel +/− cetuximab. Main Outcomes and Measures QOL was collected prospectively via FACT-Trial Outcome Index (FACT-TOI), equaling Physical-Well-Being (PWB) + Functional-Well-Being (FWB) + Lung Cancer Subscale (LCS). Data are presented at baseline & 3 and 12 months via minimal clinically meaningful changes of >=2 points for PWB, FWB or LCS or >=5 points for TOI. Results Patient demographics and baseline QOL scores were comparable between the 74Gy and 60Gy arms. Two-hundred-nineteen (72%) of living patients who completed QOL at baseline did so at 3 months and 137 (57%) of living patients did so at 12 months. Significantly more patients on 74Gy arm had clinically meaningful decline in FACT-LCS at 3 months than on the 60Gy arm (45% vs. 30%, p=0.02). At 12 months, fewer patients who received IMRT (vs 3DCRT) had clinically meaningful decline in FACT-LCS (21% vs 46%, p=0.003). Baseline FACT-TOI was associated with overall survival in

  17. Trade Study on Aggregation of Multiple 10-KW Solid Ozide Fuel Cell Power Modules

    Energy Technology Data Exchange (ETDEWEB)

    Ozpineci, B.

    2004-12-03

    According to the Solid State Energy Conversion Alliance (SECA) program guidelines, solid oxide fuel cells (SOFC) will be produced in the form of 3-10 kW modules for residential use. In addition to residential use, these modules can also be used in apartment buildings, hospitals, etc., where a higher power rating would be required. For example, a hospital might require a 250 kW power generating capacity. To provide this power using the SECA SOFC modules, 25 of the 10 kW modules would be required. These modules can be aggregated in different architectures to yield the necessary power. This report will show different approaches for aggregating numerous SOFC modules and will evaluate and compare each one with respect to cost, control complexity, ease of modularity, and fault tolerance.

  18. Silicification-induced cell aggregation for the sustainable production of H2 under aerobic conditions.

    Science.gov (United States)

    Xiong, Wei; Zhao, Xiaohong; Zhu, Genxing; Shao, Changyu; Li, Yaling; Ma, Weimin; Xu, Xurong; Tang, Ruikang

    2015-10-01

    Photobiological hydrogen production is of great importance because of its promise for generating clean renewable energy. In nature, green algae cannot produce hydrogen as a result of the extreme sensitivity of hydrogenase to oxygen. However, we find that silicification-induced green algae aggregates can achieve sustainable photobiological hydrogen production even under natural aerobic conditions. The core-shell structure of the green algae aggregates creates a balance between photosynthetic electron generation and hydrogenase activity, thus allowing the production of hydrogen. This finding provides a viable pathway for the solar-driven splitting of water into hydrogen and oxygen to develop green energy alternatives by using rationally designed cell-material complexes. PMID:26302695

  19. Simultaneous estimation of attenuation and structure parameters of aggregated red blood cells from backscatter measurements

    CERN Document Server

    Franceschini, Emilie; Cloutier, Guy

    2008-01-01

    The analysis of the ultrasonic frequency-dependent backscatter coefficient of aggregating red blood cells reveals information about blood structural properties. The difficulty to apply this technique in vivo is due to the frequency-dependent attenuation caused by intervening tissue layers that distorts the spectral content of backscattering properties from blood microstructures. An optimization method is proposed to simultaneously estimate tissue attenuation and blood structure factor. In an in vitro experiment, the method gave satisfactory estimates with relative errors below 22% for attenuations between 0.101 and 0.317 dB/cm/MHz, signal-to-noise ratios>28 dB and kR<2.7 (k being the wave number and R the aggregate radius).

  20. Entamoeba Clone-Recognition Experiments: Morphometrics, Aggregative Behavior, and Cell-Signaling Characterization.

    Science.gov (United States)

    Espinosa, Avelina; Paz-Y-Miño-C, Guillermo; Hackey, Meagan; Rutherford, Scott

    2016-05-01

    Studies on clone- and kin-discrimination in protists have proliferated during the past decade. We report clone-recognition experiments in seven Entamoeba lineages (E. invadens IP-1, E. invadens VK-1:NS, E. terrapinae, E. moshkovskii Laredo, E. moshkovskii Snake, E. histolytica HM-1:IMSS and E. dispar). First, we characterized morphometrically each clone (length, width, and cell-surface area) and documented how they differed statistically from one another (as per single-variable or canonical-discriminant analyses). Second, we demonstrated that amebas themselves could discriminate self (clone) from different (themselves vs. other clones). In mix-cell-line cultures between closely-related (E. invadens IP-1 vs. E. invadens VK-1:NS) or distant-phylogenetic clones (E. terrapinae vs. E. moshkovskii Laredo), amebas consistently aggregated with same-clone members. Third, we identified six putative cell-signals secreted by the amebas (RasGap/Ankyrin, coronin-WD40, actin, protein kinases, heat shock 70, and ubiquitin) and which known functions in Entamoeba spp. included: cell proliferation, cell adhesion, cell movement, and stress-induced encystation. To our knowledge, this is the first multi-clone characterization of Entamoeba spp. morphometrics, aggregative behavior, and cell-signaling secretion in the context of clone-recognition. Protists allow us to study cell-cell recognition from ecological and evolutionary perspectives. Modern protistan lineages can be central to studies about the origins and evolution of multicellularity. PMID:26990199

  1. Viscoelastic properties of whole blood. Influence of fast sedimenting red blood cell aggregates.

    Science.gov (United States)

    Schneditz, D; Rainer, F; Kenner, T

    1987-01-01

    Red blood cell (RBC) aggregation is known to be of deciding influence on erythrocyte sedimentation-rate (ESR) and on whole blood viscoelastic properties. The rheological behaviour of blood collected from a control-group with normal ESR is compared to the viscoelastic behaviour of blood collected from two groups with high to very high ESR, whose individuals are suffering from chronical polyarthritis and Morbus Bechterew, respectively. The rheological properties are evaluated by means of an oscillating-flow capillary-rheometer where the viscous (eta') and elastic (eta") component of the complex viscosity (eta) is measured at a constant frequency of 2 Hz. Correcting for the varying hematocrit of the different blood samples according to an exponential equation, the viscoelastic data are found to be elevated in the groups with high ESR. For the viscous properties this is only due to the increase of the plasma viscosity. A correction for the plasma viscosity, however, shows that the viscous properties at low shear- rates (2s-1) are significantly reduced, whereas elastic properties in a range of medium shear-rates (10s-1 to 50s-1) are significantly increased (P less than 0.001, t-test of Student). This result is discussed to be due to the high packing density of the RBC in fast sedimenting aggregates. High packing density reduces the effective volume of the RBC but increases the stiffness of the aggregates. PMID:3651579

  2. Understanding the escalation of Syrian Conflict

    OpenAIRE

    Ghimire, Manju

    2014-01-01

    The main purpose of this project is to investigate the escalation of the conflict in Syria, which emerges since 2011.At first it was a peaceful protest against the Assad regime- asking for the reformation gradually the protest turned into a bloody civil war within a year. To get into the understanding regarding the escalation of the conflict and the situation in Syria, I have tried to observe the impacts of external and internal factors and their role in the escalation of the conflict.

  3. Fibronectin-like protein in Porifera: its role in cell aggregation.

    Science.gov (United States)

    Labat-Robert, J; Robert, L; Auger, C; Lethias, C; Garrone, R

    1981-01-01

    Experiments were carried out on a freshwater sponge (Ephydatia mulleri) in order to demonstrate the presence of fibronectin in Porifera. By using antibodies to highly purified human plasma fibronectin, the presence of a similar or identical protein could be demonstrated in the membranes of E. mulleri cells such as epithelial cells, fibroblast-like cells, and choanocytes. The reaction was specific, could be abolished by the addition of excess fibronectin, and was not observed with nonimmune rabbit serum. The immune fluorescent reaction became stronger when the sponge cells were pretreated with acetone and could also be observed, although with a less intense staining, on the intercellular matrix. This shows the predominant presence of a sponge fibronectin-like protein in the cell membranes and also its presence to a lesser extent in the intercellular matrix. When dissociated sponge cells were led to reassociate under the microscope, reassociation could be completely inhibited by anti-human fibronectin antiserum up to a dilution of 1:120 and partially inhibited up to a dilution of 1:240. The reassociation of dissociated sponge cells could also be inhibited by the addition of purified gelatin but not with serum albumin or with a normal, nonimmune rabbit serum. These results clearly indicate that a sponge cell fibronectin-like protein may play an important role as the (or one of the) recognition site(s) of the aggregation factor(s) and can therefore be directly involved in cell association, morphogenesis, and differentiation. Images PMID:7031644

  4. Organic nanoparticles with aggregation-induced emission for tracking bone marrow stromal cells in the rat ischemic stroke model.

    Science.gov (United States)

    Li, Kai; Yamamoto, Mie; Chan, Su Jing; Chiam, Mun Yee; Qin, Wei; Wong, Peter Tsun Hon; Yim, Evelyn King Fai; Tang, Ben Zhong; Liu, Bin

    2014-12-14

    Organic nanoparticles (NPs) with aggregation-induced emission (AIE) have been successfully used for tracking bone marrow stromal cells (BMSCs) in rats with ischemic stroke, highlighting the great potential of such fluorescent NPs in understanding the fate of transplanted stem cells for cell-based therapies. PMID:25267167

  5. Two cell surface proteins bind the sponge Microciona prolifera aggregation factor.

    Science.gov (United States)

    Varner, J A; Burger, M M; Kaufman, J F

    1988-06-15

    Two extracellular matrix cell surface proteins which bind the proteoglycan-like aggregation factor from the marine sponge Microciona prolifera (MAF) and which may function as physiological receptors for MAF were identified and characterized for the first time. By probing nitrocellulose blots of nonreducing sodium dodecyl sulfate gels containing whole sponge cell protein with iodinated MAF, a 210- and a 68-kDa protein, which have native molecular masses of approximately 200-400 and 70 kDa, were identified. MAF binding to blots is species-specific. It is also sensitive to reduction and is completely abolished by pretreatment of live cells with proteases, as was cellular aggregation, indicating that the 210- and 68-kDa proteins may be located on the cell surface. The additional observations that the 68 kDa is an endoglycosidase F-sensitive glycoprotein and that antisera against whole sponge cells or membranes can immunoprecipitate the 210 kDa when prebound to intact cells are consistent with a cell surface location. Both proteins can be isolated from sponge cell membranes and from the sponge skeleton (insoluble extracellular matrix), but the 210-kDa MAF-binding protein can also be found in the soluble extracellular matrix (buffer washes of cells and skeleton) as well. A third MAF-binding protein of molecular mass 95 kDa was also found in the sponge extracellular matrix but rarely on cells. Both of the cell-associated 210- and 68-kDa proteins are nonintegral membrane proteins, based on Triton X-114 phase separation, flotation of liposomes containing sponge membrane lysates, and their extraction from membranes by buffer washes. Both proteins bind MAF affinity resins, indicating that they each exhibit a moderate affinity for MAF under native conditions. They can also be separated from each other and from the bulk of the protein in an octylpolyoxyethylene extract of membranes by fast protein liquid chromatography Mono Q anion exchange chromatography, as assessed by native

  6. Enhanced charge transport properties by strengthened necks between TiO2 aggregates for dye sensitized solar cells

    International Nuclear Information System (INIS)

    The electron diffusion in the TiO2 aggregate network was enhanced through the addition of TiO2 nanoparticles with preferential filling at the necks between adjacent TiO2 aggregates, which resulted in strengthening the connections, while retaining the porous structure of the TiO2 network. The fortified necks was found to reduce the transport resistance (Rt) by allowing facile transfer of electrons from one aggregate to another, while the scattering effect of the TiO2 aggregate network got weakened with adding the TiO2 nanoparticles as a result of reduction of the light scattering centers such as the necks and gaps between the aggregates. However, due to the increase in surface area as the TiO2 nanoparticles were added, the diminished light scattering effect of the aggregate network was compensated and even the highest performance was achieved when the 10% TiO2 nanoparticle was added into the TiO2 aggregate film, suggesting that widening necks between sub-micrometer sized light scatters such as an aggregate would be a good strategy in achieving further improvement of power conversion efficiency of dye sensitized solar cells through the improved charge transport property. - Highlights: • The added nanoparticles fill the necks preferentially. • The fortified necks made electron transport in the TiO2 network facilitated. • Balancing between light scattering and dye uptake should be considered

  7. The study of MCF-7 cell aggregates encapsulated in alginate microbeads under the modeled weightlessness

    Science.gov (United States)

    Li, Yu; Zheng, Hongxia; Tian, Weiming; Yu, Lei; Zhang, Yao; Han, Fengtong

    Assessing the risks associated with exposure to the microgravity encountered in space is essential for the success of long-term space exploration. For understanding of the effects of microgravity, either traditional 2-dimensional (2D) cell cultures of adherent cell populations or animal models were typically used. The 2D in vitro systems do not allow assessment of the dynamic effects of intercellular interactions within tissues, whereas potentially confounding factors tend to be overlooked in animal models. Therefore novel cell culture model representative of the cellular interactions and with extracellular matrix present in tissues needs to be used. Toward this overall goal, 3D cell aggregates of breast cancer cell line MCF-7 was constructed by encapsu-lating in alginate microbeads. With this model we studied the simulated microgravity effects on MCF-7 by incubating the microbeads in NASA rotary cell culture system with a rate of 15rpm.We found MCF-7 showed higher proliferation rate than that of control group character-ized by up regulation of Ki-67. Further study showed that the effect was achieved by activating the MAPK intercellular signaling pathway. The result is inconsistent with previous conclusion obtained with 2D cell culture model which indicated that 3D cell culture model maybe better for elucidating the microgravity effects.

  8. Biogrid--a microfluidic device for large-scale enzyme-free dissociation of stem cell aggregates.

    Science.gov (United States)

    Wallman, Lars; Åkesson, Elisabet; Ceric, Dario; Andersson, Per Henrik; Day, Kelly; Hovatta, Outi; Falci, Scott; Laurell, Thomas; Sundström, Erik

    2011-10-01

    Culturing stem cells as free-floating aggregates in suspension facilitates large-scale production of cells in closed systems, for clinical use. To comply with GMP standards, the use of substances such as proteolytic enzymes should be avoided. Instead of enzymatic dissociation, the growing cell aggregates may be mechanically cut at passage, but available methods are not compatible with large-scale cell production and hence translation into the clinic becomes a severe bottle-neck. We have developed the Biogrid device, which consists of an array of micrometerscale knife edges, micro-fabricated in silicon, and a manifold in which the microgrid is placed across the central fluid channel. By connecting one side of the Biogrid to a syringe or a pump and the other side to the cell culture, the culture medium with suspended cell aggregates can be aspirated, forcing the aggregates through the microgrid, and ejected back to the cell culture container. Large aggregates are thereby dissociated into smaller fragments while small aggregates pass through the microgrid unaffected. As proof-of-concept, we demonstrate that the Biogrid device can be successfully used for repeated passage of human neural stem/progenitor cells cultured as so-called neurospheres, as well as for passage of suspension cultures of human embryonic stem cells. We also show that human neural stem/progenitor cells tolerate transient pressure changes far exceeding those that will occur in a fluidic system incorporating the Biogrid microgrids. Thus, by using the Biogrid device it is possible to mechanically passage large quantities of cells in suspension cultures in closed fluidic systems, without the use of proteolytic enzymes. PMID:21850297

  9. Development of a valve-based cell printer for the formation of human embryonic stem cell spheroid aggregates

    International Nuclear Information System (INIS)

    In recent years, the use of a simple inkjet technology for cell printing has triggered tremendous interest and established the field of biofabrication. A key challenge has been the development of printing processes which are both controllable and less harmful, in order to preserve cell and tissue viability and functions. Here, we report on the development of a valve-based cell printer that has been validated to print highly viable cells in programmable patterns from two different bio-inks with independent control of the volume of each droplet (with a lower limit of 2 nL or fewer than five cells per droplet). Human ESCs were used to make spheroids by overprinting two opposing gradients of bio-ink; one of hESCs in medium and the other of medium alone. The resulting array of uniform sized droplets with a gradient of cell concentrations was inverted to allow cells to aggregate and form spheroids via gravity. The resulting aggregates have controllable and repeatable sizes, and consequently they can be made to order for specific applications. Spheroids with between 5 and 140 dissociated cells resulted in spheroids of 0.25–0.6 mm diameter. This work demonstrates that the valve-based printing process is gentle enough to maintain stem cell viability, accurate enough to produce spheroids of uniform size, and that printed cells maintain their pluripotency. This study includes the first analysis of the response of human embryonic stem cells to the printing process using this valve-based printing setup. (paper)

  10. Inhibition of Rho-Associated Protein Kinase Increases the Angiogenic Potential of Mesenchymal Stem Cell Aggregates via Paracrine Effects.

    Science.gov (United States)

    Hong, Soyoung; Lee, Jae Yeon; Hwang, Changmo; Shin, Jennifer H; Park, Yongdoo

    2016-02-01

    The aggregation of multiple cells, such as mesenchymal condensation, is an important biological process in skeletal muscle development, osteogenesis, and adipogenesis. Due to limited in vivo study model systems, a simple and effective in vitro three-dimensional (3D) aggregation system is required to study the mechanisms of multicellular aggregation and its applications. We first generated controlled mesenchymal stem cell (MSC) aggregates using a bioprinting technique to monitor their aggregation and sprouting. We induced the angiogenic potential of the MSCs through chemical inhibition of the Rho/Rho-associated protein kinase (ROCK) pathway, which led to hairy sprouting in the aggregates. The angiogenic potential of this 3D construct was then tested by subcutaneously implanting the Matrigel with 3D MSC aggregates in a rat. Treatment of 3D MSCs with the ROCK inhibitor, Y27632, increased their angiogenic activity in vivo. The gene expressions and histological staining indicated that angiogenesis and neovascularization were mainly regulated by the paracrine factors secreted from human 3D MSC constructs. Our results demonstrate the enhancement of the angiogenic potential of the MSC constructs through the secretion of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) by the inhibition of the Rho/ROCK pathway. PMID:26592750

  11. Electrophoretic and aggregation behavior of bovine, horse and human red blood cells in plasma and in polymer solutions.

    Science.gov (United States)

    Bäumler, H; Neu, B; Mitlöhner, R; Georgieva, R; Meiselman, H J; Kiesewetter, H

    2001-01-01

    The electrophoretic mobility of native and glutaraldehyde-fixed bovine, human, and horse red blood cells (RBC) was investigated as a function of ionic strength (5-150 mM) and concentration of 464 kDa dextran (2 and 3 g/dl); RBC aggregation in autologous plasma and in dextran solutions was also measured. In agreement with previous observations, human and horse RBC form stable rouleaux whereas bovine RBC do not aggregate in either plasma or in dextran 464 kDa solutions. Electrophoretic measurements showed a species-dependent adsorption and depletion of dextran that can be theoretically evaluated. Adsorption of polymer is not a prerequisite for RBC aggregation (bovine RBC show the highest amount of adsorbed dextran yet do not aggregate). Aggregate formation thus occurs as long as the Gibbs free energy difference, given by the osmotic pressure difference between the bulk phase and the polymer-depleted region between two RBC, is larger than the steric and electrostatic repulsive energy contributed by the macromolecules present on the RBC surface. With increasing bulk-phase polymer concentration the depletion layer thickness decreases and the amount of adsorbed macromolecules increases, thereby resulting in an increase of the repulsive component of the interaction energy and decreased aggregation. We thus view electrophoretic measurements of RBC in various media as an important tool for understanding polymer behavior near the red cell surface and hence the mechanisms involved in RBC aggregation. PMID:11381164

  12. Power asymmetry and escalation in bargaining

    OpenAIRE

    Vollstädt, Ulrike

    2011-01-01

    Bargaining is prevalent in economic interactions. Under complete information, game theory predicts efficient bargaining outcomes (immediate acceptance of first offer) (see Rubinstein, 1982). However, continuous rejections of offers leading to inefficient delays (escalation) have regularly been found in previous bargaining experiments even under complete information (see Roth, 1995). I test experimentally (1) whether power asymmetry leads to more escalation in bargaining and (2) whether perspe...

  13. Concurrent chemoradiotherapy with tomotherapy in locally advanced non-small cell lung cancer: a phase i, docetaxel dose-escalation study, with hypofractionated radiation regimen

    OpenAIRE

    Bearz, Alessandra; Minatel, Emilio; Rumeileh, Imad Abu; Borsatti, Eugenio; Talamini, Renato; Franchin, Giovanni; Gobitti, Carlo; Del Conte, Alessandro; Trovò, Marco; Baresic, Tanja

    2013-01-01

    Background Concurrent chemo-radiotherapy is demonstrately superior to sequential chemo-radiotherapy in the treatment of advanced Non-Small-Cell Lung Cancer not suitable for surgery. Docetaxel is considered to enhance the cytotoxic effect of radiotherapy on the tumour cells. Tomotherapy (HT) is a novel radiotherapeutic technique, which allows the delivery of Image Guided-IMRT (IG-IMRT), with a highly conformal radiation dose distribution. The goal of the study was to estimate tolerability of D...

  14. Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures

    International Nuclear Information System (INIS)

    Despite the widespread use of Cannabis as recreational drug or as medicine, little is known about its toxicity. The accumulation, metabolism and toxicity of THC were analyzed 10 days after a single treatment, and after repeated exposures during 10 days. Mixed-cell aggregate cultures of fetal rat telencephalon were used as in vitro model, as well as aggregates enriched either in neurons or in glial cells. It was found that THC accumulated preferentially in neurons, and that glia-neuron interactions decreased THC accumulation. The quantification of 11-OH-THC and of THC-COOH showed that brain aggregates were capable of THC metabolism. No cell-type difference was found for the metabolite 11-OH-THC, whereas the THC-COOH content was higher in mixed-cell cultures. No cell death was found at THC concentrations of 2 μM in single treatment and of 1 μM and 2 μM in repeated treatments. Neurons, and particularly GABAergic neurons, were most sensitive to THC. Only the GABAergic marker was affected after the single treatment, whereas the GABAergic, cholinergic and astrocytic markers were decreased after the repeated treatments. JWH 015, a CB2 receptor agonist, showed effects similar to THC, whereas ACEA, a CB1 receptor agonist, had no effect. The expression of the cytokine IL-6 was upregulated 48 h after the single treatment with 5 μM of THC or JWH 015, whereas the expression of TNF-α remained unchanged. These results suggest that the adverse effects of THC were related either to THC accumulation or to cannabinoid receptor activation and associated with IL-6 upregulation

  15. Conductometric study of shear-dependent processes in red cell suspensions. I. Effect of red blood cell aggregate morphology on blood conductance.

    Science.gov (United States)

    Pribush, A; Meyerstein, D; Meyerstein, N

    2004-01-01

    The conductance and capacitance of flowing and quiescent red blood cell (RBC) suspensions were measured at a frequency of 0.2 MHz. The results demonstrate that the time-dependent changes in the conductance recorded during the aggregation process differ in nature for suspensions of short linear rouleaux, branched aggregates and RBC networks. It is shown that the conductance of RBC suspensions measured during the aggregation and disaggregation processes follows the morphological transformations of the RBC aggregates. Thus, this method enables characterization of the morphology of RBC aggregates formed in whole blood and in suspensions with physiological hematocrits both under flow conditions and in stasis. These results in combination with previous ones suggest that this technique can be used for studies of dynamic RBC aggregation and probably for diagnostic use. PMID:14967887

  16. Production Pattern of Ajmalicine in Catharanthus roseus (L. G. Don. Cell Aggregates Culture in the Airlift Bioreactor

    Directory of Open Access Journals (Sweden)

    RIZKITA RACHMI ESYANTI

    2006-12-01

    Full Text Available A research has been conducted to optimize the rate of aeration and initial weight of cell aggregates in the production of ajmalicine in Catharanthus roseus cell culture in airlift bioreactor. Catharanthus roseus culture were grown in Zenk medium with the addition of 2.50 x 10-6 M naphthalene acetic acid (NAA and 10-5 M benzyl amino purine (BAP. Cell aggregates were sub-cultured two times before transferring 20 and 30 g/fw of cell aggregates into bioreactor, respectively, and aerated with the rate of 0.25 l min-1 and 0.34 l min-1, respectively. The pattern of ajmalicine production in bioreactor were observed in every three days within 24 days. Qualitative and quantitative analysis were conducted using HPLC connected to Cromatopac CL-7A Plus. The results showed that the cell aggregates and medium contain ajmalicine. The highest concentration was obtained in combination of 30 g/fw and 0.34 l min-1 aeration compare to 20 g/fw - 0.25 l min-1, 20 g/fw - 0.34 l min-1, as well as 30 g/fw – 0.25 l min-1. The highest ajmalicine content in cell aggregates was obtained on the 12 days (79.23 µg g-1 whilst in medium was obtained in the 18th days (981.15 µg l-1.

  17. The Effect of Pulsatile Versus Nonpulsatile Blood Flow on Viscoelasticity and Red Blood Cell Aggregation in Extracorporeal Circulation

    OpenAIRE

    Ahn, Chi Bum; Kang, Yang Jun; Kim, Myoung Gon; Yang, Sung; Lim, Choon Hak; Son, Ho Sung; Kim, Ji Sung; Lee, So Young; Son, Kuk Hui; Sun, Kyung

    2016-01-01

    Background Extracorporeal circulation (ECC) can induce alterations in blood viscoelasticity and cause red blood cell (RBC) aggregation. In this study, the authors evaluated the effects of pump flow pulsatility on blood viscoelasticity and RBC aggregation. Methods Mongrel dogs were randomly assigned to two groups: a nonpulsatile pump group (n=6) or a pulsatile pump group (n=6). After ECC was started at a pump flow rate of 80 mL/kg/min, cardiac fibrillation was induced. Blood sampling was perfo...

  18. Islet-like cell aggregates generated from human adipose tissue derived stem cells ameliorate experimental diabetes in mice.

    Directory of Open Access Journals (Sweden)

    Vikash Chandra

    Full Text Available BACKGROUND: Type 1 Diabetes Mellitus is caused by auto immune destruction of insulin producing beta cells in the pancreas. Currently available treatments include transplantation of isolated islets from donor pancreas to the patient. However, this method is limited by inadequate means of immuno-suppression to prevent islet rejection and importantly, limited supply of islets for transplantation. Autologous adult stem cells are now considered for cell replacement therapy in diabetes as it has the potential to generate neo-islets which are genetically part of the treated individual. Adopting methods of islet encapsulation in immuno-isolatory devices would eliminate the need for immuno-suppressants. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we explore the potential of human adipose tissue derived adult stem cells (h-ASCs to differentiate into functional islet like cell aggregates (ICAs. Our stage specific differentiation protocol permit the conversion of mesodermic h-ASCs to definitive endoderm (Hnf3β, TCF2 and Sox17 and to PDX1, Ngn3, NeuroD, Pax4 positive pancreatic endoderm which further matures in vitro to secrete insulin. These ICAs are shown to produce human C-peptide in a glucose dependent manner exhibiting in-vitro functionality. Transplantation of mature ICAs, packed in immuno-isolatory biocompatible capsules to STZ induced diabetic mice restored near normoglycemia within 3-4 weeks. The detection of human C-peptide, 1155±165 pM in blood serum of experimental mice demonstrate the efficacy of our differentiation approach. CONCLUSIONS: h-ASC is an ideal population of personal stem cells for cell replacement therapy, given that they are abundant, easily available and autologous in origin. Our findings present evidence that h-ASCs could be induced to differentiate into physiologically competent functional islet like cell aggregates, which may provide as a source of alternative islets for cell replacement therapy in type 1 diabetes.

  19. Antigen 43 from Escherichia coli induces inter- and intraspecies cell aggregation and changes in colony morphology of Pseudomonas fluorescens

    DEFF Research Database (Denmark)

    Kjærgaard, Kristian; Schembri, Mark; Hasman, Henrik;

    2000-01-01

    distinct frizzy colony morphology in E. coli. Here we show that Ag43 can be expressed in a functional form on the surface of the environmentally important Pseudomonas fluorescens strain SBW25 with ensuing cell aggregation and frizzy colony types. Using green fluorescence protein-tagged cells, we...... demonstrate that Ag43 can be used as a tool to provide interspecies cell aggregation between E. coli and P. fluorescens. Furthermore, Ag43 expression enhances biofilm formation in P. fluorescens to glass surfaces. The versatility of this protein was also reflected in Ag43 surface display in a variety of other...

  20. Alginate Encapsulation Parameters Influence the Differentiation of Microencapsulated Embryonic Stem Cell Aggregates

    Science.gov (United States)

    Wilson, Jenna L.; Najia, Mohamad Ali; Saeed, Rabbia; McDevitt, Todd C.

    2014-01-01

    Pluripotent embryonic stem cells (ESCs) have tremendous potential as tools for regenerative medicine and drug discovery, yet the lack of processes to manufacture viable and homogenous cell populations of sufficient numbers limits the clinical translation of current and future cell therapies. Microencapsulation of ESCs within microbeads can shield cells from hydrodynamic shear forces found in bioreactor environments while allowing for sufficient diffusion of nutrients and oxygen through the encapsulation material. Despite initial studies examining alginate microbeads as a platform for stem cell expansion and directed differentiation, the impact of alginate encapsulation parameters on stem cell phenotype has not been thoroughly investigated. Therefore, the objective of this study was to systematically examine the effects of varying alginate compositions on microencapsulated ESC expansion and phenotype. Pre-formed aggregates of murine ESCs were encapsulated in alginate microbeads composed of a high or low ratio of guluronic to mannuronic acid residues (High G and High M, respectively), with and without a poly-l-lysine (PLL) coating, thereby providing four distinct alginate bead compositions for analysis. Encapsulation in all alginate compositions was found to delay differentiation, with encapsulation within High G alginate yielding the least differentiated cell population. The addition of a PLL coating to the High G alginate prevented cell escape from beads for up to 14 days. Furthermore, encapsulation within High M alginate promoted differentiation toward a primitive endoderm phenotype. Taken together, the findings of this study suggest that distinct ESC expansion capacities and differentiation trajectories emerge depending on the alginate composition employed, indicating that encapsulation material physical properties can be used to control stem cell fate. PMID:24166004

  1. Aggregative adherent strains of Corynebacterium pseudodiphtheriticum enter and survive within HEp-2 epithelial cells

    Directory of Open Access Journals (Sweden)

    Monica Cristina de Souza

    2012-06-01

    Full Text Available Corynebacterium pseudodiphtheriticum is a well-known human pathogen that mainly causes respiratory disease and is associated with high mortality in compromised hosts. Little is known about the virulence factors and pathogenesis of C. pseudodiphtheriticum. In this study, cultured human epithelial (HEp-2 cells were used to analyse the adherence pattern, internalisation and intracellular survival of the ATCC 10700 type strain and two additional clinical isolates. These microorganisms exhibited an aggregative adherence-like pattern to HEp-2 cells characterised by clumps of bacteria with a "stacked-brick" appearance. The differences in the ability of these microorganisms to invade and survive within HEp-2 cells and replicate in the extracellular environment up to 24 h post infection were evaluated. The fluorescent actin staining test demonstrated that actin polymerisation is involved in the internalisation of the C. pseudodiphtheriticum strains. The depolymerisation of microfilaments by cytochalasin E significantly reduced the internalisation of C. pseudodiphtheriticum by HEp-2 cells. Bacterial internalisation and cytoskeletal rearrangement seemed to be partially triggered by the activation of tyrosine kinase activity. Although C. pseudodiphtheriticum strains did not demonstrate an ability to replicate intracellularly, HEp-2 cells were unable to fully clear the pathogen within 24 h. These characteristics may explain how some C. pseudodiphtheriticum strains cause severe infection in human patients.

  2. A Microwell Cell Culture Platform for the Aggregation of Pancreatic β-Cells

    OpenAIRE

    Bernard, Abigail B.; Lin, Chien-Chi; Anseth, Kristi S.

    2012-01-01

    Cell–cell contact between pancreatic β-cells is important for maintaining survival and normal insulin secretion. Various techniques have been developed to promote cell–cell contact between β-cells, but a simple yet robust method that affords precise control over three-dimensional (3D) β-cell cluster size has not been demonstrated. To address this need, we developed a poly(ethylene glycol) (PEG) hydrogel microwell platform using photolithography. This microwell cell-culture platform promotes t...

  3. The effect of red blood cell aggregation on velocity and cell-depleted layer characteristics of blood in a bifurcating microchannel

    OpenAIRE

    Sherwood, J. M.; Dusting, J.; Kaliviotis, E; Balabani, S.

    2012-01-01

    Red blood cell (RBC) aggregation is a multifaceted phenomenon, and whether it is generally beneficial or deleterious remains unclear. In order to better understand its effect on microvascular blood flow, the phenomenon must be studied in complex geometries, as it is strongly dependent on time, flow, and geometry. The cell-depleted layer (CDL) which forms at the walls of microvessels has been observed to be enhanced by aggregation; however, details of the characteristics of the CDL in complex ...

  4. TIAF1 self-aggregation in peritumor capsule formation, spontaneous activation of SMAD-responsive promoter in p53-deficient environment, and cell death

    OpenAIRE

    Chang, J-Y; Chiang, M-F; Lin, S-R; Lee, M-H; H. He; Chou, P-Y; Chen, S-J; Chen, Y-A; Yang, L-Y; Lai, F-J; Hsieh, C-C; Hsieh, T-H; Sheu, H-M; Sze, C-I; Chang, N-S

    2012-01-01

    Self-aggregation of transforming growth factor β (TGF-β)1-induced antiapoptotic factor (TIAF1) is known in the nondemented human hippocampus, and the aggregating process may lead to generation of amyloid β (Aβ) for causing neurodegeneration. Here, we determined that overexpressed TIAF1 exhibits as aggregates together with Smad4 and Aβ in the cancer stroma and peritumor capsules of solid tumors. Also, TIAF1/Aβ aggregates are shown on the interface between brain neural cells and the metastatic ...

  5. Aqueous Extract of Paeonia lactiflora and Paeoniflorin as Aggregation Reducers Targeting Chaperones in Cell Models of Spinocerebellar Ataxia 3

    Directory of Open Access Journals (Sweden)

    Kuo-Hsuan Chang

    2013-01-01

    Full Text Available Spinocerebellar ataxia (SCA types 1, 2, 3, 6, 7, and 17 as well as Huntington’s disease are a group of neurodegenerative disorders caused by expanded CAG repeats encoding a long polyglutamine (polyQ tract in the respective proteins. Evidence has shown that the accumulation of intranuclear and cytoplasmic misfolded polyQ proteins leads to apoptosis and cell death. Thus suppression of aggregate formation is expected to inhibit a wide range of downstream pathogenic events in polyQ diseases. In this study, we established a high-throughput aggregation screening system using 293 ATXN3/Q75-GFP cells and applied this system to test the aqueous extract of Paeonia lactiflora (P. lactiflora and its constituents. We found that the aggregation can be significantly prohibited by P. lactiflora and its active compound paeoniflorin. Meanwhile, P. lactiflora and paeoniflorin upregulated HSF1 and HSP70 chaperones in the same cell models. Both of them further reduced the aggregation in neuronal differentiated SH-SY5Y ATXN3/Q75-GFP cells. Our results demonstrate how P. lactiflora and paeoniflorin are likely to work on polyQ-aggregation reduction and provide insight into the possible working mechanism of P. lactiflora in SCA3. We anticipate our paper to be a starting point for screening more potential herbs for the treatment of SCA3 and other polyQ diseases.

  6. Aggregation behavior of red blood cells in shear flow. A theoretical interpretation of simultaneous rheo-optical and viscometric measurements.

    Science.gov (United States)

    Berli, C L; Quemada, D

    2001-01-01

    A theoretical interpretation of simultaneous viscosity measurements and light backscattering experiments is carried out in the framework of the structural model for concentrated dispersions proposed previously by one of the authors. The work is mainly focused on erythrocyte aggregation, hence spherical as well as linear aggregates (rouleaux) were considered in the modeling. A connection between the structural parameters provided by each technique is established, in particular the characteristic shear rates for break up of aggregates. Theoretical predictions were then applied to experimental data of human blood collected from patients with different diseases in a hospital data bank. Finally, we conclude that the structural modeling proposed permits a reasonably good correlation between experimental data of viscometry and light backscattering from blood samples, leading to new perspectives in the analysis of the red blood cell aggregation phenomena. PMID:11381163

  7. A Phase I/II Radiation Dose Escalation Study With Concurrent Chemotherapy for Patients With Inoperable Stages I to III Non-Small-Cell Lung Cancer: Phase I Results of RTOG 0117

    International Nuclear Information System (INIS)

    Purpose: In preparation for a Phase III comparison of high-dose versus standard-dose radiation therapy, this Phase I/II study was initiated to establish the maximum tolerated dose of radiation therapy in the setting of concurrent chemotherapy, using three-dimensional conformal radiation therapy for non-small-cell lung cancer. Methods and Materials: Eligibility included patients with histologically proven, unresectable Stages I to III non-small-cell lung cancer. Concurrent chemotherapy consisted of paclitaxel, 50 mg/m2, and carboplatin, AUC of 2, given weekly. The radiation dose was to be sequentially intensified by increasing the daily fraction size, starting from 75.25 Gy/35 fractions. Results: The Phase I portion of this study accrued 17 patients from 10 institutions and was closed in January 2004. After the initial 8 patients were accrued to cohort 1, the trial closed temporarily on September 26, 2002, due to reported toxicity. Two acute treatment-related dose-limiting toxicities (DLTs) were reported at the time: a case of grade 5 and grade 3 radiation pneumonitis. The protocol, therefore, was revised to de-escalate the radiation therapy dose (74 Gy/37 fractions). Patients in cohort 1 continued to develop toxicity, with 6/8 (75%) patients eventually developing grade ≥3 events. Cohort 2 accrued 9 patients. There was one DLT, a grade 3 esophagitis, in cohort 2 in the first 5 patients (1/5 patients) and no DLTs for the next 2 patients (0/2 patients). Conclusions: The maximum tolerated dose was determined to be 74 Gy/37 fractions (2.0 Gy per fraction) using three-dimensional conformal radiation therapy with concurrent paclitaxel and carboplatin therapy. This dose level in the Phase II portion has been well tolerated, with low rates of acute and late lung toxicities.

  8. Experiment on ``discovery'' STS 51-C: Aggregation of red cells and thrombocytes in heart disease, hyperlipidaemia and other conditions

    Science.gov (United States)

    Dintenfass, L.

    The aim of this experiment was to study aggregation of red cells in the blood of patients with ischaemic heart disease, diabetes, hyperlipidaemia, and (silent) cancer, and in two normal donors. Reconstituted blood using IgG was also used. The instrument, the automated slit-capillary photo-viscometer (100 kg weight) was set on the middeck of the Space Shuttle. An analogous instrument was at the Kennedy Space Center. Blood was obtained from donors, anticoagulated, and adjusted to haematocrit of 30% using native plasma. Experiments took place at 25°C, during which blood was forced to flow in the slit formed by two parallel glass plates. Macro and microphotography was carried out at specific intervals controlled by a computer. During stasis, lasting 6 minutes, aggregates (or clumps) of the red cells were formed. Results indicated that red cell aggregates do form under zero-G; that such aggregates are smaller than the ones obtained at one-G; that morphology is different, the zero-G showing rouleaux while one-G showing usual sludge-like clumps of red cells in all severe disorders. Platelets appeared to remain monodisperse under zero-G. Assuming that these data can be confirmed, one could suggest that zero-G affects cell-cell interaction, and may consequently influence the internal microstructure of the cell membrane and of the receptors, as well as their activity. Gravitational studies may thus open a new door on immunology and haematology in general.

  9. The common inhaled anesthetic isoflurane increases aggregation of huntingtin and alters calcium homeostasis in a cell model of Huntington's disease

    International Nuclear Information System (INIS)

    Isoflurane is known to increase β-amyloid aggregation and neuronal damage. We hypothesized that isoflurane will have similar effects on the polyglutamine huntingtin protein and will cause alterations in intracellular calcium homeostasis. We tested this hypothesis in striatal cells from the expanded glutamine huntingtin knock-in mouse (STHdhQ111/Q111) and wild type (STHdhQ7/Q7) striatal neurons. The primary cultured neurons were exposed for 24 h to equipotent concentrations of isoflurane, sevoflurane, and desflurane in the presence or absence of extracellular calcium and with or without xestospongin C, a potent endoplasmic reticulum inositol 1,4,5-trisphosphate (InsP3) receptor antagonist. Aggregation of huntingtin protein, cell viability, and calcium concentrations were measured. Isoflurane, sevoflurane, and desflurane all increased the aggregation of huntingtin in STHdhQ111/Q111 cells, with isoflurane having the largest effect. Isoflurane induced greater calcium release from the ER and relatively more cell damage in the STHdhQ111/Q111 huntingtin cells than in the wild type STHdhQ7/Q7 striatal cells. However, sevoflurane and desflurane caused less calcium release from the ER and less cell damage. Xestospongin C inhibited the isoflurane-induced calcium release from the ER, aggregation of huntingtin, and cell damage in the STHdhQ111/Q111 cells. In summary, the Q111 form of huntingtin increases the vulnerability of striatal neurons to isoflurane neurotoxicity through combined actions on the ER IP3 receptors. Calcium release from the ER contributes to the anesthetic induced huntingtin aggregation in STHdhQ111/Q111 striatal cells.

  10. Structural insights into the multi-determinant aggregation of TDP-43 in motor neuron-like cells.

    Science.gov (United States)

    Bozzo, F; Salvatori, I; Iacovelli, F; Mirra, A; Rossi, S; Cozzolino, M; Falconi, M; Valle, C; Carrì, M T

    2016-10-01

    TDP-43 is aggregated in patients with ALS and FLTD through mechanisms still incompletely understood. Since aggregation in the cytosol is most probably responsible for the delocalization and loss of proper RNA-binding function of TDP-43 in the nucleus, interception of the formation of aggregates may represent a useful therapeutic option. In this study, we investigated the relative importance of the N-terminal and C-terminal moieties of TDP-43 in the aggregation process and the weight of each of the six cysteine residues in determining unfolding and aggregation of the different domains. We report that cytoplasmic inclusions formed by WT and mutant TDP-43 in motor neuron-like NSC34 cells are redox-sensitive only in part, and contain at least two components, i.e. oligomers and large aggregates, that are made of different molecular species. The two N-terminal cysteine residues contribute to the seeding for the first step in oligomerization, which is then accomplished by mechanisms depending on the four cysteines in the RNA-recognition motifs. Cysteine-independent large aggregates contain unfolded isoforms of the protein, held together by unspecific hydrophobic interactions. Interestingly, truncated isoforms are entrapped exclusively in oligomers. Ab initio modeling of TDP-43 structure, molecular dynamics and molecular docking analysis indicate a differential accessibility of cysteine residues that contributes to aggregation propensity. We propose a model of TDP-43 aggregation involving cysteine-dependent and cysteine-independent stages that may constitute a starting point to devise strategies counteracting the formation of inclusions in TDP-43 proteinopathies. PMID:27317832

  11. Red blood cell (RBC) deformability, RBC aggregability and tissue oxygenation in hypertension.

    Science.gov (United States)

    Cicco, G; Pirrelli, A

    1999-01-01

    Arterial hypertension could be considered a progressive ischaemic syndrome interesting the macro and the microcirculation. In order to improve the clinical and therapeutic approach to the treatment of arterial hypertension, research has centered on blood flow to evaluate the different components and their very intricate relationships influencing the micro- and the macrocirculation. Of course the main problem is to study the link between the blood flow and the peripheral tissue oxygenation. During hypertension very important alterations in rheological, mechanical and biochemical characteristics of erythrocytes and of blood flow have been shown. It is very relevant the increase in blood viscosity, the decrease in red blood cell (RBC) deformability, the formation of RBC "rouleaux" and RBC aggregates. These hemorheological determinants can favour an increase of peripheral resistances and of arterial blood pressure, causing or worsening hypertension, a decrease in oxygen transport to tissue and peripheral perfusion, a decrease of the active exchange surface area in the microvasculature, especially in complicated hypertension. We have studied 320 patients: 123 with Essential Hypertension (EH) (M 59, F 64 aged 50 +/- 25 years); 81 with Secondary Hypertension (SH) without associated other pathologies influencing hemorheology (M 42, F 39 aged 48 +/- 20 years); 116 SH with other pathologies or conditions associated influencing hemorheology such as: diabetes, lipoidoproteinosis, obesity, smoking, HD, elderly, etc. (M 48, F 68 aged 46 +/- 20 years). Using a Laser-assisted Optical Rotational Red Cell Analyzer (LORCA) acc. to Hardeman (1994) we studied Elongation Index (EI) and aggregation kinetics of red blood cells in these patients. We also evaluated TcpO2 and TcpCO2 using a transcutaneous oxymeter (Microgas 7650, Kontron Instruments). In hypertensives we found a decrease in erythrocyte deformability (evaluated with EI), in erythrocyte aggregation time, a fibrinogenaemia

  12. Gap junction communication between cells aggregated on a cellulose-coated polystyrene: influence of connexin 43 phosphorylation.

    Science.gov (United States)

    Faucheux, N; Zahm, J M; Bonnet, N; Legeay, G; Nagel, M D

    2004-06-01

    The appropriate functioning of tissues and organ systems depends on intercellular communication such as gap junctions formed by connexin (Cx) protein channels between adjacent cells. We have previously shown that Swiss 3T3 cells aggregated on hydrophilic cellulose substratum Cuprophan (CU) establish short linear gap junctions composed of Cx 43 in cell surface plaques. This phenomenon seems to depend on the high intracellular cyclic AMP (cAMP) concentration triggered by attachment of the cells to CU. We have now used a cellulose-coated polystyrene inducing the same cell behaviour to analyse the gap junction communication between aggregated cells. The transfer of the dye Lucifer Yellow (LY) between cells showed that cells aggregated on cellulose substratum rapidly (within 90 min) establish functional gap junctions. Inhibitors of cAMP protein kinase (PKI) or protein kinase C (GF109203X) both inhibited the diffusion of LY between neighbouring cells. Western blot analysis showed that this change in permeability was correlated with a decrease in Cx 43 phosphorylation. Thus, cellulose substrata seem to induce cell-cell communication through Cx 43 phosphorylation modulated by PKA and PKC. To understand the mechanisms by which a substratum regulates gap junctional communication is critically important for the emerging fields of tissue engineering and biohybrid devices. PMID:14751734

  13. Formation of model hepatocellular aggregates in a hydrogel scaffold using degradable genipin crosslinked gelatin microspheres as cell carriers

    International Nuclear Information System (INIS)

    Primary hepatocyte is probably the preferred cell for cell therapy in liver regeneration. However, its non-ideal proliferation capacity and rapid loss of phenotype during 2D culture compromises the quality and quantity of the transplanted hepatocytes, resulting in variable success rates of this treatment. Many studies have shown that the formation of 3D hepatocellular spheroids aids in the maintenance of liver-specific functions in hepatocytes. However, many of the methodologies employed require a sophisticated set-up or specialized equipment which makes it uneconomical to scale up for clinical applications. In this study, we have developed dual-functioning genipin crosslinked gelatin microspheres that serve as cell carriers as well as porogens for delivering the model cells and also for creating cavities. The cells were first seeded onto genipin crosslinked gelatin microspheres for attachment, followed by encapsulation in alginate hydrogel. Collagenase, MMP-9, was introduced either in the culture media or mixed with alginate precursor solution to allow microsphere degradation for creating cavities within the gel bulk. Accordingly, the cells proliferate within the cavities, forming hepatocellular aggregates while the alginate hydrogel serves as a confinement, restricting the size and the shape of the aggregates to the size of the cavities. In addition, the final hepatocellular aggregates could be harvested from the system by removing the alginate hydrogel via citrate treatment. Therefore, this versatile platform not only has the advantage of injectability and simplicity, the cellular aggregates generated are in a controlled size and shape and can be extracted from the system. (paper)

  14. Ionizing Radiation Induces Macrophage Foam Cell Formation and Aggregation Through JNK-Dependent Activation of CD36 Scavenger Receptors

    International Nuclear Information System (INIS)

    Purpose: Irradiated arteries of cancer patients can be associated with atherosclerosis-like lesions containing cholesterol-laden macrophages (foam cells). Endothelial cell damage by irradiation does not completely explain the foam cell formation. We investigated the possible underlying mechanisms for ionizing radiation (IR)-induced foam cell formation. Methods and Materials: Human peripheral blood monocytes were activated by macrophage colony-stimulating factor and then treated with varying doses of IR in vitro in the absence of endothelial cells. Scavenger receptor expression and foam cell formation of IR-treated macrophages were investigated in the presence or absence of oxidized low-density lipoprotein. We also assessed the importance of mitogen-activated protein kinase activity in the macrophage colony-stimulating factor-activated human monocytes (macrophages) for the foam cell formation. Results: We found that IR treatment of macrophage colony-stimulating factor-activated human peripheral blood monocytes resulted in the enhanced expression of CD36 scavenger receptors and that cholesterol accumulated in the irradiated macrophages with resultant foam cell formation in the presence of oxidized low-density lipoprotein. Furthermore, when cultured on collagen gels, human macrophages formed large foam cell aggregates in response to IR. Antibodies against CD36 inhibited the IR-induced foam cell formation and aggregation, indicating that the IR-induced foam cell formation and the subsequent aggregation are dependent on functional CD36. In addition, we found that IR of human macrophages resulted in c-Jun N-terminal kinase activation and that c-Jun N-terminal kinase inhibition suppressed IR-induced CD36 expression and the subsequent foam cell formation and aggregation. Conclusion: Taken together, these results suggest that IR-induced foam cell formation is mediated by c-Jun N-terminal kinase-dependent CD36 activation

  15. Embryo aggregation does not improve the development of interspecies somatic cell nuclear transfer embryos in the horse.

    Science.gov (United States)

    Gambini, Andrés; De Stéfano, Adrián; Jarazo, Javier; Buemo, Carla; Karlanian, Florencia; Salamone, Daniel Felipe

    2016-09-01

    The low efficiency of interspecies somatic cell nuclear transfer (iSCNT) makes it necessary to investigate new strategies to improve embryonic developmental competence. Embryo aggregation has been successfully applied to improve cloning efficiency in mammals, but it remains unclear whether it could also be beneficial for iSCNT. In this study, we first compared the effect of embryo aggregation over in vitro development and blastocyst quality of porcine, bovine, and feline zona-free (ZF) parthenogenetic (PA) embryos to test the effects of embryo aggregation on species that were later used as enucleated oocytes donors in our iSCNT study. We then assessed whether embryo aggregation could improve the in vitro development of ZF equine iSCNT embryos after reconstruction with porcine, bovine, and feline ooplasm. Bovine- and porcine-aggregated PA blastocysts had significantly larger diameters compared with nonaggregated embryos. On the other hand, feline- and bovine-aggregated PA embryos had higher blastocyst cell number. Embryo aggregation of equine-equine SCNT was found to be beneficial for embryo development as we have previously reported, but the aggregation of three ZF reconstructed embryos did not improve embryo developmental rates on iSCNT. In vitro embryo development of nonaggregated iSCNT was predominantly arrested around the stage when transcriptional activation of the embryonic genome is reported to start on the embryo of the donor species. Nevertheless, independent of embryo aggregation, equine blastocyst-like structures could be obtained in our study using domestic feline-enucleated oocytes. Taken together, these results reported that embryo aggregation enhance in vitro PA embryo development and embryo quality but effects vary depending on the species. Embryo aggregation also improves, as expected, the in vitro embryo development of equine-equine SCNT embryos; however, we did not observe positive effects on equine iSCNT embryo development. Among oocytes

  16. Porphyrin Dye-Sensitized Zinc Oxide Aggregated Anodes for Use in Solar Cells.

    Science.gov (United States)

    Syu, Yu-Kai; Tingare, Yogesh; Lin, Shou-Yen; Yeh, Chen-Yu; Wu, Jih-Jen

    2016-01-01

    Porphyrin YD2-o-C8-based dyes were employed to sensitize room-temperature (RT) chemical-assembled ZnO aggregated anodes for use in dye-sensitized solar cells (DSSCs). To reduce the acidity of the YD2-o-C8 dye solution, the proton in the carboxyl group of a porphyrin dye was replaced with tetrabuthyl ammonium (TBA⁺) in this work. The short-circuit current density (Jsc) of the YD2-o-C8-TBA-sensitized ZnO DSSCs is higher than that of the YD2-o-C8-sensitized cells, resulting in the improvement of the efficiency of the YD2-o-C8-based ZnO DSSCs. With an appropriate incorporation of chenodeoxycholic acid (CDCA) as coadsorbate, the Jsc and efficiency of the YD2-o-C8-TBA-sensitized ZnO DSSC are enhanced due to the improvement of the incident-photon-to-current efficiency (IPCE) values in the wavelength range of 400-450 nm. Moreover, a considerable increase in Jsc is achieved by the addition of a light scattering layer in the YD2-o-C8-TBA-sensitized ZnO photoanodes. Significant IPCE enhancement in the range 475-600 nm is not attainable by tuning the YD2-o-C8-TBA sensitization processes for the anodes without light scattering layers. Using the RT chemical-assembled ZnO aggregated anode with a light scattering layer, an efficiency of 3.43% was achieved in the YD2-o-C8-TBA-sensitized ZnO DSSC. PMID:27527136

  17. Porphyrin Dye-Sensitized Zinc Oxide Aggregated Anodes for Use in Solar Cells

    Directory of Open Access Journals (Sweden)

    Yu-Kai Syu

    2016-08-01

    Full Text Available Porphyrin YD2-o-C8-based dyes were employed to sensitize room-temperature (RT chemical-assembled ZnO aggregated anodes for use in dye-sensitized solar cells (DSSCs. To reduce the acidity of the YD2-o-C8 dye solution, the proton in the carboxyl group of a porphyrin dye was replaced with tetrabuthyl ammonium (TBA+ in this work. The short-circuit current density (Jsc of the YD2-o-C8-TBA-sensitized ZnO DSSCs is higher than that of the YD2-o-C8-sensitized cells, resulting in the improvement of the efficiency of the YD2-o-C8-based ZnO DSSCs. With an appropriate incorporation of chenodeoxycholic acid (CDCA as coadsorbate, the Jsc and efficiency of the YD2-o-C8-TBA-sensitized ZnO DSSC are enhanced due to the improvement of the incident-photon-to-current efficiency (IPCE values in the wavelength range of 400–450 nm. Moreover, a considerable increase in Jsc is achieved by the addition of a light scattering layer in the YD2-o-C8-TBA-sensitized ZnO photoanodes. Significant IPCE enhancement in the range 475–600 nm is not attainable by tuning the YD2-o-C8-TBA sensitization processes for the anodes without light scattering layers. Using the RT chemical-assembled ZnO aggregated anode with a light scattering layer, an efficiency of 3.43% was achieved in the YD2-o-C8-TBA-sensitized ZnO DSSC.

  18. Weak glycolipid binding of a microdomain-tracer peptide correlates with aggregation and slow diffusion on cell membranes.

    Directory of Open Access Journals (Sweden)

    Tim Lauterbach

    Full Text Available Organized assembly or aggregation of sphingolipid-binding ligands, such as certain toxins and pathogens, has been suggested to increase binding affinity of the ligand to the cell membrane and cause membrane reorganization or distortion. Here we show that the diffusion behavior of the fluorescently tagged sphingolipid-interacting peptide probe SBD (Sphingolipid Binding Domain is altered by modifications in the construction of the peptide sequence that both result in a reduction in binding to ganglioside-containing supported lipid membranes, and at the same time increase aggregation on the cell plasma membrane, but that do not change relative amounts of secondary structural features. We tested the effects of modifying the overall charge and construction of the SBD probe on its binding and diffusion behavior, by Surface Plasmon Resonance (SPR; Biacore analysis on lipid surfaces, and by Fluorescence Correlation Spectroscopy (FCS on live cells, respectively. SBD binds preferentially to membranes containing the highly sialylated gangliosides GT1b and GD1a. However, simple charge interactions of the peptide with the negative ganglioside do not appear to be a critical determinant of binding. Rather, an aggregation-suppressing amino acid composition and linker between the fluorophore and the peptide are required for optimum binding of the SBD to ganglioside-containing supported lipid bilayer surfaces, as well as for interaction with the membrane. Interestingly, the strength of interactions with ganglioside-containing artificial membranes is mirrored in the diffusion behavior by FCS on cell membranes, with stronger binders displaying similar characteristic diffusion profiles. Our findings indicate that for aggregation-prone peptides, aggregation occurs upon contact with the cell membrane, and rather than giving a stronger interaction with the membrane, aggregation is accompanied by weaker binding and complex diffusion profiles indicative of heterogeneous

  19. Phase I North Central Cancer Treatment Group Trial-N9923 of escalating doses of twice-daily thoracic radiation therapy with amifostine and with alternating chemotherapy in limited stage small-cell lung cancer

    International Nuclear Information System (INIS)

    Purpose: The primary goal was to identify the maximum tolerable dose (MTD) of thoracic radiation therapy (TRT) that can be given with chemotherapy and amifostine for patients with limited-stage small-cell lung cancer (LSCLC). Methods and Materials: Treatment began with two cycles of topotecan (1 mg/m2) Days 1 to 5 and paclitaxel (175 mg/m2) Day 5 (every 3 weeks) given before and after TRT. The TRT began at 6 weeks. The TRT was given in 120 cGy fractions b.i.d. and the dose escalation (from 4,800 cGy, dose level 1, to 6,600 cGy, dose level 4) followed the standard 'cohorts of 3' design. The etoposide (E) (50 mg/day) and cisplatin (C) (3 mg/m2) were given i.v. before the morning TRT and amifostine (500 mg/day) was given before the afternoon RT. This was followed by prophylactic cranial irradiation (PCI). The dose-limiting toxicities (DLTs) were defined as Grade ≥4 hematologic, febrile neutropenia, esophagitis, or other nonhematologic toxicity, Grade ≥3 dyspnea, or Grade ≥2 pneumonitis. Results: Fifteen patients were evaluable for the Phase I portion of the trial. No DLTs were seen at dose levels 1 and 2. Two patients on dose level 4 experienced DLTs: 1 patient had a Grade 4 pneumonitis, dyspnea, fatigue, hypokalemia, and anorexia, and 1 patient had a Grade 5 hypoxia attributable to TRT. One of 6 patients on dose level 3 had a DLT, Grade 3 esophagitis. The Grade ≥3 toxicities seen in at least 10% of patients during TRT were esophagitis (53%), leukopenia (33%), dehydration (20%), neutropenia (13%), and fatigue (13%). The median survival was 14.5 months. Conclusion: The MTD of b.i.d. TRT was 6000 cGy (120 cGy b.i.d.) with EP and amifostine

  20. Protein aggregation and bioprocessing

    OpenAIRE

    Cromwell, Mary E. M.; Hilario, Eric; Jacobson, Fred

    2006-01-01

    Protein aggregation is a common issue encountered during manufacture of biotherapeutics. It is possible to influence the amount of aggregate produced during the cell culture and purification process by carefully controlling the environment (eg, media components) and implementing appro-priate strategies to minimize the extent of aggregation. Steps to remove aggregates have been successfully used at a manufacturing scale. Care should be taken when developing a process to monitor the compatibili...

  1. LEDGF1-326 Decreases P23H and Wild Type Rhodopsin Aggregates and P23H Rhodopsin Mediated Cell Damage in Human Retinal Pigment Epithelial Cells

    OpenAIRE

    Rinku Baid; Scheinman, Robert I; Toshimichi Shinohara; Singh, Dhirendra P; Kompella, Uday B.

    2011-01-01

    BACKGROUND: P23H rhodopsin, a mutant rhodopsin, is known to aggregate and cause retinal degeneration. However, its effects on retinal pigment epithelial (RPE) cells are unknown. The purpose of this study was to determine the effect of P23H rhodopsin in RPE cells and further assess whether LEDGF(1-326), a protein devoid of heat shock elements of LEDGF, a cell survival factor, reduces P23H rhodopsin aggregates and any associated cellular damage. METHODS: ARPE-19 cells were transiently transfect...

  2. Chemical Assembly of Zinc Oxide Aggregated Anodes on Plastic Substrates at Room Temperature for Flexible Dye-Sensitized Solar Cells

    International Nuclear Information System (INIS)

    Highlights: • The ZnO aggregates are chemically assembled on the ITO-PET substrate by the room-temperature chemical treatment of the drop-cast ZnO nanoparticle layer on the substrate. • The enhanced light scattering ability and superior electron transport property are measured in the ZnO aggregated anode. • A notable efficiency of 5.16% is achieved in the flexible dye-sensitized solar cell using the ZnO aggregated anode with a light scattering layer. • Good flexibility of the ZnO nanostructured anodes fabricated free of high-temperature treatment and mechanical compression is demonstrated. - Abstract: A notable efficiency of 5.16% is achieved in the flexible dye-sensitized solar cell (DSSC) using a ZnO aggregated anode with a light scattering layer facilely fabricated on the indium tin oxide (ITO) coated-polyethylene terephthalate (PET) substrate. The ZnO aggregates composed of ZnO nanoparticles (NPs) and room-temperature (RT) grown nanostructures are chemically assembled on the ITO-PET substrate by the RT chemical treatment of the drop-cast ZnO NP layer on the substrate. The enhanced light scattering ability and superior electron transport property are measured in the ZnO aggregated matrix anode. A ZnO particle layer is further drop-cast on the ZnO aggregated matrix anode followed by another RT chemical treatment to form the light scattering layer. Dynamics of electron transport and recombination measurements indicate that an efficient electron collection is performed in the flexible ZnO anode fabricated free of high-temperature treatment and mechanical compression. Moreover, efficient photovoltaic performances are also monitored in both concave-downward and concave-upward bending configurations of the ZnO DSSCs, demonstrating the good flexibility of the ZnO nanostructured anodes

  3. Inhibition of Pathogenic Mutant SOD1 Aggregation in Cultured Motor Neuronal Cells by Prevention of Its SUMOylation on Lysine 75.

    Science.gov (United States)

    Dangoumau, Audrey; Marouillat, Sylviane; Burlaud Gaillard, Julien; Uzbekov, Rustem; Veyrat-Durebex, Charlotte; Blasco, Hélène; Arnoult, Christophe; Corcia, Philippe; Andres, Christian R; Vourc'h, Patrick

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective death of motor neurons. Mutations in the SOD1 gene encoding the superoxide dismutase 1 are present in 15% of familial ALS cases and in 2% of sporadic cases. These mutations are associated with the formation of SOD1-positive aggregates. The mechanisms of aggregation remain unknown, but posttranslational modifications of SOD1 may be involved. Here, we report that NSC-34 motor neuronal cells expressing mutant SOD1 contained aggregates positive for small ubiquitin modifier-1 (SUMO-1), and in parallel a reduced level of free SUMO-1. CLEM (correlative light and electron microscopy) analysis showed nonorganized cytosolic aggregates for all mutations tested (SOD1A4V, SOD1V31A, and SOD1G93C). We next show that preventing the SUMOylation of mutant SOD1 by the substitution of lysine 75, the SUMOylation site of SOD1, significantly reduces the number of motor neuronal cells with aggregates. These results support the need for further research on the SUMOylation pathways, which may be a potential therapeutic target in ALS. PMID:26605782

  4. Effect of ionic and non-ionic contrast media on aggregation of red blood cells in vitro

    International Nuclear Information System (INIS)

    Fresh human blood without additives, and contrast medium were mixed and examined immediately by light microscopy in a non-flowing state. Sodium meglumine diatrizoate, meglumine diatrizoate, meglumine iodamide, sodium meglumine ioxaglate, iopromide, iopamidol, iohexol, and metrizamide were tested in concentrations of 300 mgI/ml. Physiologic saline and 5% glucose were used as controls. All media were tested in a randomized order with blood samples from 23 volunteers. No aggregation was detected in physiologic saline, and few rouleaux were found in ionic contrast media. Irregular red cell aggregates were found in all low-osmolal contrast media: in 17% of the specimens in ioxaglate, in 52% in metrizamide, and in 78 to 100% in other non-ionic media. Irregular aggregates were seen in all specimens with glucose. It remains to be domonstrated whether or not the irregular aggregation of human red cells in non-ionic contrast media has clinical significance. Iohexol was also tested with blood samples from several laboratory animals, but in nearly every case no aggregates were found. Results of animal experiments or tests with animal blood seem to be poorly applicable to man. (orig.)

  5. Effect of ionic and non-ionic contrast media on aggregation of red blood cells in vitro. A preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Raininko, R.; Ylinen, S.L.

    Fresh human blood without additives, and contrast medium were mixed and examined immediately by light microscopy in a non-flowing state. Sodium meglumine diatrizoate, meglumine diatrizoate, meglumine iodamide, sodium meglumine ioxaglate, iopromide, iopamidol, iohexol, and metrizamide were tested in concentrations of 300 mgI/ml. Physiologic saline and 5% glucose were used as controls. All media were tested in a randomized order with blood samples from 23 volunteers. No aggregation was detected in physiologic saline, and few rouleaux were found in ionic contrast media. Irregular red cell aggregates were found in all low-osmolal contrast media: in 17% of the specimens in ioxaglate, in 52% in metrizamide, and in 78 to 100% in other non-ionic media. Irregular aggregates were seen in all specimens with glucose. It remains to be domonstrated whether or not the irregular aggregation of human red cells in non-ionic contrast media has clinical significance. Iohexol was also tested with blood samples from several laboratory animals, but in nearly every case no aggregates were found. Results of animal experiments or tests with animal blood seem to be poorly applicable to man.

  6. An in vitro model of granuloma-like cell aggregates substantiates early host immune responses against Mycobacterium massiliense infection

    Science.gov (United States)

    Je, Sungmo; Quan, Hailian; Na, Yirang; Cho, Sang-Nae; Kim, Bum-Joon

    2016-01-01

    ABSTRACT Mycobacterium massiliense (M. mass), belonging to the M. abscessus complex, is a rapidly growing mycobacterium that is known to cause tuberculous-like lesions in humans. To better understand the interaction between host cells and M. mass, we used a recently developed in vitro model of early granuloma-like cell aggregates composed of human peripheral blood mononuclear cells (PBMCs). PBMCs formed granuloma-like, small and rounded cell aggregates when infected by live M. mass. Microscopic examination showed monocytes and macrophages surrounded by lymphocytes, which resembled cell aggregation induced by M. tuberculosis (M. tb). M. mass-infected PBMCs exhibited higher expression levels of HLA-DR, CD86 and CD80 on macrophages, and a significant decrease in the populations of CD4+ and CD8+ T cells. Interestingly, low doses of M. mass were sufficient to infect PBMCs, while active host cell death was gradually induced with highly increased bacterial loads, reflecting host destruction and dissemination of virulent rapid-growing mycobacteria (RGM). Collectively, this in vitro model of M. mass infection improves our understanding of the interplay of host immune cells with mycobacteria, and may be useful for developing therapeutics to control bacterial pathogenesis. PMID:27489303

  7. Remodelling in the array of cell aggregates in somatotopic representation of the facial vibrissae through the trigeminal sensory system of the mouse.

    Science.gov (United States)

    Yamakado, M

    1995-11-01

    The disposition of the facial vibrissae of the mouse is represented as a matrix-like array of cell aggregates in rows and columns at every station of the whisker-to-barrel pathway. In order to evaluate the role of each station in this pathway, lesions were made in the facial vibrissae of the mystacial group on P0-P3, and the animals were sacrificed on P8. The effects of the lesions on the cell aggregates in the array were analyzed by using cytochrome oxidase and gallocyanin cell-staining methods. Division of cell aggregates in the array was controlled by row basis interactions through the pathway up to the cerebral cortex. In this organization, affected cell aggregates which corresponded to the damaged vibrissae were eliminated and/or fused together in the array of the thalamic relay nucleus. On the basis of thalamic modification, the final array of cell aggregates was remodelled in the cerebral cortex. In contrast, affected cell aggregates remained degenerative spaces at the original sites in the array in relation to the damaged vibrissae in the brain stem trigeminal nuclear complex. These results indicate that a protoframework with row basis orientation for the division of cell aggregates is prepared in every station of the pathway at the time of lesioning, and adjustment of subcortical alterations in the thalamic relay nucleus is a decisive process to let the cerebral cortex remodel the topographic array of cell aggregates. PMID:8602280

  8. Neurobiology of escalated aggression and violence

    NARCIS (Netherlands)

    Miczek, Klaus A.; de Almeida, Rosa M. M.; Kravitz, Edward A.; Rissman, Emilie F.; de Boer, Sietse F.; Raine, Adrian

    2007-01-01

    Psychopathological violence in criminals and intense aggression in fruit flies and rodents are studied with novel behavioral, neurobiological, and genetic approaches that characterize the escalation from adaptive aggression to violence. One goal is to delineate the type of aggressive behavior and it

  9. Dose escalation of accelerated hypofractionated three-dimensional conformal radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin chemotherapy in unresectable stage III non-small-cell lung cancer: a phase I trial

    International Nuclear Information System (INIS)

    Accelerated hypofractionated radiotherapy can shorten total treatment time and overcome the accelerated repopulation of tumour cells during radiotherapy. This therapeutic approach has demonstrated good efficacy in the treatment of locally advanced non-small-cell lung cancer (NSCLC). However, the optimal fractionation scheme remains uncertain. The purpose of this phase I trial was to explore the maximum tolerated dose (MTD) of accelerated hypofractionated three-dimensional conformal radiotherapy (3-DCRT) (at 3 Gy/fraction) administered in combination with concurrent vinorelbine (NVB) and carboplatin (CBP) chemotherapy for unresectable stage III NSCLC. Previously untreated cases of unresectable stage III NSCLC received accelerated hypofractionated 3-DCRT, delivered at 3 Gy per fraction, once daily, with five fractions per week. The starting dose was 66 Gy and an increment of 3 Gy was utilized. Higher doses continued to be tested in patient groups until the emergence of dose-limiting toxicity (DLT). The MTD was regarded as the dose that was one step below the dose at which DLT occurred. Patients received at least one cycle of a concurrent two-drug chemotherapy regimen of NVB and CBP. A total of 13 patients were enrolled and progressed through three dose escalation groups: 66 Gy, 69 Gy, and 72 Gy. No treatment-related deaths occurred. The major adverse events included radiation oesophagitis, radiation pneumonitis, and neutropenia. Nausea, fatigue, and anorexia were commonly observed, although the magnitude of these events was typically relatively minor. Among the entire group, four instances of DLT were observed, including two cases of grade 3 radiation oesophagitis, one case of grade 3 radiation pneumonitis, and one case of grade 4 neutropenia. All of these cases of DLT occurred in the 72 Gy group. Therefore, 72 Gy was designated as the DLT dose level, and the lower dose of 69 Gy was regarded as the MTD. For unresectable stage III NSCLC 69 Gy (at 3 Gy/fraction) was

  10. Thermal protein denaturation and protein aggregation in cells made thermotolerant by various chemicals: role of heat shock proteins.

    Science.gov (United States)

    Kampinga, H H; Brunsting, J F; Stege, G J; Burgman, P W; Konings, A W

    1995-08-01

    Thermotolerance (TT) induced by sodium arsenite (A-TT: 100 microM, 1 h, 37 degrees C) was compared to heat-induced thermotolerance (H-TT: 15 min, 44 degrees C) using HeLa S3 cells. All four pretreatments led to comparable levels of thermotolerance and also induced resistance to arsenite-, ethanol-, and diamide-induced toxicity (clonogenic ability). Stress-induced expression of the major heat shock proteins (hsp27, hsc70(p73), hsp70(p72), and hsp90) was generally highest in H-TT cells and lowest in A-TT cells. Interestingly, the four types of TT cells showed distinct differences in certain aspects of resistance against thermal protein damage. Thermal protein denaturation and aggregation determined in isolated cellular membrane fractions was found to be attenuated when they were isolated from H-TT and A-TT cells but not when isolated from E-TT and D-TT cells. The heat resistance in the proteins of the membrane fraction corresponded with elevated levels of hsp70(p72) associated with the isolated membrane fractions. In the nuclear fraction, only marginal (not significant) attenuation of the formation of protein aggregates (as determined by TX-100 (in)solubility) was observed. However, the postheat recovery from heat-induced protein aggregation in the nucleus was faster in H-TT, E-TT, and D-TT cells, but not in A-TT cells. Despite the fact that elevated levels of hsp27, hsp70(p73), and hsp70(p72) were found in the TX-100 insoluble nuclear fraction derived from all TT cells, no correlation was found with the degree of resistance in terms of the accelerated recovery from nuclear protein aggregation. The only correlation between accelerated recovery from nuclear protein aggregates was that with total cellular levels of hsp27. The data indicate that heat-induced loss of clonogenic ability may be a multitarget rather than a single target event. A threshold of damage may exist in cells after exposure to heat; multiple sets of proteins in (different compartments of) the cell

  11. In vitro aggregation behavior of a non-amyloidogenic λ light chain dimer deriving from U266 multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    Paolo Arosio

    Full Text Available Excessive production of monoclonal light chains due to multiple myeloma can induce aggregation-related disorders, such as light chain amyloidosis (AL and light chain deposition diseases (LCDD. In this work, we produce a non-amyloidogenic IgE λ light chain dimer from human mammalian cells U266, which originated from a patient suffering from multiple myeloma, and we investigate the effect of several physicochemical parameters on the in vitro stability of this protein. The dimer is stable in physiological conditions and aggregation is observed only when strong denaturating conditions are applied (acidic pH with salt at large concentration or heating at melting temperature T(m at pH 7.4. The produced aggregates are spherical, amorphous oligomers. Despite the larger β-sheet content of such oligomers with respect to the native state, they do not bind Congo Red or ThT. The impossibility to obtain fibrils from the light chain dimer suggests that the occurrence of amyloidosis in patients requires the presence of the light chain fragment in the monomer form, while dimer can form only amorphous oligomers or amorphous deposits. No aggregation is observed after denaturant addition at pH 7.4 or at pH 2.0 with low salt concentration, indicating that not a generic unfolding but specific conformational changes are necessary to trigger aggregation. A specific anion effect in increasing the aggregation rate at pH 2.0 is observed according to the following order: SO(4(-≫Cl(->H(2PO(4(-, confirming the peculiar role of sulfate in promoting protein aggregation. It is found that, at least for the investigated case, the mechanism of the sulfate effect is related to protein secondary structure changes induced by anion binding.

  12. Cluster–cluster aggregation with particle replication and chemotaxy: a simple model for the growth of animal cells in culture

    International Nuclear Information System (INIS)

    Aggregation of animal cells in culture comprises a series of motility, collision and adhesion processes of basic relevance for tissue engineering, bioseparations, oncology research and in vitro drug testing. In the present paper, a cluster–cluster aggregation model with stochastic particle replication and chemotactically driven motility is investigated as a model for the growth of animal cells in culture. The focus is on the scaling laws governing the aggregation kinetics. Our simulations reveal that in the absence of chemotaxy the mean cluster size and the total number of clusters scale in time as stretched exponentials dependent on the particle replication rate. Also, the dynamical cluster size distribution functions are represented by a scaling relation in which the scaling function involves a stretched exponential of the time. The introduction of chemoattraction among the particles leads to distribution functions decaying as power laws with exponents that decrease in time. The fractal dimensions and size distributions of the simulated clusters are qualitatively discussed in terms of those determined experimentally for several normal and tumoral cell lines growing in culture. It is shown that particle replication and chemotaxy account for the simplest cluster size distributions of cellular aggregates observed in culture

  13. Effects of 2-methoxyestradiol on proliferation, apoptosis and PET-tracer uptake in human prostate cancer cell aggregates

    Energy Technology Data Exchange (ETDEWEB)

    Davoodpour, Padideh; Bergstroem, Mats; Landstroem, Marene E-mail: Marene.Landstrom@LICR.uu.se

    2004-10-01

    The purpose of this study was to investigate the potential use of PET in vivo to record cytotoxic effects of 2-methoxyestradiol (2-ME), an endogenous metabolite of 17{beta}-estradiol. The anti-proliferative and pro-apoptotic effects of 2-ME on human prostate cancer cell (PC3) aggregates in vitro, were correlated with the uptake of fluoro-deoxy-D-glucose, FMAU and choline labelled with {sup 18}F, {sup 11}C, or {sup 3}H. 2-ME clearly reduced growth of PC3 aggregates and induced apoptosis in a dose-dependent manner. However, the uptake of the putative proliferation markers {sup 11}C-FMAU or {sup 3}H-choline failed to record the growth inhibitory effects of 2-ME on PC3 cell aggregates. The uptake of {sup 18}F-FDG was used as a marker for effects on cellular metabolism and also failed to show any dose-dependent effects in PC3 aggregates. The use of these PET-tracers in vivo is therefore not recommended in order to evaluate the cytotoxic effects of 2-ME on human prostate cancer cells.

  14. Aggregation of gold nanoparticles followed by methotrexate release enables Raman imaging of drug delivery into cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Durgadas, C. V.; Sharma, C. P.; Paul, W.; Rekha, M. R. [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Biosurface Technology Division (India); Sreenivasan, K., E-mail: sreeni@sctimst.ac.in [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Laboratory for Polymer Analysis, Biomedical Technology Wing (India)

    2012-09-15

    This study refers an aqueous synthesis of methotrexate (MTX)-conjugated gold nanoparticles (GNPs), their interaction with HepG2 cells, and the use of Raman imaging to observe cellular internalization and drug delivery. GNPs of average size 3.5-5 nm were stabilized using the amine terminated bifunctional biocompatible copolymer and amended by conjugating MTX, an anticancer drug. The nanoparticles were released MTX at a faster rate in acidic pH and subsequently found to form aggregates. The Raman signals of cellular components were found to be enhanced by the aggregated particles enabling the mapping to visualize site-specific drug delivery. The methodology seems to have potential in optimizing the characteristics of nanodrug carriers for emptying the cargo precisely at specified sites.Graphical AbstractDrug release induced particle aggregation enhances Raman signals to aid in imaging.

  15. Aggregation of gold nanoparticles followed by methotrexate release enables Raman imaging of drug delivery into cancer cells

    International Nuclear Information System (INIS)

    This study refers an aqueous synthesis of methotrexate (MTX)-conjugated gold nanoparticles (GNPs), their interaction with HepG2 cells, and the use of Raman imaging to observe cellular internalization and drug delivery. GNPs of average size 3.5–5 nm were stabilized using the amine terminated bifunctional biocompatible copolymer and amended by conjugating MTX, an anticancer drug. The nanoparticles were released MTX at a faster rate in acidic pH and subsequently found to form aggregates. The Raman signals of cellular components were found to be enhanced by the aggregated particles enabling the mapping to visualize site-specific drug delivery. The methodology seems to have potential in optimizing the characteristics of nanodrug carriers for emptying the cargo precisely at specified sites.Graphical AbstractDrug release induced particle aggregation enhances Raman signals to aid in imaging.

  16. The Effect of Calcination Temperature on the Performance of TiO2 Aggregates-based Dye Solar Cells (DSCs)

    International Nuclear Information System (INIS)

    In this paper, the effect of calcination temperature on the physicochemical properties of synthesized TiO2 aggregates and their influence on overall light conversion efficiency of dye solar cell (DSc) were investigated. Samples of TiO2 aggregates (mean size of 0.45 μm) composing of nano crystallites (10-40 nm) were synthesized through hydrolysis of dilute titanium alkoxide in ethanol. Phase and microstructure of the TiO2 obtained have been characterized using FESEM, XRD and UV-Vis spectroscopy. I-V characterization shows that TiO2 aggregates based DSC demonstrated better performance compared to nanoparticles (P-25)-based DSC. The optimum calcination temperature was found to be about 500 degree Celsius with efficiency of 4.456 %, which is 30 % increment compared to P-25-based DSC under the same condition. (author)

  17. Individual aggregates of amyloid beta induce temporary calcium influx through the cell membrane of neuronal cells

    Science.gov (United States)

    Drews, Anna; Flint, Jennie; Shivji, Nadia; Jönsson, Peter; Wirthensohn, David; De Genst, Erwin; Vincke, Cécile; Muyldermans, Serge; Dobson, Chris; Klenerman, David

    2016-01-01

    Local delivery of amyloid beta oligomers from the tip of a nanopipette, controlled over the cell surface, has been used to deliver physiological picomolar oligomer concentrations to primary astrocytes or neurons. Calcium influx was observed when as few as 2000 oligomers were delivered to the cell surface. When the dosing of oligomers was stopped the intracellular calcium returned to basal levels or below. Calcium influx was prevented by the presence in the pipette of the extracellular chaperone clusterin, which is known to selectively bind oligomers, and by the presence a specific nanobody to amyloid beta. These data are consistent with individual oligomers larger than trimers inducing calcium entry as they cross the cell membrane, a result supported by imaging experiments in bilayers, and suggest that the initial molecular event that leads to neuronal damage does not involve any cellular receptors, in contrast to work performed at much higher oligomer concentrations. PMID:27553885

  18. Effects of methylmercury upon dissociated embryonic rat brain cells in rotation-mediated re-aggregation culture

    Energy Technology Data Exchange (ETDEWEB)

    Choi, B.H.; Ahn, B.T. (Univ. of California, Irvine (USA))

    1989-02-09

    In order to test the hypothesis that methylmercury poisoning disrupts the organization and differentiation of the developing brain, mechanically dissociated cells from embryonic rat cerebra (E-17) and grown in rotation-mediated aggregation cultures were exposed varying concentrations (0.1, 0.2, and 0.5 {mu}M) of methylmercuric chloride (MMC) in F-12 medium containing 5% fetal calf and 5% horse sera. Controls received physiological saline in place of MMC. Cultures were harvested at 1, 2, 3, 7, 14 and 21 days and examined by phase and EM, radioautography, and immunocytochemistry. Although both control and MMC-exposed cells formed aggregates within 24 hours, the latter showed disaggregation of cell clumps at 48 hours and failure to reaggregate thereafter, whereas, in control cultures, there was progressive aggregation with EM evidence of differentiation. In control cultures, peripherally situated astrocytes extended their processes around and into the clumps, thereby maintaining the integrity of the clumps. Direct toxic damage to astrocytes interferes with this integrity and appear to play a major role in the disaggregation and failure of reaggregation. Preservation of the 3H-TdR labeling index in Hg-exposed cells despite disaggregation and cytotoxicity suggests that cells proliferation continues at the levels of Hg concentrations used while reaggregation is severely affected.

  19. Imaging Alzheimer's disease-related protein aggregates in human cells using a selenium label

    Energy Technology Data Exchange (ETDEWEB)

    McGuire, E K; McComb, D W; Porter, A E [Department of Materials, Imperial College, Exhibition Rd, London SW7 2AZ (United Kingdom); Motskin, M [Department of Anatomy, University of Cambridge, Downing St, Cambridge CB2 3DY (United Kingdom); Knowles, T P J [Nanoscience Centre, University of Cambridge, JJ Thomson Ave, Cambridge, CB3 0FF (United Kingdom); Dobson, C M, E-mail: e.mcguire07@imperial.ac.u [Department of Chemistry, University of Cambridge, Lensfield Rd, Cambridge CB2 1EW (United Kingdom)

    2010-07-01

    The aberrant folding and subsequent aggregation of proteins and peptides is associated with a range of pathological conditions from the systemic amyloidoses to neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. While this link is well established there is a lack of understanding of the exact role protein aggregates play in disease pathogenesis. Part of the reason for this is that it has proved extremely challenging to characterise the localisation and structure of amyloid fibrils within the cellular environment due to a lack of contrast between the carbon rich protein aggregates and the carbon rich cell. We report a novel method for visualising Alzheimer's disease-related amyloid fibrils inside human cells without the use of invasive or unreliable stains or tags. The naturally occurring sulfur atom in the amyloid-{beta} peptide is replaced with a selenium atom, a heavier element in the same group of the periodic table of elements. Using high angle annular dark field (HAADF) in a scanning transmission electron microscopy (STEM) the selenium-labelled aggregates can be identified within the cellular environment.

  20. Men with Sickle Cell Anemia and Priapism Exhibit Increased Hemolytic Rate, Decreased Red Blood Cell Deformability and Increased Red Blood Cell Aggregate Strength

    Science.gov (United States)

    Cita, Kizzy-Clara; Brureau, Laurent; Lemonne, Nathalie; Billaud, Marie; Connes, Philippe; Ferdinand, Séverine; Tressières, Benoit; Tarer, Vanessa; Etienne-Julan, Maryse; Blanchet, Pascal; Elion, Jacques; Romana, Marc

    2016-01-01

    Objectives To investigate the association between priapism in men with sickle cell anemia (SCA) and hemorheological and hemolytical parameters. Materials and Methods Fifty-eight men with SCA (median age: 38 years) were included; 28 who had experienced priapism at least once during their life (priapism group) and 30 who never experienced this complication (control group). Twenty-two patients were treated with hydroxycarbamide, 11 in each group. All patients were at steady state at the time of inclusion. Hematological and biochemical parameters were obtained through routine procedures. The Laser-assisted Optical Rotational Cell Analyzer was used to measure red blood cell (RBC) deformability at 30 Pa (ektacytometry) and RBC aggregation properties (laser backscatter versus time). Blood viscosity was measured at a shear rate of 225 s-1 using a cone/plate viscometer. A principal component analysis was performed on 4 hemolytic markers (i.e., lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT), total bilirubin (BIL) levels and reticulocyte (RET) percentage) to calculate a hemolytic index. Results Compared to the control group, patients with priapism exhibited higher ASAT (p = 0.01), LDH (p = 0.03), RET (p = 0.03) levels and hemolytic indices (p = 0.02). Higher RBC aggregates strength (p = 0.01) and lower RBC deformability (p = 0.005) were observed in patients with priapism compared to controls. After removing the hydroxycarbamide-treated patients, RBC deformability (p = 0.01) and RBC aggregate strength (p = 0.03) were still different between the two groups, and patients with priapism exhibited significantly higher hemolytic indices (p = 0.01) than controls. Conclusion Our results confirm that priapism in SCA is associated with higher hemolytic rates and show for the first time that this complication is also associated with higher RBC aggregate strength and lower RBC deformability. PMID:27145183

  1. Men with Sickle Cell Anemia and Priapism Exhibit Increased Hemolytic Rate, Decreased Red Blood Cell Deformability and Increased Red Blood Cell Aggregate Strength.

    Directory of Open Access Journals (Sweden)

    Kizzy-Clara Cita

    Full Text Available To investigate the association between priapism in men with sickle cell anemia (SCA and hemorheological and hemolytical parameters.Fifty-eight men with SCA (median age: 38 years were included; 28 who had experienced priapism at least once during their life (priapism group and 30 who never experienced this complication (control group. Twenty-two patients were treated with hydroxycarbamide, 11 in each group. All patients were at steady state at the time of inclusion. Hematological and biochemical parameters were obtained through routine procedures. The Laser-assisted Optical Rotational Cell Analyzer was used to measure red blood cell (RBC deformability at 30 Pa (ektacytometry and RBC aggregation properties (laser backscatter versus time. Blood viscosity was measured at a shear rate of 225 s-1 using a cone/plate viscometer. A principal component analysis was performed on 4 hemolytic markers (i.e., lactate dehydrogenase (LDH, aspartate aminotransferase (ASAT, total bilirubin (BIL levels and reticulocyte (RET percentage to calculate a hemolytic index.Compared to the control group, patients with priapism exhibited higher ASAT (p = 0.01, LDH (p = 0.03, RET (p = 0.03 levels and hemolytic indices (p = 0.02. Higher RBC aggregates strength (p = 0.01 and lower RBC deformability (p = 0.005 were observed in patients with priapism compared to controls. After removing the hydroxycarbamide-treated patients, RBC deformability (p = 0.01 and RBC aggregate strength (p = 0.03 were still different between the two groups, and patients with priapism exhibited significantly higher hemolytic indices (p = 0.01 than controls.Our results confirm that priapism in SCA is associated with higher hemolytic rates and show for the first time that this complication is also associated with higher RBC aggregate strength and lower RBC deformability.

  2. Scenarios of nuclear escalation dominance and vulnerability

    OpenAIRE

    Tritten, James John

    1988-01-01

    This document examines the role of strategic missile - carrying submarines in deterrence and mission of attacking these forces during the conventional phase of a war. Strategies considered include wars originating in varying regions. Included is a discussion of varying locations for submarine deployments impacting on potential Antisubmarine Warfare campaign. Escalation considerations include vertical, horizontal, and time. It concludes with analysis of possible arms control regulations. (KR)

  3. India's Nuclear Options and Escalation Dominance

    OpenAIRE

    Dalton, Toby; Perkovich, George

    2016-01-01

    Since the early 2000s, Indian strategists have wrestled with the challenge of motivating Pakistan to demobilize anti-India terrorist groups while managing the potential for conflict escalation during a crisis. The growing prominence of nuclear weapons in Pakistan’s national security strategy casts a shadow of nuclear use over any potential military strategy India might consider to strike this balance. However, augmenting its nuclear options with tactical nuclear weapons is u...

  4. Substituted perylene diimides as electron acceptors in organic solar cells: Suppressing aggregate formation to increase device efficiency

    International Nuclear Information System (INIS)

    Perylene diimide (PDI) is a promising electron acceptor material for high open circuit voltage bulk heterojunction organic solar cells. However, many PDI molecules have the drawback of strong aggregation leading to intermolecular excited state formation that results in exciton trapping. These traps can effectively limit the diffusion of excitons to the interface where charge separation occurs and thus strongly reduce the charge generation efficiency. In this contribution we study the influence of substitution of PDI molecules with side groups attached to the terminal and to the perylene core positions on the formation of aggregates. In particular transient photoluminescence and absorption spectroscopy are used to probe the impact of aggregation on the dynamics of charge generation and recombination in bulk heterojunction solar cells. Besides, AFM, x-ray and solid state NMR techniques are used to get further insight into the solid state morphology of polymer: PDI blends on different length scales. Finally, we correlate the photophysical properties of the PDI derivatives with the efficiency of bulk heterojunction organic solar cells and present unprecedented efficiencies from polymer: PDI solar cells.

  5. Enhanced expression of Aggrus (T1alpha/podoplanin), a platelet-aggregation-inducing factor in lung squamous cell carcinoma.

    Science.gov (United States)

    Kato, Yukinari; Kaneko, Mika; Sata, Makoto; Fujita, Naoya; Tsuruo, Takashi; Osawa, Motoki

    2005-01-01

    Aggrus (T1alpha/podoplanin, known as a specific marker for type I alveolar cells or lymphatic endothelial cells) is a transmembrane sialoglycoprotein that aggregates platelets. Previously, we showed that upregulated expression of Aggrus occurs in colorectal tumors or testicular tumors and could be associated with platelet-aggregating activity and metastatic ability. In testicular tumors, Aggrus is specifically expressed in seminoma. The present study investigates Aggrus expression in human primary lung cancer tissues of different types. Microarray analysis demonstrated that aggrus was significantly expressed in squamous cell carcinoma (10/15; 66.7%). Immunohistochemical analysis also showed that the incidence of positive staining in sections of squamous cell carcinoma (7/8; 87.5%) was higher than that in adenocarcinoma (2/13; 15.4%). Furthermore, Aggrus expression was detected in a squamous cell carcinoma cell line, NCI-H226, by real-time PCR. These findings indicated that overexpression of Aggrus occurred in squamous cell carcinoma of the lung. Therefore, Aggrus could be a useful diagnostic marker for squamous cell carcinoma of the lung. PMID:16006773

  6. Mild exposure of RIN-5F β-cells to human islet amyloid polypeptide aggregates upregulates antioxidant enzymes via NADPH oxidase-RAGE: An hormetic stimulus

    Directory of Open Access Journals (Sweden)

    Elisabetta Borchi

    2014-01-01

    Full Text Available The presence of amyloid aggregates of human islet amyloid polypeptide (hIAPP, a hallmark of type 2 diabetes, contributes to pancreatic β-cell impairment, where oxidative stress plays a key role. A contribution of NADPH oxidase to reactive oxygen species (ROS generation after cell exposure to micromolar concentrations of hIAPP aggregates has been suggested. However, little is known about β-cells exposure to lower amounts of hIAPP aggregates, similar to those found in human pancreas. Thus, we aimed to investigate the events resulting from RIN-5F cells exposure to nanomolar concentrations of toxic hIAPP aggregates. We found an early and transient rise of NADPH oxidase activity resulting from increased Nox1 expression following the engagement of receptor for advanced glycation end-products (RAGE by hIAPP aggregates. Unexpectedly, NADPH oxidase activation was not accompanied by a significant ROS increase and the lipoperoxidation level was significantly reduced. Indeed, cell exposure to hIAPP aggregates affected the antioxidant defences, inducing a significant increase of the expression and activity of catalase and glutathione peroxidase. We conclude that exposure of pancreatic β-cells to nanomolar concentrations of hIAPP aggregates for a short time induces an hormetic response via the RAGE-Nox1 axis; the latter stimulates the enzymatic antioxidant defences that preserve the cells against oxidative stress damage.

  7. [Analysis of proteins synthesized in aggregates of dissociated blastula and gastrula cells of Pleurodeles waltlii (Amphibia, urodela) by electrophoresis in polyacrylamide gradients].

    Science.gov (United States)

    Boucaut, J C; Desvaux, F X

    1976-09-20

    The protein synthesis manifested by aggregates of blastula and gastrula dissociated cells were studied by means of polyacylamide gradient gel electrophoresis. This method permits a comparative analysis of protein electrophoretic mobilities in aggregates and controls. In all cases, the data obtained establish the identity of protein banding and confirm an egg laying polymorphism. PMID:825304

  8. A Phase I Study of Reduced-Intensity Conditioning and Allogeneic Stem Cell Transplantation Followed by Dose Escalation of Targeted Consolidation Immunotherapy with Gemtuzumab Ozogamicin in Children and Adolescents with CD33(+) Acute Myeloid Leukemia.

    Science.gov (United States)

    Zahler, Stacey; Bhatia, Monica; Ricci, Angela; Roy, Sumith; Morris, Erin; Harrison, Lauren; van de Ven, Carmella; Fabricatore, Sandra; Wolownik, Karen; Cooney-Qualter, Erin; Baxter-Lowe, Lee Ann; Luisi, Paul; Militano, Olga; Kletzel, Morris; Cairo, Mitchell S

    2016-04-01

    Myeloablative conditioning and allogeneic hematopoietic stem cell transplant (alloHSCT) in children with acute myeloid leukemia (AML) in first complete remission (CR1) may be associated with significant acute toxicity and late effects. Reduced-intensity conditioning (RIC) and alloHSCT in children is safe, feasible, and may be associated with less adverse effects. Gemtuzumab ozogamicin (GO) induces a response in 30% of patients with CD33(+) relapsed/refractory AML. The dose of GO is significantly lower when combined with chemotherapy. We examined the feasibility and toxicity of RIC alloHSCT followed by GO targeted immunotherapy in children with CD33(+) AML in CR1/CR2. Conditioning consisted of fludarabine 30 mg/m(2) × 6 days, busulfan 3.2 to 4 mg/kg × 2 days ± rabbit antithymocyte globulin 2 mg/kg × 4 days followed by alloHSCT from matched related/unrelated donors. GO was administered ≥60 days after alloHSCT in 2 doses (8 weeks apart), following a dose-escalation design (4.5, 6, 7.5, and 9 mg/m(2)). Fourteen patients with average risk AML received RIC alloHSCT and post-GO consolidation: median age 13.5 years at transplant (range, 1 to 21), male-to-female 8:6, and disease status at alloHSCT 11 CR1 and 3 CR2. Eleven patients received alloHSCT from 5-6/6 HLA-matched family donors: 8 received peripheral blood stem cells, 2 received bone marrow, and 1 received related cord blood transplantation. Three patients received an unrelated allograft (two 4-5/6 and one 9/10) from unrelated cord blood unit and bone marrow, respectively. Neutrophil and platelet engraftment was observed in all assessable patients (100%), achieved at median 15.5 days (range, 7 to 31) and 21 days (range, 10 to 52), respectively. Three patients received GO at dose level 1 (4.5 mg/m(2) per dose), 5 at dose level 2 (6 mg/m(2) per dose), 3 at dose level 3 (7.5 mg/m(2) per dose), and 3 at dose level 4 (9 mg/m(2) per dose). Three of 14 patients received only 1 dose of GO after

  9. Aggregation of mononuclear and red blood cells through an {alpha}4{beta}1-Lu/basal cell adhesion molecule interaction in sickle cell disease. : Mononuclear and sickle red blood cell interactions

    OpenAIRE

    Chaar, Vicky; Picot, Julien; Renaud, Olivier; Bartolucci, Pablo; Nzouakou, Ruben; Bachir, Dora; Galactéros, Frédéric; Colin, Yves; Le Van Kim, Caroline; El Nemer, Wassim

    2010-01-01

    BACKGROUND: Abnormal interactions between red blood cells, leukocytes and endothelial cells play a critical role in the occurrence of the painful vaso-occlusive crises associated with sickle cell disease. We investigated the interaction between circulating leukocytes and red blood cells which could lead to aggregate formation, enhancing the incidence of vaso-occlusive crises. DESIGN AND METHODS: Blood samples from patients with sickle cell disease (n=25) and healthy subjects (n=5) were analyz...

  10. Optical chirality of protonated tetraphenylporphyrin J-aggregate formed at the liquid liquid interface in a centrifugal liquid membrane cell

    Science.gov (United States)

    Wada, Sayaka; Fujiwara, Kazuhiko; Monjushiro, Hideaki; Watarai, Hitoshi

    2007-09-01

    J-aggregation of an achiral hydrophobic porphyrin, 5,10,15,20-tetraphenylporphyrin (H2TPP), at a toluene-4 M sulfuric acid interface was studied by a centrifugal liquid membrane-circular dichroism (CLM-CD) method. It was found for the first time that the exciton chirality sign of the interfacial J-aggregate of H4TPP2+ was affected by the rotational direction of the cylindrical CLM cell: a negative sign for clockwise (CW) rotation and a positive sign for anticlockwise (ACW) rotation. The sign of the measured optical chirality also depended on the injection position of the H2TPP stock solution in the rotating cell. Furthermore, it was observed that the rotational linear velocity of the aqueous phase was faster than that of the toluene phase, when the CLM cell was rotated at 7000 rpm. The effects of rotational direction and sample injection position on the optical chirality were overcome by the effect of chiral counter-ions such as (+)- or (-)-camphorsulfonic anions. From the observed results, a possible mechanism for the generation of the optical chirality of the interfacial J-aggregate was proposed taking into account an interfacial shear force and the spreading direction of H2TPP in the toluene phase.

  11. Influence of aggregation on the performance of all-polymer solar cells containing low-bandgap naphthalenediimide copolymers

    Energy Technology Data Exchange (ETDEWEB)

    Schubert, Marcel; Roland, Steffen; Steyrleuthner, Robert; Stiller, Burkhard; Neher, Dieter [Institute of Physics and Astronomy, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476, Potsdam (Germany); Dolfen, Daniel; Scherf, Ullrich [Macromolecular Chemistry, University of Wuppertal, 42119 Wuppertal (Germany); Frisch, Johannes; Koch, Norbert [Institute of Physics, Humboldt University Berlin, Newtonstr. 15, 12489 Berlin (Germany); Chen, Zhihua; Facchetti, Antonio [Polyera Corporation, 8045 Lamon Avenue, Illinois 60077 (United States)

    2012-03-15

    The authors present efficient all-polymer solar cells comprising two different low-bandgap naphthalenediimide (NDI)-based copolymers as acceptors and regioregular P3HT as the donor. It is shown that these naphthalene copolymers have a strong tendency to preaggregate in specific organic solvents, and that preaggregation can be completely suppressed when using suitable solvents with large and highly polarizable aromatic cores. Organic solar cells prepared from such nonaggregated polymer solutions show dramatically increased power conversion efficiencies of up to 1.4%, which is mainly due to a large increase of the short circuit current. In addition, optimized solar cells show remarkable high fill factors of up to 70%. The analysis of the blend absorbance spectra reveals a surprising anticorrelation between the degree of polymer aggregation in the solid P3HT:NDI copolymer blends and their photovoltaic performance. Scanning near-field optical microscopy (SNOM) and atomic force microscopy (AFM) measurements reveal important information on the blend morphology. It is shown that films with high degree of aggregation and low photocurrents exhibit large-scale phase-separation into rather pure donor and acceptor domains. It is proposed that, by suppressing the aggregation of NDI copolymers at the early stage of film formation, the intermixing of the donor and acceptor component is improved, thereby allowing efficient harvesting of photogenerated excitons at the donor-acceptor heterojunction. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  12. JUDGMENT AGGREGATION AND PREFERENCE AGGREGATION

    OpenAIRE

    Joanna Ochremiak

    2011-01-01

    In the paper we present an introduction to the theory of judgment aggregation and discuss its relation to the theory of preference aggregation. We compare the formal model of judgment aggregation, based on logic, with the formal model of preference aggregation. Finally, we present a theorem in judgmentaggregation which is an exact analogue of Arrow's theorem for strict preferences.

  13. Pathological Propagation through Cell-to-Cell Transmission of Non-Prion Protein Aggregates in Neurodegenerative Disorders

    Science.gov (United States)

    Lee, Seung-Jae; Desplats, Paula; Sigurdson, Christina; Tsigelny, Igor; Masliah, Eliezer

    2016-01-01

    Neurodegenerative disorders such as Alzheimer's Disease, Parkinson's Disease, fronto-temporal dementia, Huntington's Disease and Creutzfeldt-Jakob Disease (CJD) are characterized by progressive accumulation of protein aggregates in selected brain regions. Protein misfolding and templated assembly into aggregates might result from an imbalance between protein synthesis, aggregation and clearance. While protein misfolding and aggregation occur in most neurodegenerative disorders, the concept of spreading and infectivity of aggregates in the CNS has been reserved to prion diseases such as CJD and bovine spongiform encephalopathy. Emerging evidence suggests that prion-like spreading may occur in other neurodegenerative disorders, taking place with secreted proteins, such as amyloid-β,) and cytosolic proteins, such as tau, huntingtin and α-synuclein. Underlying molecular mechanisms and therapeutic implications are discussed. PMID:21045796

  14. Cyclic AMP--dependent aggregation of Swiss 3T3 cells on a cellulose substratum (Cuprophan) and decreased cell membrane Rho A.

    Science.gov (United States)

    Faucheux, N; Nagel, M D

    2002-06-01

    Cell surface integrin receptors and Rho family GTPases function together to mediate adhesion-dependent events in cells. We have shown that the attachment of Swiss 3T3 cells to a cellulose substratum (Cuprophan, CU) activates adenylyl cyclase, which catalyses cyclic AMP (cAMP) production. CU adsorbs vitronectin poorly, prevents cell spreading and causes cells to aggregate. By contrast, spread cells on polystyrene (PS) contain low cAMP concentrations. We have now investigated the shift between integrin signalling-Rho A and the cAMP pathway. CU did not support the formation of focal contacts and stress fibres. The plasma membranes of cells on CU had less Rho A than those of cells on PS. Also, blocking vitronectin (VN) or fibronectin (FN)-integrin receptors with echistatin, which activates cAMP production, decreased Rho A in the plasma membrane of cells attached to PS. But adsorption of VN or FN onto CU, which limits the production of the cAMP, increased the cell membrane Rho A. Adding an inhibitor of cAMP-dependent protein kinase PKA to the medium also increased the plasma membrane Rho A in aggregated cells attached to CU. These results highlight the importance of cAMP, generated by cell attachment to substratum, as a gating element in integrin-Rho A signalling. PMID:12013176

  15. A pyrene-benzthiazolium conjugate portraying aggregation induced emission, a ratiometric detection and live cell visualization of HSO3(.).

    Science.gov (United States)

    Diwan, Uzra; Kumar, Virendra; Mishra, Rakesh K; Rana, Nishant Kumar; Koch, Biplob; Singh, Manish Kumar; Upadhyay, K K

    2016-07-27

    The present study deals with the photophysical property of a pyrene-benzthiazolium conjugate R1, as a strong intramolecular charge transfer (ICT) probe exhibiting long wavelength emission in the red region. Unlike traditional planar polyaromatic hydrocarbons whose aggregation generally quenches the light emission, the pyrene based R1 was found to display aggregation-induced emission (AIE) property along with simultaneous increase in its quantum yield upon increasing the water content of the medium. The R1 exhibits high specificity towards HSO3(-)/SO3(2-) by interrupting its own ICT producing there upon a large ratiometric blue shift of ∼220 nm in its emission spectrum. The lowest detection limit for the above measurement was found to be 8.90 × 10(-8) M. The fluorescent detection of HSO3(-) was also demonstrated excellently by test paper strip and silica coated TLC plate incorporating R1. The live cell imaging of HSO3(─) through R1 in HeLa cells was studied using fluorescence microscopic studies. The particle size and morphological features of R1 and R1-HSO3(-) aggregates in aqueous solution were characterized by DLS along with SEM analysis. PMID:27251947

  16. In vivo cell aggregations of a recent swine biofilm-forming isolate of Leptospira interrogans strain from Argentina.

    Science.gov (United States)

    Brihuega, Bibiana; Samartino, Luis; Auteri, Carmelo; Venzano, Agustín; Caimi, Karina

    2012-01-01

    Leptospirosis is a zoonosis of ubiquitous distribution caused by spirochetes. Leptospires exist either as saprophytic water-associated organisms or as animal pathogens that can survive in water. Previous works have demonstrated that both saprophytic and pathogenic leptospires are able to produce functional biofilms, which consist of a community of bacteria embedded in an extracellular matrix attached to a surface. This structure is believed to provide protection from environmental aggressiveness. In the present study, we analyzed the capacity of biofilm formation both of a a recent field isolate of Leptospira interrogans serovar Pomona obtained from an aborted swine fetus and of the saprophytic Leptospira biflexa serovar Patoc. We used light microscopy, immunofluorescence, and scanning electron microscopic examinations on glass and polystyrene plate models to evaluate the process in vitro. The ability to form bacterial aggregations in vivo was tested using pregnant guinea pigs infected with both strains. We obtained biofilms both on glass and plastic surfaces. Scanning electron microscopic analysis showed differences in the biofilm structure formed by both strains. L. interrogans serovar Pomona cell aggregations were observed in placental tissues by light microscopy. Biofilms and cell aggregations are consistent with the life of saprophytic strains in water and could help pathogenic strains to colonize the host and lead to abortion in pregnant animals. PMID:23102459

  17. The de-escalation of nuclear crises

    International Nuclear Information System (INIS)

    Whether and by what means nations can successfully de-escalate nuclear crises - and avoid the disastrous effects of nuclear war - will remain two of the most critical challenges facing humankind. Whatever the future of superpower relations, the United States, the Soviet Union, and other nations will undoubtedly continue to possess and to threaten the use of nuclear weapons. Moreover, the number of nations with nuclear weapons seems likely to increase. This examines how nations in crises might successfully move back from the brink of nuclear war - and how confidence-building measures might help and hinder the de-escalatory process

  18. De-Escalating the IT-Projects

    Directory of Open Access Journals (Sweden)

    Ghulam Muhammad Kundi

    2007-12-01

    Full Text Available Escalation stickins with an ailing project beyond rational justifications. This happens because in the face of negative feedback, decision makers are strangled between whether to stick with or quit the dying project. Environmental uncertainty has been identified as the root cause of the escalatory behavior. This uncertainty emanates from several sources relating to individual, group, organization and broader environmental factors. This paper argues the premise that effective communication can help create an environment whereby workforce can develop an organized action thereby distributing the responsibility across the whole workforce and not the individuals – leading to the possible reduction of escalatory behavior in IT projects.

  19. MRP4 knockdown enhances migration, suppresses apoptosis, and produces aggregated morphology in human retinal vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Tagami, Mizuki [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Kusuhara, Sentaro, E-mail: kusu@med.kobe-u.ac.jp [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Imai, Hisanori [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Uemura, Akiyoshi [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Department of Vascular Biology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Honda, Shigeru; Tsukahara, Yasutomo; Negi, Akira [Department of Surgery Related, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)

    2010-10-01

    Research highlights: {yields} Exogenous VEGF decreases MRP4 expression in a dose-dependent manner. {yields} MRP4 knockdown leads to enhanced cell migration. {yields} MRP4 knockdown suppresses caspase-3-mediated cell apoptosis. {yields} MRP4 knockdown produces cell assembly and cell aggregation. -- Abstract: The multidrug resistance protein (MRP) MRP4/ABCC4 is an ATP-binding cassette transporter that actively effluxes endogenous and xenobiotic substrates out of cells. In the rodent retina, Mrp4 mRNA and protein are exclusively expressed in vascular endothelial cells, but the angiogenic properties of Mrp4 are poorly understood so far. This study aims to explore the angiogenic properties of MRP4 in human retinal microvascular endothelial cells (HRECs) utilizing the RNA interference (RNAi) technique. MRP4 expression was decreased at the mRNA and protein levels after stimulation with exogenous vascular endothelial growth factor in a dose-dependent manner. RNAi-mediated MRP4 knockdown in HRECs do not affect cell proliferation but enhances cell migration. Moreover, cell apoptosis induced by serum starvation was less prominent in MRP4 siRNA-treated HRECs as compared to control siRNA-treated HRECs. In a Matrigel-based tube-formation assay, although MRP4 knockdown did not lead to a significant change in the total tube length, MRP4 siRNA-treated HRECs assembled and aggregated into a massive tube-like structure, which was not observed in control siRNA-treated HRECs. These results suggest that MRP4 is uniquely involved in retinal angiogenesis.

  20. Multidrug resistance protein 1 reduces the aggregation of mutant huntingtin in neuronal cells derived from the Huntington's disease R6/2 model.

    Science.gov (United States)

    Im, Wooseok; Ban, Jae-Jun; Chung, Jin-Young; Lee, Soon-Tae; Chu, Kon; Kim, Manho

    2015-01-01

    Mutant huntingtin (mHtt) aggregation in the nucleus is the most readily apparent phenotype and cause of neuronal death in Huntington's disease (HD). Inhibiting mHtt aggregation reduces cell death in the brain and is thus a promising therapeutic approach. The results of the present study demonstrated that mHtt aggregation in the nucleus was altered by the activity of multidrug resistance protein 1 (MDR1), which was experimentally modulated by verapamil, siRNA and an expression vector. MDR1 detoxifies drugs and metabolites through its excretory functions in the membrane compartment, thereby protecting cells against death or senescence. When they were treated with verapamil, R6/2 mice showed a progressive decline in rotarod performance and increased mHtt aggregation in the brain. Using neuronal stem cells from R6/2 mice, we developed an in vitro HD model to test mHtt accumulation in the nuclei of neurons. When MDR1 activity in cells was decreased by verapamil or siRNA, mHtt aggregation in the nuclei increased, whereas the induction of MDR1 resulted in a decrease in mHtt aggregation. Thus, our data provide evidence that MDR1 plays an important role in the clearance of mHtt aggregation and may thus be a potential target for improving the survival of neurons in Huntington's disease. PMID:26586297

  1. A computer-assisted 3D model for analyzing the aggregation of tumorigenic cells reveals specialized behaviors and unique cell types that facilitate aggregate coalescence.

    Directory of Open Access Journals (Sweden)

    Amanda Scherer

    Full Text Available We have developed a 4D computer-assisted reconstruction and motion analysis system, J3D-DIAS 4.1, and applied it to the reconstruction and motion analysis of tumorigenic cells in a 3D matrix. The system is unique in that it is fast, high-resolution, acquires optical sections using DIC microscopy (hence there is no associated photoxicity, and is capable of long-term 4D reconstruction. Specifically, a z-series at 5 μm increments can be acquired in less than a minute on tissue samples embedded in a 1.5 mm thick 3D Matrigel matrix. Reconstruction can be repeated at intervals as short as every minute and continued for 30 days or longer. Images are converted to mathematical representations from which quantitative parameters can be derived. Application of this system to cancer cells from established lines and fresh tumor tissue has revealed unique behaviors and cell types not present in non-tumorigenic lines. We report here that cells from tumorigenic lines and tumors undergo rapid coalescence in 3D, mediated by specific cell types that we have named "facilitators" and "probes." A third cell type, the "dervish", is capable of rapid movement through the gel and does not adhere to it. These cell types have never before been described. Our data suggest that tumorigenesis in vitro is a developmental process involving coalescence facilitated by specialized cells that culminates in large hollow spheres with complex architecture. The unique effects of select monoclonal antibodies on these processes demonstrate the usefulness of the model for analyzing the mechanisms of anti-cancer drugs.

  2. Molecular dissection of SO (SOFT) protein in stress-induced aggregation and cell-to-cell interactive functions in filamentous fungal multicellularity.

    Science.gov (United States)

    Tsukasaki, Wakako; Saeki, Kei; Katayama, Takuya; Maruyama, Jun-Ichi; Kitamoto, Katsuhiko

    2016-05-01

    Filamentous fungi grow by organizing multicellularity through hyphal compartmentalization and cell fusion. SO (SOFT) protein, which was originally identified in Neurospora crassa, plays distinct functional roles in cell-to-cell interactions, such as septal plugging and cell fusion. We previously reported that AoSO, an Aspergillus oryzae SO homologue, forms aggregates at the septal pore in response to stress, as well as upon hyphal wounding. However, the functional regions that mediate the multicellular functions of AoSO, which is a large protein composed of 1195 amino acids, have not been elucidated. Here, we divided AoSO protein into regions according to amino acid sequence conservation among other fungal SO homologues. By heterologous expression of full-length and truncated forms of AoSO in the yeast Saccharomyces cerevisiae, the region responsible for the stress-induced aggregation of AoSO was identified to be between amino acids 556 and 1146. In A. oryzae, however, septal localization of AoSO aggregates required the 49 C-terminal amino acids. Thus, expression of only the C-terminal half of AoSO was sufficient for septal plugging and prevention of excessive cytoplasmic loss upon hyphal wounding. In contrast, the N-terminal half of AoSO, from amino acids 1 to 555, together with the C-terminal end, was revealed to be indispensable for cell fusion. Collectively, these findings suggest that the C-terminal half of AoSO, which mediates stress-induced aggregation, is required for both septal plugging and cell fusion, whereas the N-terminal half confers an additional functionality that is essential for cell fusion. PMID:27109373

  3. Dose escalation of a curcuminoid formulation

    Directory of Open Access Journals (Sweden)

    Crowell James

    2006-03-01

    Full Text Available Abstract Background Curcumin is the major yellow pigment extracted from turmeric, a commonly-used spice in India and Southeast Asia that has broad anticarcinogenic and cancer chemopreventive potential. However, few systematic studies of curcumin's pharmacology and toxicology in humans have been performed. Methods A dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of standardized powder extract, uniformly milled curcumin (C3 Complex™, Sabinsa Corporation. Healthy volunteers were administered escalating doses from 500 to 12,000 mg. Results Seven of twenty-four subjects (30% experienced only minimal toxicity that did not appear to be dose-related. No curcumin was detected in the serum of subjects administered 500, 1,000, 2,000, 4,000, 6,000 or 8,000 mg. Low levels of curcumin were detected in two subjects administered 10,000 or 12,000 mg. Conclusion The tolerance of curcumin in high single oral doses appears to be excellent. Given that achieving systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention, these findings warrant further investigation for its utility as a long-term chemopreventive agent.

  4. Tobacco and the Escalating Global Cancer Burden

    Directory of Open Access Journals (Sweden)

    Richard F. Oppeltz

    2011-01-01

    Full Text Available The global burden of cancer is escalating as a result of dramatic increases in the use of tobacco in the developing world. The use of tobacco is linked to the development of a broad variety of cancers, mainly lung cancer, the single most common cancer in the world. Tobacco smoking-attributable deaths extends beyond cancer and include stroke, heart attack and COPD. Widening disparities in cancer-related mortality have shifted towards a more dramatic burden in the developing world. Appropriate interventions must be implemented to reduce tobacco use and prevent global mortality that has escalated to epidemic levels. Tobacco control policies, including public health advertisement campaigns, warning labels, adoption of smoke-free laws, comprehensive bans and tax policies are highly effective measures to control tobacco use. Clinicians and academic institutions have to be actively committed to support tobacco control initiatives. The reduction in cancer related morbidity and mortality should be viewed as a global crisis and definitive results will depend on a multilevel effort to effectively reduce the burden of cancer, particularly in underprivileged regions of the world.

  5. Tobacco and the escalating global cancer burden.

    Science.gov (United States)

    Oppeltz, Richard F; Jatoi, Ismail

    2011-01-01

    The global burden of cancer is escalating as a result of dramatic increases in the use of tobacco in the developing world. The use of tobacco is linked to the development of a broad variety of cancers, mainly lung cancer, the single most common cancer in the world. Tobacco smoking-attributable deaths extends beyond cancer and include stroke, heart attack and COPD. Widening disparities in cancer-related mortality have shifted towards a more dramatic burden in the developing world. Appropriate interventions must be implemented to reduce tobacco use and prevent global mortality that has escalated to epidemic levels. Tobacco control policies, including public health advertisement campaigns, warning labels, adoption of smoke-free laws, comprehensive bans and tax policies are highly effective measures to control tobacco use. Clinicians and academic institutions have to be actively committed to support tobacco control initiatives. The reduction in cancer related morbidity and mortality should be viewed as a global crisis and definitive results will depend on a multilevel effort to effectively reduce the burden of cancer, particularly in underprivileged regions of the world. PMID:21869888

  6. Air pollution control escalate equipment costs

    International Nuclear Information System (INIS)

    During fiscal year 1994, this author used the Bernard J. Steigerwald Opportunity for Independent Study, sponsored by US Environmental Protection Agency's Office of Air Quality Planning and Standards (Research Triangle Park, N.C.), to develop a group of quarterly indexes for adjusting or escalating air pollution control costs from one period to another. In all, nine indexes were developed, one equipment cost index (ECI) for each of nine control device categories. For convenience to the reader, additional indexes for two other equipment categories--available as part of the Producer Price Indexes compiled by the US Bureau of Labor Statistics--are also presented here. These 11 indexes--collectively known as the Vatavuk Air Pollution Control Cost Indexes (VAPCCI)--can be used to escalate costs from the initial (base) period (first quarter 1994) forward to any quarter in the future. To date, final indexes have been calculated (and are presented at the end of this article) for the second, third, and fourth quarters of 1994, and first quarter 1995; preliminary indexes are provided for second quarter 1995. Quarterly updates of these cost indexes will be computed as soon as the required input data become available. To date, no other set of cost indexes has been developed for such a wide array of pollution-control devices

  7. The thiG Gene Is Required for Full Virulence of Xanthomonas oryzae pv. oryzae by Preventing Cell Aggregation.

    Directory of Open Access Journals (Sweden)

    Xiaoyue Yu

    Full Text Available Bacterial blight of rice is an important serious bacterial diseases of rice in many rice-growing regions, caused by Xanthomonas oryzae pv. oryzae (Xoo. The thiG gene from Xoo strain ZJ173, which is involved with thiazole moiety production in the thiamine biosynthesis pathway, is highly conserved among the members of Xanthomonas. The thiG deletion mutant displayed impaired virulence and growth in thiamine-free medium but maintained its normal growth rate in the rice tissues, indicating that the thiG gene is involved in Xoo virulence. Compared to the wild type strain, the formation of cell-cell aggregates was affected in thiG deletion mutants. Although biofilm formation was promoted, motility and migration in rice leaves were repressed in the thiG mutants, and therefore limited the expansion of pathogen infection in rice. Quorum sensing and extracellular substance are two key factors that contribute to the formation of cell-cell aggregates. Our study found that in the thiG mutant the expression of two genes, rpfC and rpfG, which form a two-component regulatory signal system involved in the regulation of biofilm formation by a second messenger cyclic di-GMP is down-regulated. In addition, our study showed that xanthan production was not affected but the expression of some genes associated with xanthan biosynthesis, like gumD, gumE, gumH and gumM, were up-regulated in thiG mutants. Taken together, these findings are the first to demonstrate the role of the thiazole biosynthsis gene, thiG, in virulence and the formation of aggregates in Xanthomonas oryzae pv. oryzae.

  8. EDTA enhances high-throughput two-dimensional bioprinting by inhibiting salt scaling and cell aggregation at the nozzle surface.

    Science.gov (United States)

    Parzel, Cheryl A; Pepper, Matthew E; Burg, Timothy; Groff, Richard E; Burg, Karen J L

    2009-06-01

    Tissue-engineering strategies may be employed in the development of in vitro breast tissue models for use in testing regimens of drug therapies and vaccines. The physical and chemical interactions that occur among cells and extracellular matrix components can also be elucidated with these models to gain an understanding of the progression of transformed epithelial cells into tumours and the ultimate metastases of tumour cells. The modified inkjet printer may be a useful tool for creating three-dimensional (3D) in vitro models, because it offers an inexpensive and high-throughput solution to microfabrication, and because the printer can be easily manipulated to produce varying tissue attributes. We hypothesized, however, that when ink is replaced with a biologically based fluid (i.e. a 'bio-ink'), specifically a serum-free cell culture medium, printer nozzle failure can result from salt scale build-up as fluid evaporates on the printhead surface. In this study, ethylene diamine tetra-acetic acid (EDTA) was used as a culture medium additive to prevent salt scaling and cell aggregation during the bioprinting process. The results showed that EDTA, at a concentration typically found in commercially available trypsin solutions (0.53 mM), prevented nozzle failure when a serum-free culture medium was printed from a nozzle at 1000 drops/s. Furthermore, increasing concentrations of EDTA appeared to mildly decrease aggregation of 4T07 cells. Cell viability studies were performed to demonstrate that addition of EDTA did not result in significant cell death. In conclusion, it is recommended that EDTA be incorporated into bio-ink solutions containing salts that could lead to nozzle failure. PMID:19347840

  9. Simultaneous assessment of red blood cell aggregation and oxygen saturation under pulsatile flow using high-frequency photoacoustics

    Science.gov (United States)

    Bok, Tae-Hoon; Hysi, Eno; Kolios, Michael C.

    2016-01-01

    We investigate the feasibility of photoacoustic (PA) imaging for assessing the correlation between red blood cell (RBC) aggregation and the oxygen saturation (sO2) in a simulated pulsatile blood flow system. For the 750 and 850 nm illuminations, the PA amplitude (PAA) increased and decreased as the mean blood flow velocity decreased and increased, respectively, at all beat rates (60, 120 and 180 bpm). The sO2 also cyclically varied, in phase with the PAA for all beat rates. However, the linear correlation between the sO2 and the PAA at 850 nm was stronger than that at 750 nm. These results suggest that the sO2 can be correlated with RBC aggregation induced by decreased mean shear rate in pulsatile flow, and that the correlation is dependent on the optical wavelength. The hemodynamic properties of blood flow assessed by PA imaging may be used to provide a new biomarker for simultaneous monitoring blood viscosity related to RBC aggregation, oxygen delivery related to the sO2 and their clinical correlation.

  10. Simultaneous assessment of red blood cell aggregation and oxygen saturation under pulsatile flow using high-frequency photoacoustics.

    Science.gov (United States)

    Bok, Tae-Hoon; Hysi, Eno; Kolios, Michael C

    2016-07-01

    We investigate the feasibility of photoacoustic (PA) imaging for assessing the correlation between red blood cell (RBC) aggregation and the oxygen saturation (sO2) in a simulated pulsatile blood flow system. For the 750 and 850 nm illuminations, the PA amplitude (PAA) increased and decreased as the mean blood flow velocity decreased and increased, respectively, at all beat rates (60, 120 and 180 bpm). The sO2 also cyclically varied, in phase with the PAA for all beat rates. However, the linear correlation between the sO2 and the PAA at 850 nm was stronger than that at 750 nm. These results suggest that the sO2 can be correlated with RBC aggregation induced by decreased mean shear rate in pulsatile flow, and that the correlation is dependent on the optical wavelength. The hemodynamic properties of blood flow assessed by PA imaging may be used to provide a new biomarker for simultaneous monitoring blood viscosity related to RBC aggregation, oxygen delivery related to the sO2 and their clinical correlation. PMID:27446705

  11. Study of the influence of ultraviolet radiation on aggregative properties of blood red cell by light backscattering

    International Nuclear Information System (INIS)

    The method based on the fact of measurable intensity of backscattered laser beam resulting from the angular distribution of scattered light is investigated. The method permits study of the mechanisms of aggregation and disaggregation processes by ultraviolet radiation and action of some inductors. The ultraviolet light acting directly on erythrocyte rouleaus of 10 x 100 μ causes the scattering of laser beam of wavelength 632,8 nm. According the above mentioned fact at an agle of approximately 1800 the light intensity is measured. Stabilized blood sample is exposed to laser beam by means of fiber optics. Backscattering light transmitted through the photomultiplier and direct current supply is recorded. Quantitative concept of erythrocyte aggregation process is calculated from the plot. Blood sample is mixed by magnetic mixer and the measuring temperature is kept constantly at 370C. Accordingly, the present model can adequately reproduce complex blood red cells kinetics. The influence of ultraviolet radiation and different kinds of inductors on erythrocytes' aggregation is experimentally studied depending on time. 2 figs. (B.Sh.)

  12. Method for Producing Non-Neoplastic, Three Dimensional, Mammalian Tissue and Cell Aggregates Under Microgravity Culture Conditions and the Products Produced Therefrom

    Science.gov (United States)

    Goodwin, Thomas J. (Inventor); Wolf, David A. (Inventor); Spaulding, Glenn F. (Inventor); Prewett, Tracey L. (Inventor)

    1996-01-01

    Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural, and blood tissue. The cells are grown in vitro under microgravity culture conditions and form three dimensional cells aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.

  13. Aurora-A overexpression enhances cell-aggregation of Ha-ras transformants through the MEK/ERK signaling pathway

    International Nuclear Information System (INIS)

    Overexpression of Aurora-A and mutant Ras (RasV12) together has been detected in human bladder cancer tissue. However, it is not clear whether this phenomenon is a general event or not. Although crosstalk between Aurora-A and Ras signaling pathways has been reported, the role of these two genes acting together in tumorigenesis remains unclear. Real-time PCR and sequence analysis were utilized to identify Ha- and Ki-ras mutation (Gly -> Val). Immunohistochemistry staining was used to measure the level of Aurora-A expression in bladder and colon cancer specimens. To reveal the effect of overexpression of the above two genes on cellular responses, mouse NIH3T3 fibroblast derived cell lines over-expressing either RasV12and wild-type Aurora-A (designated WT) or RasV12 and kinase-inactivated Aurora-A (KD) were established. MTT and focus formation assays were conducted to measure proliferation rate and focus formation capability of the cells. Small interfering RNA, pharmacological inhibitors and dominant negative genes were used to dissect the signaling pathways involved. Overexpression of wild-type Aurora-A and mutation of RasV12 were detected in human bladder and colon cancer tissues. Wild-type Aurora-A induces focus formation and aggregation of the RasV12 transformants. Aurora-A activates Ral A and the phosphorylation of AKT as well as enhances the phosphorylation of MEK, ERK of WT cells. Finally, the Ras/MEK/ERK signaling pathway is responsible for Aurora-A induced aggregation of the RasV12 transformants. Wild-type-Aurora-A enhances focus formation and aggregation of the RasV12 transformants and the latter occurs through modulating the Ras/MEK/ERK signaling pathway

  14. Red blood cell deformability and aggregation in chronic venous disease patients with varicose veins

    OpenAIRE

    Karolina Słoczyńska; Mariusz Kózka; Henryk Marona

    2013-01-01

    Introduction: Red blood cells’ (RBC) rheological properties are disturbed in chronic venous disease (CVD). The aim of the study was to compare deformability and aggregation of erythrocytes taken from the varicose vein and the antecubital vein of patients with chronic venous disease.Materials and Methods: Blood samples were taken from twelve CVD patients presenting clinical, aetiological, anatomical and pathological elements (CEAP) stages II and III. Blood was sampled from varicose veins and a...

  15. Glycine reduces platelet aggregation

    OpenAIRE

    Schemmer, Peter; Zhong, Zhi; Galli, Uwe; Wheeler, Michael D.; Xiangli, Li; Bradford, Blair U.; Conzelmann, Lars O.; Forman, Dow; Boyer, José; Thurman, Ronald G

    2012-01-01

    It has been demonstrated that a wide variety of white blood cells and macrophages (i.e. Kupffer cells, alveolar and peritoneal macrophages and neutrophils) contain glycine-gated chloride channels. Binding of glycine on the receptor stimulates Cl− influx causing membrane hyperpolarization that prevents agonist-induced influx of calcium. Since platelet-aggregation is calcium-dependent, this study was designed to test the hypothesis that glycine would inhibit platelet aggregation. Rats were fed ...

  16. Medicinal plant extracts as anti-Escherichia coli O157:H7 agents and their effects on bacterial cell aggregation.

    Science.gov (United States)

    Voravuthikunchai, Supayang Piyawan; Limsuwan, Surasak

    2006-10-01

    Ethanolic extracts of eight Thai medicinal plants (representing five families) that are used as traditional remedies for treating diarrhea were examined with a salt aggregation test for their ability to modulate cell surface hydrophobicity of enterohemorrhagic Escherichia coli strains, including E. coli O157:H7. Four of these medicinal plants, Acacia catechu, Peltophorum pterocarpum, Punica granatum, and Quercus infectoria, have high bacteriostatic and bactericidal activities. The ethanolic extract of Q. infectoria was the most effective against all strains of E. coli, with MICs of 0.12 to 0.98 mg/ml and MBCs of 0.98 to 3.91 mg/ml. The ethanolic extract of P. granatum had MICs of 0.49 to 1.95 mg/ml and MBCs of 1.95 to 3.91 mg/ml. Ethanolic extracts of Q. infectoria, P. pterocarpum, and P. granatum were among the most effective extracts against the two strains of E. coli O157:H7. The other four plants, Andrographis paniculata, Pluchia indica, Tamarindus indica, and Walsura robusta, did not have high bacteriostatic and bactericidal activities but were able to affect hydrophobicity characteristics on their outermost surface. All plants except Q. infectoria had some ability to increase cell surface hydrophobicity. There appears to be no correlation between antibacterial activity and cell aggregative properties. PMID:17066910

  17. A platform to view huntingtin exon 1 aggregation flux in the cell reveals divergent influences from chaperones hsp40 and hsp70.

    Science.gov (United States)

    Ormsby, Angelique R; Ramdzan, Yasmin M; Mok, Yee-Foong; Jovanoski, Kristijan D; Hatters, Danny M

    2013-12-27

    Our capacity for tracking how misfolded proteins aggregate inside a cell and how different aggregation states impact cell biology remains enigmatic. To address this, we built a new toolkit that enabled the high throughput tracking of individual cells enriched with polyglutamine-expanded Htt exon 1 (Httex1) monomers, oligomers, and inclusions using biosensors of aggregation state and flow cytometry pulse shape analysis. Supplemented with gel filtration chromatography and fluorescence-adapted sedimentation velocity analysis of cell lysates, we collated a multidimensional view of Httex1 aggregation in cells with respect to time, polyglutamine length, expression levels, cell survival, and overexpression of protein quality control chaperones hsp40 (DNAJB1) and hsp70 (HSPA1A). Cell death rates trended higher for Neuro2a cells containing Httex1 in inclusions than with Httex1 dispersed through the cytosol at time points of expression over 2 days. hsp40 stabilized monomers and suppressed inclusion formation but did not otherwise change Httex1 toxicity. hsp70, however, had no major effect on aggregation of Httex1 but increased the survival rate of cells with inclusions. hsp40 and hsp70 also increased levels of a second bicistronic reporter of Httex1 expression, mKate2, and increased total numbers of cells in culture, suggesting these chaperones partly rectify Httex1-induced deficiencies in quality control and growth rates. Collectively, these data suggest that Httex1 overstretches the protein quality control resources and that the defects can be partly rescued by overexpression of hsp40 and hsp70. Importantly, these effects occurred in a pronounced manner for soluble Httex1, which points to Httex1 aggregation occurring subsequently to more acute impacts on the cell. PMID:24196953

  18. A Platform to View Huntingtin Exon 1 Aggregation Flux in the Cell Reveals Divergent Influences from Chaperones hsp40 and hsp70*

    Science.gov (United States)

    Ormsby, Angelique R.; Ramdzan, Yasmin M.; Mok, Yee-Foong; Jovanoski, Kristijan D.; Hatters, Danny M.

    2013-01-01

    Our capacity for tracking how misfolded proteins aggregate inside a cell and how different aggregation states impact cell biology remains enigmatic. To address this, we built a new toolkit that enabled the high throughput tracking of individual cells enriched with polyglutamine-expanded Htt exon 1 (Httex1) monomers, oligomers, and inclusions using biosensors of aggregation state and flow cytometry pulse shape analysis. Supplemented with gel filtration chromatography and fluorescence-adapted sedimentation velocity analysis of cell lysates, we collated a multidimensional view of Httex1 aggregation in cells with respect to time, polyglutamine length, expression levels, cell survival, and overexpression of protein quality control chaperones hsp40 (DNAJB1) and hsp70 (HSPA1A). Cell death rates trended higher for Neuro2a cells containing Httex1 in inclusions than with Httex1 dispersed through the cytosol at time points of expression over 2 days. hsp40 stabilized monomers and suppressed inclusion formation but did not otherwise change Httex1 toxicity. hsp70, however, had no major effect on aggregation of Httex1 but increased the survival rate of cells with inclusions. hsp40 and hsp70 also increased levels of a second bicistronic reporter of Httex1 expression, mKate2, and increased total numbers of cells in culture, suggesting these chaperones partly rectify Httex1-induced deficiencies in quality control and growth rates. Collectively, these data suggest that Httex1 overstretches the protein quality control resources and that the defects can be partly rescued by overexpression of hsp40 and hsp70. Importantly, these effects occurred in a pronounced manner for soluble Httex1, which points to Httex1 aggregation occurring subsequently to more acute impacts on the cell. PMID:24196953

  19. Disulfide scrambling in superoxide dismutase 1 reduces its cytotoxic effect in cultured cells and promotes protein aggregation.

    Directory of Open Access Journals (Sweden)

    Lina Leinartaitė

    Full Text Available Mutations in the gene coding for superoxide dismutase 1 (SOD1 are associated with familiar forms of the neurodegenerative disease amyotrophic lateral sclerosis (ALS. These mutations are believed to result in a "gain of toxic function", leading to neuronal degeneration. The exact mechanism is still unknown, but misfolding/aggregation events are generally acknowledged as important pathological events in this process. Recently, we observed that demetallated apoSOD1, with cysteine 6 and 111 substituted for alanine, is toxic to cultured neuroblastoma cells. This toxicity depended on an intact, high affinity Zn(2+ site. It was therefor contradictory to discover that wild-type apoSOD1 was not toxic, despite of its high affinity for Zn(2+. This inconsistency was hypothesized to originate from erroneous disulfide formation involving C6 and C111. Using high resolution non-reducing SDS-PAGE, we have in this study demonstrated that the inability of wild-type apoSOD1 to cause cell death stems from formation of non-native intra-molecular disulfides. Moreover, monomeric apoSOD1 variants capable of such disulfide scrambling aggregated into ThT positive oligomers under physiological conditions without agitation. The oligomers were stabilized by inter-molecular disulfides and morphologically resembled what has in other neurodegenerative diseases been termed protofibrils. Disulfide scrambling thus appears to be an important event for misfolding and aggregation of SOD1, but may also be significant for protein function involving cysteines, e.g. mitochondrial import and copper loading.

  20. Dissipative particle dynamics simulations of deformation and aggregation of healthy and diseased red blood cells in a tube flow

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Ting; Phan-Thien, Nhan, E-mail: Nhan@nus.edu.sg; Khoo, Boo Cheong; Lim, Chwee Teck [Department of Mechanical Engineering, National University of Singapore, Singapore 119260 (Singapore)

    2014-11-15

    In this paper, we report simulation results assessing the deformation and aggregation of mixed healthy and malaria-infected red blood cells (RBCs) in a tube flow. A three dimensional particle model based on Dissipative Particle Dynamics (DPD) is developed to predict the tube flow containing interacting cells. The cells are also modelled by DPD, with a Morse potential to characterize the cell-cell interaction. As validation tests, a single RBC in a tube flow and two RBCs in a static flow are simulated to examine the cell deformation and intercellular interaction, respectively. The study of two cells, one healthy and the other malaria-infected RBCs in a tube flow demonstrates that the malaria-infected RBC (in the leading position along flow direction) has different effects on the healthy RBC (in the trailing position) at the different stage of parasite development or at the different capillary number. With parasitic development, the malaria-infected RBC gradually loses its deformability, and in turn the corresponding trailing healthy RBC also deforms less due to the intercellular interaction. With increasing capillary number, both the healthy and malaria-infected RBCs are likely to undergo an axisymmetric motion. The minimum intercellular distance becomes small enough so that rouleaux is easily formed, i.e., the healthy and malaria-infected RBCs are difficultly disaggregated.

  1. Dissipative particle dynamics simulations of deformation and aggregation of healthy and diseased red blood cells in a tube flow

    International Nuclear Information System (INIS)

    In this paper, we report simulation results assessing the deformation and aggregation of mixed healthy and malaria-infected red blood cells (RBCs) in a tube flow. A three dimensional particle model based on Dissipative Particle Dynamics (DPD) is developed to predict the tube flow containing interacting cells. The cells are also modelled by DPD, with a Morse potential to characterize the cell-cell interaction. As validation tests, a single RBC in a tube flow and two RBCs in a static flow are simulated to examine the cell deformation and intercellular interaction, respectively. The study of two cells, one healthy and the other malaria-infected RBCs in a tube flow demonstrates that the malaria-infected RBC (in the leading position along flow direction) has different effects on the healthy RBC (in the trailing position) at the different stage of parasite development or at the different capillary number. With parasitic development, the malaria-infected RBC gradually loses its deformability, and in turn the corresponding trailing healthy RBC also deforms less due to the intercellular interaction. With increasing capillary number, both the healthy and malaria-infected RBCs are likely to undergo an axisymmetric motion. The minimum intercellular distance becomes small enough so that rouleaux is easily formed, i.e., the healthy and malaria-infected RBCs are difficultly disaggregated

  2. Effects of amphiphilic star-shaped poly(ethylene glycol) polymers with a cholic acid core on human red blood cell aggregation

    OpenAIRE

    Janvier, Florence; Julian X. X. Zhu; Armstrong, Jonathan; Meiselman, Herbert J.; Cloutier, Guy

    2012-01-01

    Elevated red blood cell (RBC) aggregation increases low-shear blood viscosity and is closely related to several pathophysiological diseases such as atherosclerosis, thrombosis, diabetes, hypertension, cancer, and hereditary chronic hemolytic conditions. Non-ionic linear polymers such as poly(ethylene glycol) (PEG) and Pluronic F68 have shown inhibitory effects against RBC aggregation. However, hypersensitivity reactions in some individuals, attributed to a diblock component of Pluronic F68, h...

  3. Rational Aggregation

    OpenAIRE

    Bruce Chapman

    2002-01-01

    In two recent papers, Christian List and Philip Pettit have argued that there is a problem in the aggregation of reasoned judgements that is akin to the aggregation of the preference problem in social choice theory.1 Indeed, List and Pettit prove a new general impossibility theorem for the aggregation of judgements, and provide a propositional interpretation of the social choice problem that suggests it is a special case of their impossibility result.2 Specifically, they show that no judgemen...

  4. A Study of Blood Flow and of Aggregation of Blood Cells Under Conditions of Zero Gravity: Its Relevance to the Occlusive Diseases and Cancer

    Science.gov (United States)

    Dintenfass, L.

    1985-01-01

    The objectives of this program are: (1) to determine whether the size of red cell aggregates, kinetics and morphology of these aggregates are influenced by near-zero gravity; (2) whether viscosity, especially at low shear rate, is afflicted by near-zero gravity (the latter preventing sedimentation of red cells); (3) whether the actual shape of red cells changes; and (4) whether blood samples obtained from different donors (normal and patients suffering from different disorders) react in the same manner to near-zero gravity.

  5. Effect of the surfactant tween 80 on the detachment and dispersal of Salmonella enterica serovar Thompson single cells and aggregates from cilantro leaves as revealed by image analysis.

    Science.gov (United States)

    Brandl, Maria T; Huynh, Steven

    2014-08-01

    Salmonella enterica has the ability to form biofilms and large aggregates on produce surfaces, including on cilantro leaves. Aggregates of S. enterica serovar Thompson that remained attached to cilantro leaves after rigorous washing and that were present free or bound to dislodged leaf tissue in the wash suspension were observed by confocal microscopy. Measurement of S. Thompson population sizes in the leaf washes by plate counts failed to show an effect of 0.05% Tween 80 on the removal of the pathogen from cilantro leaves 2 and 6 days after inoculation. On the contrary, digital image analysis of micrographs of single cells and aggregates of green fluorescent protein (GFP)-S. Thompson present in cilantro leaf washes revealed that single cells represented 13.7% of the cell assemblages in leaf washes containing Tween 80, versus 9.3% in those without the surfactant. Moreover, Tween 80 decreased the percentage of the total S. Thompson cell population located in aggregates equal to or larger than 64 cells from 9.8% to 4.4% (P < 0.05). Regression analysis of the frequency distribution of aggregate size in leaf washes with and without Tween 80 showed that the surfactant promoted the dispersal of cells from large aggregates into smaller ones and into single cells (P < 0.05). Our study underlines the importance of investigating bacterial behavior at the scale of single cells in order to uncover trends undetectable at the population level by bacterial plate counts. Such an approach may provide valuable information to devise strategies aimed at enhancing the efficacy of produce sanitization treatments. PMID:24907336

  6. In vivo venous assessment of red blood cell aggregate sizes in diabetic patients with a quantitative cellular ultrasound imaging method: proof of concept.

    Directory of Open Access Journals (Sweden)

    Julien Tripette

    Full Text Available Diabetic patients present higher level of red blood cell (RBC aggregation contributing to the development of vascular complications. While it has been suggested that this hematology/rheology parameter could bring additional prognostic information for the management of those patients, RBC aggregation screening is not included as a clinical practice. Most medical centers are not equipped to measure properly this parameter, although sedimentation tests can bring some indication. Here, we aimed at evaluating the feasibility of using ultrasound to assess in-vivo hyper-aggregation in type 2 diabetic patients.Seventeen diabetic patients and 15 control subjects underwent ultrasound measurements of RBC aggregation in both cephalic and great saphenous veins. Non-invasive in-vivo ultrasound measurements were performed using a newly developed cellular imaging technique, the structure factor size and attenuation estimator (SFSAE. Comparisons with an ex-vivo gold standard rheometry technique were done, along with measurements of pro-aggregating plasma molecule concentrations.In-vivo RBC aggregation was significantly higher in diabetic patients compared with controls for cephalic vein measurements, while a trend (p = 0.055 was noticed in the great saphenous vein. SFSAE measurements were correlated with gold standard in-vitro measures, fibrinogen and C-reactive protein plasma concentrations.RBC aggregation can be measured in-vivo in diabetic patients using ultrasound. Prospective studies are needed to determine whether the SFSAE method could help clinicians in the early management of vascular complications in this patient population.

  7. Aggregation of human platelets by endotoxic glycolipid-bearing Salmonella minnesota Re595 is prevented by synthetic peptide analogs of cell adhesion sites of fibrinogen and fibronectin

    International Nuclear Information System (INIS)

    Thrombocytopenia often accompanies sepsis due to endotoxin producing gram-negative bacteria. The authors have observed that mutant Re595 of S. minnesota induced aggregation of human platelets separated from plasma fibrinogen (Theta) and other proteins. This aggregation is dependent on ADP secreted from storage granules in response to mutant Re595. Platelet aggregation induced by mutant Re595 was prevented by simultaneously added EDTA and EGTA (5mM), whereas secretion of 14C-serotonin was maintained. Preincubation of platelets with chelators (1 hr, 370C), known to dissociate irreversibly the platelet membrane glycoprotein IIb x IIIa complex, abolished aggregation while serotonin secretion was decreased by only one fourth. Since the GPIIb x IIIa complex constitutes the receptor for Theta, its role was examined using synthetic peptide analogs of sites on gamma and alpha chains of Theta. Gamma 400-411 (225 μM) inhibited platelet aggregation induced by mutant Re595 while serotonin secretion was unaffected. Alpha 572-575 (RGDS; 100 μM), analogous to cell adhesion site of fibronectin, also prevented aggregation induced by mutant Re595. Thus, mutant Re595 causes platelet aggregation which is divalent cation-dependent and proceeds via receptor pathway for secreted adhesive macromolecules

  8. Weighted aggregation

    Science.gov (United States)

    Feiveson, A. H. (Principal Investigator)

    1979-01-01

    The use of a weighted aggregation technique to improve the precision of the overall LACIE estimate is considered. The manner in which a weighted aggregation technique is implemented given a set of weights is described. The problem of variance estimation is discussed and the question of how to obtain the weights in an operational environment is addressed.

  9. Calcium bioaccessibility and uptake by human intestinal like cells following in vitro digestion of casein phosphopeptide-calcium aggregates.

    Science.gov (United States)

    Perego, Silvia; Del Favero, Elena; De Luca, Paola; Dal Piaz, Fabrizio; Fiorilli, Amelia; Cantu', Laura; Ferraretto, Anita

    2015-06-01

    Casein phosphopeptides (CPPs), derived by casein proteolysis, can bind calcium ions and keep them in solution. In vitro studies have demonstrated CPP-induced cell calcium uptake, depending on the formation of (CPP + calcium) complexes and on the degree of differentiation of the intestinal cells. With the present study, we address the persistence of the complexes and of the CPP-induced calcium uptake in intestinal like cells after the digestion process, thus examining their eligibility to serve as nutraceuticals. A calcium-preloaded CPP preparation of commercial origin (Ca-CPPs) was subjected to in vitro digestion. The evolution of the supramolecular structure of the Ca-CPP complexes was studied using laser-light and X-ray scattering. The bioactivity of the pre- and post-digestion Ca-CPPs was determined in differentiated Caco2 and HT-29 cells by video imaging experiments using Fura-2. We found that Ca-CPP aggregates keep a complex supramolecular organization upon digestion, despite getting smaller in size and increasing internal calcium dispersion. Concomitantly and most interestingly, digested Ca-CPPs clearly enhance the uptake of calcium ions, especially in Caco2 cells. In contrast, digestion depletes the ability of post-loaded decalcified-CPPs (Ca-dekCPPs), with a weaker internal structure, to induce calcium uptake. The enhanced bioactivity reached upon digestion strongly suggests a recognized role of Ca-CPPs, in the form used here, as nutraceuticals. PMID:25927875

  10. Alginate Encapsulation Parameters Influence the Differentiation of Microencapsulated Embryonic Stem Cell Aggregates

    OpenAIRE

    Wilson, Jenna L.; Najia, Mohamad Ali; Saeed, Rabbia; McDevitt, Todd C.

    2013-01-01

    Pluripotent embryonic stem cells (ESCs) have tremendous potential as tools for regenerative medicine and drug discovery, yet the lack of processes to manufacture viable and homogenous cell populations of sufficient numbers limits the clinical translation of current and future cell therapies. Microencapsulation of ESCs within microbeads can shield cells from hydrodynamic shear forces found in bioreactor environments while allowing for sufficient diffusion of nutrients and oxygen through the en...

  11. Estimation of size of red blood cell aggregates using backscattering property of high-frequency ultrasound: In vivo evaluation

    Science.gov (United States)

    Kurokawa, Yusaku; Taki, Hirofumi; Yashiro, Satoshi; Nagasawa, Kan; Ishigaki, Yasushi; Kanai, Hiroshi

    2016-07-01

    We propose a method for assessment of the degree of red blood cell (RBC) aggregation using the backscattering property of high-frequency ultrasound. In this method, the scattering property of RBCs is extracted from the power spectrum of RBC echoes normalized by that from the posterior wall of a vein. In an experimental study using a phantom, employing the proposed method, the sizes of microspheres 5 and 20 µm in diameter were estimated to have mean values of 4.7 and 17.3 µm and standard deviations of 1.9 and 1.4 µm, respectively. In an in vivo experimental study, we compared the results between three healthy subjects and four diabetic patients. The average estimated scatterer diameters in healthy subjects at rest and during avascularization were 7 and 28 µm, respectively. In contrast, those in diabetic patients receiving both antithrombotic therapy and insulin therapy were 11 and 46 µm, respectively. These results show that the proposed method has high potential for clinical application to assess RBC aggregation, which may be related to the progress of diabetes.

  12. [Inhibition of NF-kB Activation Decreases Resistance in Acute Myeloid Leukemia Cells to TRAIL-induced Apoptosis in Multicellular Aggregates].

    Science.gov (United States)

    Fadeev, R S; Solovieva, M E; Slyadovskiy, D A; Zakharov, S G; Fadeeva, I S; Senotov, A S; Golenkov, A K; Akatov, V S

    2015-01-01

    Suppression of resistance in acute myeloid leukemia cells to TRAIL-induced apoptosis in multicellular aggregates, was studied using small molecule inhibitors of the activation of the transcription factor NF-kB - NF-k9 Activation Inhibitor IV and JSH-23 at non-toxic concentrations. NF-kB Activation Inhibitor IV and JSH-23 reduced resistance in the acute myeloid leukemia cells in multicellular aggregates to cytotoxic action of recombinant protein izTRAIL. It is shown that the use of these inhibitors decreased the phosphorylation of the RelA (p65) as a main marker activation of the transcription factor NF-kB. We discuss a possible reason for increasing resistance in acute myeloid leukemia cells to TRAIL-induced apoptosis in multicellular aggregates. PMID:26841509

  13. Pediatric multiple sclerosis: Escalation and emerging treatments.

    Science.gov (United States)

    Chitnis, Tanuja; Ghezzi, Angelo; Bajer-Kornek, Barbara; Boyko, Alexey; Giovannoni, Gavin; Pohl, Daniela

    2016-08-30

    Over the last 20 years, there have been significant advances in multiple sclerosis (MS) therapeutics, with regulatory approval for 13 therapies in adults by the European Medicines Agency (EMA) and Food and Drug Administration. However, there is only limited approval for interferon-β and glatiramer acetate use in children 12 years and older by the EMA. Availability of disease-modifying therapies to children and adolescents with MS is variable by region, and is extremely limited in some regions of the world. Up to 30% of children experience breakthrough disease requiring therapies beyond traditional first-line agents. Recent legislation in both the United States and Europe has mandated clinical studies for all new therapeutics applicable to children. Several clinical trials in children are underway that will provide important information regarding the efficacy and safety of newer drugs. This review summarizes the current knowledge of breakthrough disease, escalation, and induction treatment approaches in children with MS, especially pertaining to disease course and disability outcomes in this group of patients. In addition, ongoing clinical trials and approaches and challenges in conducting clinical trials in the pediatric population are discussed. PMID:27572854

  14. On Nuclear War: Deterrence, Escalation, and Control

    Directory of Open Access Journals (Sweden)

    Stephen J. Cimbala

    2012-12-01

    Full Text Available During the Cold War, and especially in the 1980s, there were some serious efforts in the academic and policy communities to study how a nuclear war could end. The subject of nuclear war termination should be reopened now because the threat of nuclear danger has changed from one of quantity to one of quality - who has nuclear weapons, and for what purpose are they intended? The political and technological environments relevant to starting and stopping a nuclear war since Nagasaki, neither the United States nor other great powers had though through how to abort a nuclear conflict in its early stages. This study will attempt neither to construct particular scenarios of war termination nor to examine important topics such as bargaining strategies or monitoring and verification of nuclear cease fires. The focus here is broader, namely, the political-military contexts for the management of nuclear crises and post-crisis force operations, including escalation control and war termination. Specifically, correcting the potential inability of states to terminate a nuclear war requires that military planners and policymakers first accept the concept of nuclear war termination as feasible and desirable. There are considerable obstacles standing in the way of that acceptance, not the least being the intellectual resistance by many, based on the assumption that deterrence is undermined by a willingness to plan seriously for its possible failure.

  15. Agricultural intensification escalates future conservation costs.

    Science.gov (United States)

    Phelps, Jacob; Carrasco, Luis Roman; Webb, Edward L; Koh, Lian Pin; Pascual, Unai

    2013-05-01

    The supposition that agricultural intensification results in land sparing for conservation has become central to policy formulations across the tropics. However, underlying assumptions remain uncertain and have been little explored in the context of conservation incentive schemes such as policies for Reducing Emissions from Deforestation and forest Degradation, conservation, sustainable management, and enhancement of carbon stocks (REDD+). Incipient REDD+ forest carbon policies in a number of countries propose agricultural intensification measures to replace extensive "slash-and-burn" farming systems. These may result in conservation in some contexts, but will also increase future agricultural land rents as productivity increases, creating new incentives for agricultural expansion and deforestation. While robust governance can help to ensure land sparing, we propose that conservation incentives will also have to increase over time, tracking future agricultural land rents, which might lead to runaway conservation costs. We present a conceptual framework that depicts these relationships, supported by an illustrative model of the intensification of key crops in the Democratic Republic of Congo, a leading REDD+ country. A von Thünen land rent model is combined with geographic information systems mapping to demonstrate how agricultural intensification could influence future conservation costs. Once postintensification agricultural land rents are considered, the cost of reducing forest sector emissions could significantly exceed current and projected carbon credit prices. Our analysis highlights the importance of considering escalating conservation costs from agricultural intensification when designing conservation initiatives. PMID:23589860

  16. Statistical mechanics of red blood cell aggregation: The distribution of rouleaux in thermal equilibrium

    OpenAIRE

    Wiegel, Frederik W.; Perelson, Alan S.

    1982-01-01

    When placed in suspension red blood cells adhere face-to-face and form long, cylindrical, and sometimes branched structures called rouleaux. We use methods developed in statistical mechanics to compute various statistical properties describing the size and shape of rouleaux in thermodynamic equilibrium. This leads to analytical expressions for (1) the average number of rouleaux consisting ofn cells and havingm branch points; (2) the average number of cells per rouleau; (3) the average number ...

  17. Abiotic factors in colony formation: effects of nutrition and light on extracellular polysaccharide production and cell aggregates of Microcystis aeruginosa

    Science.gov (United States)

    Yang, Zhen; Kong, Fanxiang

    2013-07-01

    Colony morphology is important for Microcystis to sustain a competitive advantage in eutrophic lakes. The mechanism of colony formation in Microcystis is currently unclear. Extracellular polysaccharide (EPS) has been reported to play an important role in cell aggregate formation of some phytoplankton. Microcystis aeruginosa was cultivated under varied abiotic conditions, including different nutrient, light, and temperature conditions, to investigate their effects on EPS production and morphological change. The results show that nutrient concentration and light intensity have great effects on EPS productionin M. aeruginosa. There was a considerable increase in EPS production after M. aeruginosa was cultivated in adjusted culture conditions similar to those present in the field (28.9 mg C/L, 1.98 mg N/L, 0.65 mg P/L, light intensity: 100 μmol/(m2 · s)). These results indicate that abiotic factors might be one of the triggers for colony formation in Microcystis.

  18. Statistical mechanics of red blood cell aggregation: The distribution of rouleaux in thermal equilibrium

    Science.gov (United States)

    Wiegel, Frederik W.; Perelson, Alan S.

    1982-12-01

    When placed in suspension red blood cells adhere face-to-face and form long, cylindrical, and sometimes branched structures called rouleaux. We use methods developed in statistical mechanics to compute various statistical properties describing the size and shape of rouleaux in thermodynamic equilibrium. This leads to analytical expressions for (1) the average number of rouleaux consisting of n cells and having m branch points; (2) the average number of cells per rouleau; (3) the average number of branch points per rouleau; and (4) the number of rouleaux with n cells in a system containing a total of N cells. We also derive asymptotic formulas that simplify these analytic expressions, and present numerical comparisons of the exact and asymptotic results.

  19. Staticial mechanics of red blood cells aggregation: The distribution of Rouleaux in thermal equilibrium

    Energy Technology Data Exchange (ETDEWEB)

    Wiegel, F.W.; Perelson, A.S.

    1982-12-01

    When placed in suspension red blood cells adhere face-to-face and form long, cylindrical, and sometimes branched structures called rouleaux. We use methods developed in statistical mechanics to compute various statistical properties describing the size and shape of rouleaux in thermodynamic equilibrium. This leads to analytical expressions for (1) the average number of rouleaux consisting of n cells and having m branch points: (2) the average number of cells per rouleau; (3) the average number of branch points per rouleau; and (4) the number of rouleaux with n cells in a system containing a total of N cells. We also derive asymptotic formulas that simplify these analytic expressions, and present numerical comparisons of the exact and asymptotic results.

  20. TTYH2, a human homologue of the Drosophila melanogaster gene tweety, is up-regulated in colon carcinoma and involved in cell proliferation and cell aggregation

    Institute of Scientific and Technical Information of China (English)

    Yuji Toiyama; Akira Mizoguchi; Kazushi Kimura; Junichirou Hiro; Yasuhiro Inoue; Tomonari Tutumi; Chikao Miki; Masato Kusunoki

    2007-01-01

    AIM: To investigate the expression patterns of TTYH2 in the human colon cancer and colon cancer cell lines and to evaluate the inhibitory effect of small interfering RNA (siRIMA) on the expression of TTYH2 in colon cancer cell lines.METHODS: We investigated the expression patterns of TTYH2 in colon cancer, adjacent non-tumorous colon mucosa, and cancer cell lines (DLD-1, caco-2, and Lovo) by RT-PCR. Furthermore, a siRNA plasmid expression vector against TTYH2 was constructed and transfected into DLD-1 and Caco-2 with LipofectamineTM 2000. The down regulation of TTYH2 expression was detected by RT-PCR and the role of siRNA in inducing cell proliferation and cell aggregation was evaluated by MTT and aggregation assay.RESULTS: TTYH2 gene expression in colon cancer tissue was significantly up-regulated compared with normal colonic mucosa (1.23 ± 0.404 vs 0.655 ± 0.373, P=0.0103). Colon cancer derived cell lines including DLD-1, Caco-2, and Lovo also expressed high levels of TTYH2. In contrast, transfection with siRNA-TTYH2 significantly inhibited both proliferation and scattering of these cancer cell lines.CONCLUSION: The present work demonstrates, for the first time, that the TTYH2 gene expression is significantly up-regulated in colon cancer. The TTYH2 gene may play an important role in regulating both proliferating and metastatic potentials of colorectal cancer.

  1. A New SDH-Based ATM Network Survivability Escalation Mechanism

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    This paper investigates survivability escalation strategies in multi-layers transport networks such as ATM/SDH/WDM networks, and presents oriented-failures and oriented-traffic escalation mechanisms. Furthermore, We present a new survivability Escalation strategy for SDH-Based ATM transport networks, which addresses difficult problem for resources sharing pool(RSP) among different layers restoration mechanisms. In this paper, we also present integer programming (IP) model for the resources sharing pool (RSP) design problem and the node simulation model for escalation Node. The simulation results show that the proposed ESP is very efficient. The proposed model can be easily extended for other types of multi-layer networks, such as WDM-based ATM networks or WDM-based SDH networks.

  2. Strategies for Biologic Image-Guided Dose Escalation: A Review

    International Nuclear Information System (INIS)

    There is increasing interest in how to incorporate functional and molecular information obtained by noninvasive, three-dimensional tumor imaging into radiotherapy. The key issues are to identify radioresistant regions that can be targeted for dose escalation, and to develop radiation dose prescription and delivery strategies providing optimal treatment for the individual patient. In the present work, we review the proposed strategies for biologic image-guided dose escalation with intensity-modulated radiation therapy. Biologic imaging modalities and the derived images are discussed, as are methods for target volume delineation. Different dose escalation strategies and techniques for treatment delivery and treatment plan evaluation are also addressed. Furthermore, we consider the need for response monitoring during treatment. We conclude with a summary of the current status of biologic image-based dose escalation and of areas where further work is needed for this strategy to become incorporated into clinical practice

  3. Individualized Tamoxifen Dose Escalation: Confirmation of Feasibility, Question of Utility.

    Science.gov (United States)

    Hertz, Daniel L; Rae, James M

    2016-07-01

    Tamoxifen may require metabolic activation to endoxifen for efficacy in treating hormone receptor-positive breast cancer. Dose escalation in patients with low endoxifen concentrations could enhance treatment efficacy. This approach is clinically feasible, and successfully increases endoxifen concentrations; however, it is unknown whether patients benefit from individualized tamoxifen dose escalation. Clin Cancer Res; 22(13); 3121-3. ©2016 AACRSee related article by Fox et al., p. 3164. PMID:27012810

  4. The fluorescent bioprobe with aggregation-induced emission features for monitoring to carbon dioxide generation rate in single living cell and early identification of cancer cells.

    Science.gov (United States)

    Chen, Didi; Wang, Huan; Dong, Lichao; Liu, Pai; Zhang, Yahui; Shi, Jianbing; Feng, Xiao; Zhi, Junge; Tong, Bin; Dong, Yuping

    2016-10-01

    A novel fluorescent probe, tris (2-(dimethylamino) ethyl)-4,4',4″-(1H-pyrrole-1,2,5-triyl) tribenzoate (TPP-TMAE), with aggregation-enhanced emission (AEE) feature showed a simple, highly selective, specific, and instant response to trace amount carbon dioxide (CO2). Because of this special characteristic, TPP-TMAE is ideal to be a biomarker for in-situ monitoring of the CO2 generation rate during the metabolism of single living cell. The rates in single living HeLa cell, MCF-7 cell, and MEF cell were 6.40 × 10(-6)±6.0 × 10(-8) μg/h, 5.78 × 10(-6)±6.0 × 10(-8) μg/h, and 4.27 × 10(-7)±4.0 × 10(-9) μg/h, respectively. The distinct responses of TPP-TMAE to CO2 generated from cancer cells and normal cells suggested TPP-TMAE as a useful tool for deeper understanding metabolism process and distinguishing cancer cells from normal cells during the early diagnosis of cancers. PMID:27372422

  5. Indole and synthetic derivative activate chaperone expression to reduce polyQ aggregation in SCA17 neuronal cell and slice culture models

    Directory of Open Access Journals (Sweden)

    Kung PJ

    2014-10-01

    Full Text Available Pin-Jui Kung,1,* Yu-Chen Tao,1,* Ho-Chiang Hsu,1 Wan-Ling Chen,1 Te-Hsien Lin,1 Donala Janreddy,2 Ching-Fa Yao,2 Kuo-Hsuan Chang,3 Jung-Yaw Lin,1 Ming-Tsan Su,1 Chung-Hsin Wu,1 Guey-Jen Lee-Chen,1 Hsiu-Mei Hsieh-Li1 1Department of Life Science, 2Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan; 3Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan *These authors contributed equally to this work Abstract: In spinocerebellar ataxia type 17 (SCA17, the expansion of a translated CAG repeat in the TATA box binding protein (TBP gene results in a long polyglutamine (polyQ tract in the TBP protein, leading to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On SH-SY5Y cells with inducible SCA17 TBP/Q79-green fluorescent protein (GFP expression to test indole and synthetic derivative NC001-8 for neuroprotection. We found that indole and NC001-8 up-regulated chaperone expression to reduce polyQ aggregation in neuronal differentiated TBP/Q79 cells. The effects on promoting neurite outgrowth and on reduction of aggregation on Purkinje cells were also confirmed with cerebellar primary and slice cultures of SCA17 transgenic mice. Our results demonstrate how indole and derivative NC001-8 reduce polyQ aggregation to support their therapeutic potentials in SCA17 treatment. Keywords: spinocerebellar ataxia type 17, TATA box binding protein, polyQ aggregation, indole and derivative, therapeutics

  6. Before the endless forms: embodied model of transition from single cells to aggregates to ecosystem engineering.

    Science.gov (United States)

    Solé, Ricard V; Valverde, Sergi

    2013-01-01

    The emergence of complex multicellular systems and their associated developmental programs is one of the major problems of evolutionary biology. The advantages of cooperation over individuality seem well known but it is not clear yet how such increase of complexity emerged from unicellular life forms. Current multicellular systems display a complex cell-cell communication machinery, often tied to large-scale controls of body size or tissue homeostasis. Some unicellular life forms are simpler and involve groups of cells cooperating in a tissue-like fashion, as it occurs with biofilms. However, before true gene regulatory interactions were widespread and allowed for controlled changes in cell phenotypes, simple cellular colonies displaying adhesion and interacting with their environments were in place. In this context, models often ignore the physical embedding of evolving cells, thus leaving aside a key component. The potential for evolving pre-developmental patterns is a relevant issue: how far a colony of evolving cells can go? Here we study these pre-conditions for morphogenesis by using CHIMERA, a physically embodied computational model of evolving virtual organisms in a pre-Mendelian world. Starting from a population of identical, independent cells moving in a fluid, the system undergoes a series of changes, from spatial segregation, increased adhesion and the development of generalism. Eventually, a major transition occurs where a change in the flow of nutrients is triggered by a sub-population. This ecosystem engineering phenomenon leads to a subsequent separation of the ecological network into two well defined compartments. The relevance of these results for evodevo and its potential ecological triggers is discussed. PMID:23596506

  7. Aggregate productivity and aggregate technology

    OpenAIRE

    Susanto Basu; John G. Fernald

    1997-01-01

    Aggregate productivity and aggregate technology are meaningful but distinct concepts. We show that a slightly-modified Solow productivity residual measures changes in economic welfare, even when productivity and technology differ because of distortions such as imperfect competition. We then present a general accounting framework that identifies several new non-technological gaps between productivity and technology, gaps reflecting imperfections and frictions in output and factor markets. Empi...

  8. Erythrocyte aggregation in flowing blood

    International Nuclear Information System (INIS)

    This paper addresses the issue of whether nonionic contrast media (CM) promote thrombosis by the formation of large, irregular red blood cell aggregates with videomicroscopy and a flow chamber, red blood cell aggregates adjacent to an endothelial cell monolayer were imaged at 17 sec-1 in dilute suspensions (hematocrit, --8) at 370C in plasma with 20% CM by non-red blood cell volume. All aggregates were rouleaux (<100 μm) readily dispersed at higher shear rates. Aggregate length in eight experiments was increased 11% by ioxaglate (320 mg of iodine per milliliter), decreased 58% by diatrizoate (370 mg of iodine per milliliter) but reduced similarly (16%) by iohexol (350 mg of iodine per milliliter) and saline. Iohexol did not enhance platelet aggregation on injured monolayers

  9. Submicron-Scale Heterogeneities in Nickel Sorption of Various Cell-Mineral Aggregates Formed by Fe(II)-Oxidizing Bacteria.

    Science.gov (United States)

    Schmid, Gregor; Zeitvogel, Fabian; Hao, Likai; Ingino, Pablo; Adaktylou, Irini; Eickhoff, Merle; Obst, Martin

    2016-01-01

    Fe(II)-oxidizing bacteria form biogenic cell-mineral aggregates (CMAs) composed of microbial cells, extracellular organic compounds, and ferric iron minerals. CMAs are capable of immobilizing large quantities of heavy metals, such as nickel, via sorption processes. CMAs play an important role for the fate of heavy metals in the environment, particularly in systems characterized by elevated concentrations of dissolved metals, such as mine drainage or contaminated sediments. We applied scanning transmission (soft) X-ray microscopy (STXM) spectrotomography for detailed 3D chemical mapping of nickel sorbed to CMAs on the submicron scale. We analyzed different CMAs produced by phototrophic or nitrate-reducing microbial Fe(II) oxidation and, in addition, a twisted stalk structure obtained from an environmental biofilm. Nickel showed a heterogeneous distribution and was found to be preferentially sorbed to biogenically precipitated iron minerals such as Fe(III)-(oxyhydr)oxides and, to a minor extent, associated with organic compounds. Some distinct nickel accumulations were identified on the surfaces of CMAs. Additional information obtained from scatter plots and angular distance maps, showing variations in the nickel-iron and nickel-organic carbon ratios, also revealed a general correlation between nickel and iron. Although a high correlation between nickel and iron was observed in 2D maps, 3D maps revealed this to be partly due to projection artifacts. In summary, by combining different approaches for data analysis, we unambiguously showed the heterogeneous sorption behavior of nickel to CMAs. PMID:26588096

  10. Erythrocyte aggregation: Basic aspects and clinical importance

    OpenAIRE

    Başkurt, Oğuz K.; Meiselman, Herbert J.

    2013-01-01

    Red blood cells (RBC) aggregate to form two- and three-dimensional structures when suspended in aqueous solutions containing large plasma proteins or polymers; this aggregation is reversible and shear dependent (i.e., dispersed at high shear and reformed at low or stasis). The extent of aggregation is the main determinant of low shear blood viscosity, thus predicting an inverse relationship between aggregation and in vivo blood flow. However, the effects of aggregation on hemodynamic mechanis...

  11. The Role of Molecular Quantum Electrodynamics in Linear Aggregations of Red Blood Cells

    OpenAIRE

    Bradonjic, K.; Swain, J. D.; Widom, A.; Srivastava, Y. N.

    2004-01-01

    Despite the fact that red blood cells carry negative charges, under certain conditions they form cylindrical stacks, or ``rouleaux''. It is shown here that a form of the Casimir effect, generalizing the more well-known van der Waals forces, can provide the necessary attractive force to balance the electrostatic repulsion. Erythrocytes in plasma are modelled as negatively charged dielectric disks in an ionic solution, allowing predictions to be made about the conditions under which rouleaux wi...

  12. Aqueous chemical synthesis of large-scale ZnO aggregates with high-efficient light-scattering and application in dye-sensitized solar cells

    International Nuclear Information System (INIS)

    Highlights: ► An aqueous chemical method for preparing polydispersed ZnO aggregates is presented. ► TEA concentration is crucial to morphology and performance of ZnO electrode films. ► Efficiencies of 3.91% and 2.22% for rigid and flexible devices, respectively. ► Application of ZnO aggregates in the flexible photoanode for the first time. -- Abstract: We report on the synthesis of polydisperse ZnO aggregates with large average diameter of 700 ± 150 nm comparable to the wavelengths of the visible region, and their implementation in both rigid and flexible photoanodes of dye-sensitized solar cells (DSCs). The ZnO aggregates were prepared through an aqueous chemical method in triethanolamine (TEA)-based aqueous system, followed by the characterizations of scanning electron microscopy (SEM), X-ray diffraction (XRD) and diffuse reflectance spectra (DRS). It was found that the size of as-prepared ZnO aggregates could be experimentally controlled by varying TEA concentrations initially added. With a TEA concentration of 25%, ∼700 nm-sized ZnO aggregates based film exhibited the highest reflectance of 75–90% in the visible wavelength region. The photoelectrical efficiencies of the corresponding cells based on rigid and flexible photoanodes were achieved maximum up to be 3.91% and 2.22% under 100 mW cm−2 AM 1.5 illumination, respectively. The excellent performance was mainly due to the more efficient light-harvest of the electrode film indicated by the incident photon-to-current efficiency (IPCE) and lower charge transfer resistance at the ZnO/dye/electrolyte interface evidenced by electrochemical impedance spectroscopy (EIS)

  13. Cytoplasmic location of α1A voltage-gated calcium channel C-terminal fragment (Cav2.1-CTF) aggregate is sufficient to cause cell death.

    Science.gov (United States)

    Takahashi, Makoto; Obayashi, Masato; Ishiguro, Taro; Sato, Nozomu; Niimi, Yusuke; Ozaki, Kokoro; Mogushi, Kaoru; Mahmut, Yasen; Tanaka, Hiroshi; Tsuruta, Fuminori; Dolmetsch, Ricardo; Yamada, Mitsunori; Takahashi, Hitoshi; Kato, Takeo; Mori, Osamu; Eishi, Yoshinobu; Mizusawa, Hidehiro; Ishikawa, Kinya

    2013-01-01

    The human α1A voltage-dependent calcium channel (Cav2.1) is a pore-forming essential subunit embedded in the plasma membrane. Its cytoplasmic carboxyl(C)-tail contains a small poly-glutamine (Q) tract, whose length is normally 4∼19 Q, but when expanded up to 20∼33Q, the tract causes an autosomal-dominant neurodegenerative disorder, spinocerebellar ataxia type 6 (SCA6). A recent study has shown that a 75-kDa C-terminal fragment (CTF) containing the polyQ tract remains soluble in normal brains, but becomes insoluble mainly in the cytoplasm with additional localization to the nuclei of human SCA6 Purkinje cells. However, the mechanism by which the CTF aggregation leads to neurodegeneration is completely elusive, particularly whether the CTF exerts more toxicity in the nucleus or in the cytoplasm. We tagged recombinant (r)CTF with either nuclear-localization or nuclear-export signal, created doxycyclin-inducible rat pheochromocytoma (PC12) cell lines, and found that the CTF is more toxic in the cytoplasm than in the nucleus, the observations being more obvious with Q28 (disease range) than with Q13 (normal-length). Surprisingly, the CTF aggregates co-localized both with cAMP response element-binding protein (CREB) and phosphorylated-CREB (p-CREB) in the cytoplasm, and Western blot analysis showed that the quantity of CREB and p-CREB were both decreased in the nucleus when the rCTF formed aggregates in the cytoplasm. In human brains, polyQ aggregates also co-localized with CREB in the cytoplasm of SCA6 Purkinje cells, but not in other conditions. Collectively, the cytoplasmic Cav2.1-CTF aggregates are sufficient to cause cell death, and one of the pathogenic mechanisms may be abnormal CREB trafficking in the cytoplasm and reduced CREB and p-CREB levels in the nuclei. PMID:23505410

  14. Cytoplasmic location of α1A voltage-gated calcium channel C-terminal fragment (Cav2.1-CTF aggregate is sufficient to cause cell death.

    Directory of Open Access Journals (Sweden)

    Makoto Takahashi

    Full Text Available The human α1A voltage-dependent calcium channel (Cav2.1 is a pore-forming essential subunit embedded in the plasma membrane. Its cytoplasmic carboxyl(C-tail contains a small poly-glutamine (Q tract, whose length is normally 4∼19 Q, but when expanded up to 20∼33Q, the tract causes an autosomal-dominant neurodegenerative disorder, spinocerebellar ataxia type 6 (SCA6. A recent study has shown that a 75-kDa C-terminal fragment (CTF containing the polyQ tract remains soluble in normal brains, but becomes insoluble mainly in the cytoplasm with additional localization to the nuclei of human SCA6 Purkinje cells. However, the mechanism by which the CTF aggregation leads to neurodegeneration is completely elusive, particularly whether the CTF exerts more toxicity in the nucleus or in the cytoplasm. We tagged recombinant (rCTF with either nuclear-localization or nuclear-export signal, created doxycyclin-inducible rat pheochromocytoma (PC12 cell lines, and found that the CTF is more toxic in the cytoplasm than in the nucleus, the observations being more obvious with Q28 (disease range than with Q13 (normal-length. Surprisingly, the CTF aggregates co-localized both with cAMP response element-binding protein (CREB and phosphorylated-CREB (p-CREB in the cytoplasm, and Western blot analysis showed that the quantity of CREB and p-CREB were both decreased in the nucleus when the rCTF formed aggregates in the cytoplasm. In human brains, polyQ aggregates also co-localized with CREB in the cytoplasm of SCA6 Purkinje cells, but not in other conditions. Collectively, the cytoplasmic Cav2.1-CTF aggregates are sufficient to cause cell death, and one of the pathogenic mechanisms may be abnormal CREB trafficking in the cytoplasm and reduced CREB and p-CREB levels in the nuclei.

  15. Improvement in tumour control probability with active breathing control and dose escalation: A modelling study

    International Nuclear Information System (INIS)

    Introduction: The prognosis from non-small cell lung cancer remains poor, even in those patients suitable for radical radiotherapy. The ability of radiotherapy to achieve local control is hampered by the sensitivity of normal structures to irradiation at the high tumour doses needed. This study aimed to look at the potential gain in tumour control probability from dose escalation facilitated by moderate deep inspiration breath-hold. Method: The data from 28 patients, recruited into two separate studies were used. These patients underwent planning with and without the use of moderate deep inspiration breath-hold with an active breathing control (ABC) device. Whilst maintaining the mean lung dose (MLD) at the level of the conventional plan, the ABC plan dose was theoretically escalated to a maximum of 84 Gy, constrained by usual normal tissue tolerances. Calculations were performed using data for both lungs and for the ipsilateral lung only. Resulting local progression-free survival at 30 months was calculated using a standard logistic model. Results: The prescription dose could be escalated from 64 Gy to a mean of 73.7 ± 6.5 Gy without margin reduction, which represents a statistically significant increase in tumour control probability from 0.15 ± 0.01 to 0.29 ± 0.11 (p < 0.0001). The results were not statistically different whether both lungs or just the ipsilateral lung was used for calculations. Conclusion: A near-doubling of tumour control probability is possible with modest dose escalation, which can be achieved with no extra increase in lung dose if deep inspiration breath-hold techniques are used.

  16. Abiotic factors in colony formation: effects of nutrition and light on extracellular polysaccharide production and cell aggregates of Microcystis aeruginosa

    Institute of Scientific and Technical Information of China (English)

    YANG Zhen; KONG Fanxiang

    2013-01-01

    Colony morphology is important for Microcystis to sustain a competitive advantage in eutrophic lakes.The mechanism of colony formation in Microcystis is currently unclear.Extracellular polysaccharide (EPS) has been reported to play an important role in cell aggregate formation of some phytoplankton.Microcystis aeruginosa was cultivated under varied abiotic conditions,including different nutrient,light,and temperature conditions,to investigate their effects on EPS production and morphological change.The results show that nutrient concentration and light intensity have great effects on EPS production in M.aeruginosa.There was a considerable increase in EPS production after M.aeruginosa was cultivated in adjusted culture conditions similar to those present in the field (28.9 mg C/L,1.98 mg N/L,0.65 mg P/L,light intensity:100 μmol/(m2·s)).These results indicate that abiotic factors might be one of the triggers for colony formation in Microcystis.

  17. Interplay Between Side Chain Pattern, Polymer Aggregation, and Charge Carrier Dynamics in PBDTTPD:PCBM Bulk-Heterojunction Solar Cells

    KAUST Repository

    Dyer-Smith, Clare

    2015-05-01

    Poly(benzo[1,2-b:4,5-b′]dithiophene–alt–thieno[3,4-c]pyrrole-4,6-dione) (PBDTTPD) polymer donors with linear side-chains yield bulk-heterojunction (BHJ) solar cell power conversion efficiencies (PCEs) of about 4% with phenyl-C71-butyric acid methyl ester (PC71BM) as the acceptor, while a PBDTTPD polymer with a combination of branched and linear substituents yields a doubling of the PCE to 8%. Using transient optical spectroscopy it is shown that while the exciton dissociation and ultrafast charge generation steps are not strongly affected by the side chain modifications, the polymer with branched side chains exhibits a decreased rate of nongeminate recombination and a lower fraction of sub-nanosecond geminate recombination. In turn the yield of long-lived charge carriers increases, resulting in a 33% increase in short circuit current (J sc). In parallel, the two polymers show distinct grazing incidence X-ray scattering spectra indicative of the presence of stacks with different orientation patterns in optimized thin-film BHJ devices. Independent of the packing pattern the spectroscopic data also reveals the existence of polymer aggregates in the pristine polymer films as well as in both blends which trap excitons and hinder their dissociation.

  18. Pancreatic Islet-Like Three-Dimensional Aggregates Derived From Human Embryonic Stem Cells Ameliorate Hyperglycemia in Streptozotocin-Induced Diabetic Mice.

    Science.gov (United States)

    Shim, Joong-Hyun; Kim, JongHyun; Han, Jiyou; An, Su Yeon; Jang, Yu Jin; Son, Jeongsang; Woo, Dong-Hun; Kim, Suel-Kee; Kim, Jong-Hoon

    2015-01-01

    We previously reported the in vitro differentiation of human embryonic stem cells (hESCs) into pancreatic endoderm. Here we demonstrate that islet-like three-dimensional (3D) aggregates can be derived from the pancreatic endoderm by optimizing our previous protocol. Sequential treatment with Wnt3a, activin A, and noggin induced a transient upregulation of T and MixL1, followed by increased expression of endodermal genes, including FOXA2, SOX17, and CXCR4. Subsequent treatment with retinoic acid highly upregulated PDX1 expression. We also show that inhibition of sonic hedgehog signaling by bFGF/activin βB and cotreatment with VEGF and FGF7 produced many 3D cellular clusters that express both SOX17 and PDX1. We found for the first time that proteoglycans and vimentin(+) mesenchymal cells were mainly localized in hESC-derived PDX1(+) clusters. Importantly, treatment with chlorate, an inhibitor of proteoglycan sulfation, together with inhibition of Notch signaling significantly increased the expression of Neurog3 and NeuroD1, promoting a transition from PDX1(+) progenitor cells toward mature pancreatic endocrine cells. Purified dithizone(+) 3D aggregates generated by our refined protocol produced pancreatic hormones and released insulin in response to both glucose and pharmacological drugs in vitro. Furthermore, the islet-like 3D aggregates decreased blood glucose levels and continued to exhibit pancreatic features after transplantation into diabetic mice. Generation of islet-like 3D cell aggregates from human pluripotent stem cells may overcome the shortage of cadaveric donor islets for future cases of clinical islet transplantation. PMID:25397866

  19. Three-dimensional printed polymeric system to encapsulate human mesenchymal stem cells differentiated into islet-like insulin-producing aggregates for diabetes treatment

    Science.gov (United States)

    Sabek, Omaima M; Farina, Marco; Fraga, Daniel W; Afshar, Solmaz; Ballerini, Andrea; Filgueira, Carly S; Thekkedath, Usha R; Grattoni, Alessandro; Gaber, A Osama

    2016-01-01

    Diabetes is one of the most prevalent, costly, and debilitating diseases in the world. Pancreas and islet transplants have shown success in re-establishing glucose control and reversing diabetic complications. However, both are limited by donor availability, need for continuous immunosuppression, loss of transplanted tissue due to dispersion, and lack of vascularization. To overcome the limitations of poor islet availability, here, we investigate the potential of bone marrow–derived mesenchymal stem cells differentiated into islet-like insulin-producing aggregates. Islet-like insulin-producing aggregates, characterized by gene expression, are shown to be similar to pancreatic islets and display positive immunostaining for insulin and glucagon. To address the limits of current encapsulation systems, we developed a novel three-dimensional printed, scalable, and potentially refillable polymeric construct (nanogland) to support islet-like insulin-producing aggregates’ survival and function in the host body. In vitro studies showed that encapsulated islet-like insulin-producing aggregates maintained viability and function, producing steady levels of insulin for at least 4 weeks. Nanogland—islet-like insulin-producing aggregate technology here investigated as a proof of concept holds potential as an effective and innovative approach for diabetes cell therapy. PMID:27152147

  20. The Role of the Midmolecular Peptides in the Blood Cell Aggregation in Acute Periods of a Burn Disease

    Directory of Open Access Journals (Sweden)

    Egorikhina M.N.

    2011-03-01

    Full Text Available The aim of the investigation is to study the effect of midmolecular peptide (MMP concentration on platelet and erythrocyte aggregation in severe burned patients. Materials and Methods. The investigation was carried out on 34 blood samples of healthy people and 30 blood samples of severe burned patients. There was determined the level of MMP, as well as that of creatinine, and urea. The “Amicon Ultra-4” microcentrifuge tubes were used to isolate MMP. Results. The level increase of average mass molecules isolated from the blood plasma of patients in an acute period of a burn disease has been stated to cause a progressive increase of platelet aggregation of healthy donors. The erythrocyte aggregation increase in such conditions is observed only in very high MMP concentrations. Creatinine and urea do not practically effect the ADP-induced platelet aggregation and the erythrocyte aggregation of healthy donors, and even decrease spontaneous thrombocyte aggregation in very high concentrations occur in an acute renal insufficiency. Conclusion. One of the reasons of platelet aggregation decrease under the influence of chemosorption in a burn disease can be the decrease of the MMP concentration in response to chemosorption.

  1. Non-aggregated Zn(ii)octa(2,6-diphenylphenoxy) phthalocyanine as a hole transporting material for efficient perovskite solar cells

    OpenAIRE

    Ramos, F. Javier; Ince, M.; Urbani, M.; Abate, Antonio; Grätzel, M.; Ahmad, Shahzada; Torres, T.; Nazeeruddin, Mohammad Khaja

    2015-01-01

    A non-aggregated Zn(ii)octa(2,6-diphenylphenoxy) phthalocyanine (coded as TT80) has been used as a hole-transporting material for perovskite solar cells. The cells were fabricated under three different configurations by changing the uptake solvent (chlorobenzene or toluene) and incorporating additives (bis(trifluoromethane) sulfonimide lithium salt (LiTFSI) and 4-tert-butylpyridine (TBP). A power conversion efficiency of 6.7% (AM1.5G standard conditions) was achieved for the best cell under o...

  2. Phase I dose escalation, pharmacokinetic and pharmacodynamic study of naptumomab estafenatox alone in patients with advanced cancer and with docetaxel in patients with advanced non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Borghaei, Hossein; Alpaugh, Katherine; Hedlund, Gunnar;

    2009-01-01

    COMBO study, the MTD was 22 microg/kg (neutropenic sepsis). Adverse events included grade 1 to 2 fever, hypotension, nausea, and chills. Treatment caused a systemic increase of inflammatory cytokines and selective expansion of SEA/E-120 reactive T-cells. Tumor biopsies demonstrated T-cell infiltration......: Thirty-nine patients were enrolled in the MONO study and 13 were enrolled in the COMBO study. The monotherapy MTD was 26 microg/kg (NSCLC and PC) and 15 microg/kg (RCC). Dose-limiting toxicities (DLTs) in the MONO study were fever, hypotension, acute liver toxicity, and vascular leak syndrome. In the...

  3. [Lysophosphatidic acid and human erythrocyte aggregation].

    Science.gov (United States)

    Sheremet'ev, Iu A; Popovicheva, A N; Levin, G Ia

    2014-01-01

    The effects of lysophosphatidic acid on the morphology and aggregation of human erythrocytes has been studied. Morphology of erythrocytes and their aggregates were studied by light microscopy. It has been shown that lysophosphatidic acid changes the shape of red blood cells: diskocyte become echinocytes. Aggregation of red blood cells (rouleaux) was significantly reduced in autoplasma. At the same time there is a strong aggregation of echinocytes. This was accompanied by the formation of microvesicles. Adding normal plasma to echinocytes restores shape and aggregation of red blood cells consisting of "rouleaux". A possible mechanism of action of lysophosphatidic acid on erythrocytes is discussed. PMID:25509147

  4. Aggregation of tetraspanin CD9 causes activation of mast cells and inhibits their chemotaxis toward antigen and stem cell factor

    Czech Academy of Sciences Publication Activity Database

    Hálová, Ivana

    Nijmegen, 2012. [5th European Conference on Tetraspanins. Nijmegen (NL), 26.09.2012-28.09.2012] R&D Projects: GA ČR GA301/09/1826; GA ČR GAP302/10/1759; GA ČR(CZ) GBP302/12/G101 Institutional support: RVO:68378050 Keywords : tetraspanin * mast cells * CD9 Subject RIV: EB - Genetics ; Molecular Biology

  5. 29 CFR 1917.116 - Elevators and escalators.

    Science.gov (United States)

    2010-07-01

    ... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... landing, to prevent employees from falling into the shaft. (g) The elevator's or escalator's maximum load limits shall be posted and not exceeded. Elevator load limits shall be posted conspicuously both...

  6. Elevator and Escalator Safety Education for Older Adults.

    Science.gov (United States)

    Hanks, Roma Stovall

    1996-01-01

    In eight focus groups in five cities, older adults identified their concerns about safety on elevators and escalators, often related to misunderstanding of the equipment. Their preferences for delivery of safety information included video/television, pamphlets, discussions, and posters. Educational interventions and modifications for disabilities…

  7. Simulation and analysis of individual trampling risk during escalator transfers

    Science.gov (United States)

    Li, Wenhang; Gong, Jianhua; Yu, Ping; Shen, Shen; Li, Rong; Duan, Qishen

    2014-08-01

    A type of trampling process that is caused by picking-up activities during escalator transfers was studied in this paper. A five-stage trampling model for individual pedestrians was proposed, and the social force model was modified considering the transfer features. Several scenarios were simulated to study the impacts of 4 factors, namely, pedestrian traffic, escalator velocity, picking-up duration and pedestrian velocity, on trampling probability. The results show that pedestrian traffic strongly affects the trampling probability, with a positive correlation throughout all scenarios; the picking-up duration affects the trampling probability, with a negative correlation throughout all scenarios; lower pedestrian velocities can result in higher trampling probabilities if the picking-up duration is short; and the escalator velocity may also affect the trampling probability, but there are no general rules for all scenarios. Thus, the impacts of these 4 factors can be queued in descending order as follows: pedestrian traffic > picking-up duration > pedestrian velocity > escalator velocity. Countermeasures can be employed according to the results to reduce trampling risks.

  8. The influence of fast neutron irradiation through micropropagation, calli induction and cell aggregate suspension culture of tapak dara cultivate vinca rosea linn

    International Nuclear Information System (INIS)

    Study on the influence of fast neutron irradiation toward tissue induction of apical shoot, calli of leaf and corolla as well as development of bud micropropagation using variety of MS and Gamborg (B5) which were supplemented with growth hormone 2,4-D NAA, BAP and kinetin has been carried out. Cell aggregates were obtained from modified liquid media by mixing MS macro element and Gamborg vitamin. Influence of the iow level irradiation (0,5-10 Gy) was investigated for auxiliary bud micropropagation , middle (5 - 20 Gy) for calli induction, while for call aggregates higher doses (until 30 Gy) were used. Optimum growth of bud micropropagation was stimulate at dose range between 0,5-1Gy and grown on MS supplemented whit BAP and NAAN, while for leaf and corolla calli was at 5 Gy, on MS media which was supplemented whit 1 mg/L kinetin, 10mg/L BAP and 0,5 mg/L NAA. However, neutron dose of 10 Gy decreased the induction of leaf and corolla calli. The highest radioresistance was shown by cell aggregates of leaf calli that grew prosperously up to 20Gy. Key words : fast neutron, micropropagation, tissue culture, cell culture, vinca rosea L

  9. Optical chirality of protonated tetraphenylporphyrin J-aggregate formed at the liquid-liquid interface in a centrifugal liquid membrane cell

    International Nuclear Information System (INIS)

    J-aggregation of an achiral hydrophobic porphyrin, 5,10,15,20-tetraphenylporphyrin (H2TPP), at a toluene-4 M sulfuric acid interface was studied by a centrifugal liquid membrane-circular dichroism (CLM-CD) method. It was found for the first time that the exciton chirality sign of the interfacial J-aggregate of H4TPP2+ was affected by the rotational direction of the cylindrical CLM cell: a negative sign for clockwise (CW) rotation and a positive sign for anticlockwise (ACW) rotation. The sign of the measured optical chirality also depended on the injection position of the H2TPP stock solution in the rotating cell. Furthermore, it was observed that the rotational linear velocity of the aqueous phase was faster than that of the toluene phase, when the CLM cell was rotated at 7000 rpm. The effects of rotational direction and sample injection position on the optical chirality were overcome by the effect of chiral counter-ions such as (+)- or (-)-camphorsulfonic anions. From the observed results, a possible mechanism for the generation of the optical chirality of the interfacial J-aggregate was proposed taking into account an interfacial shear force and the spreading direction of H2TPP in the toluene phase

  10. Arginine-glycine-aspartic acid-polyethylene glycol-polyamidoamine dendrimer conjugate improves liver-cell aggregation and function in 3-D spheroid culture.

    Science.gov (United States)

    Chen, Zhanfei; Lian, Fen; Wang, Xiaoqian; Chen, Yanling; Tang, Nanhong

    2016-01-01

    The polyamidoamine (PAMAM) dendrimer, a type of macromolecule material, has been used in spheroidal cell culture and drug delivery in recent years. However, PAMAM is not involved in the study of hepatic cell-spheroid culture or its biological activity, particularly in detoxification function. Here, we constructed a PAMAM-dendrimer conjugate decorated by an integrin ligand: arginine-glycine-aspartic acid (RGD) peptide. Our studies demonstrate that RGD-polyethylene glycol (PEG)-PAMAM conjugates can promote singly floating hepatic cells to aggregate together in a sphere-like growth with a weak reactive oxygen species. Moreover, RGD-PEG-PAMAM conjugates can activate the AKT-MAPK pathway in hepatic cells to promote cell proliferation and improve basic function and ammonia metabolism. Together, our data support the hepatocyte sphere treated by RGD-PEG-PAMAM conjugates as a potential source of hepatic cells for a biological artificial liver system. PMID:27621619

  11. Reinjury risk of nano-calcium oxalate monohydrate and calcium oxalate dihydrate crystals on injured renal epithelial cells: aggravation of crystal adhesion and aggregation

    Science.gov (United States)

    Gan, Qiong-Zhi; Sun, Xin-Yuan; Bhadja, Poonam; Yao, Xiu-Qiong; Ouyang, Jian-Ming

    2016-01-01

    Background Renal epithelial cell injury facilitates crystal adhesion to cell surface and serves as a key step in renal stone formation. However, the effects of cell injury on the adhesion of nano-calcium oxalate crystals and the nano-crystal-induced reinjury risk of injured cells remain unclear. Methods African green monkey renal epithelial (Vero) cells were injured with H2O2 to establish a cell injury model. Cell viability, superoxide dismutase (SOD) activity, malonaldehyde (MDA) content, propidium iodide staining, hematoxylin–eosin staining, reactive oxygen species production, and mitochondrial membrane potential (Δψm) were determined to examine cell injury during adhesion. Changes in the surface structure of H2O2-injured cells were assessed through atomic force microscopy. The altered expression of hyaluronan during adhesion was examined through laser scanning confocal microscopy. The adhesion of nano-calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) crystals to Vero cells was observed through scanning electron microscopy. Nano-COM and COD binding was quantitatively determined through inductively coupled plasma emission spectrometry. Results The expression of hyaluronan on the cell surface was increased during wound healing because of Vero cell injury. The structure and function of the cell membrane were also altered by cell injury; thus, nano-crystal adhesion occurred. The ability of nano-COM to adhere to the injured Vero cells was higher than that of nano-COD crystals. The cell viability, SOD activity, and Δψm decreased when nano-crystals attached to the cell surface. By contrast, the MDA content, reactive oxygen species production, and cell death rate increased. Conclusion Cell injury contributes to crystal adhesion to Vero cell surface. The attached nano-COM and COD crystals can aggravate Vero cell injury. As a consequence, crystal adhesion and aggregation are enhanced. These findings provide further insights into kidney stone

  12. Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy

    International Nuclear Information System (INIS)

    It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1aggregation, the amount of circulating endothelial and platelet microparticles, or endothelial progenitor cells. Cardiovascular protection following therapy with simvastatin/ezetimibe seems restricted to lipid changes and improvement of endothelial function not affecting the release of microparticles, mobilization of endothelial progenitor cells or decreased platelet aggregation

  13. Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy

    Energy Technology Data Exchange (ETDEWEB)

    Camargo, L.M.; França, C.N.; Izar, M.C.; Bianco, H.T.; Lins, L.S.; Barbosa, S.P.; Pinheiro, L.F.; Fonseca, F.A.H. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina, São Paulo, SP, Brasil, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2014-04-15

    It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1aggregation, the amount of circulating endothelial and platelet microparticles, or endothelial progenitor cells. Cardiovascular protection following therapy with simvastatin/ezetimibe seems restricted to lipid changes and improvement of endothelial function not affecting the release of microparticles, mobilization of endothelial progenitor cells or decreased platelet aggregation.

  14. Identification of a response regulator involved in surface attachment, cell-cell aggregation, exopolysaccharide production and virulence in the plant pathogen Xylella fastidiosa.

    Science.gov (United States)

    Voegel, Tanja M; Doddapaneni, Harshavardhan; Cheng, Davis W; Lin, Hong; Stenger, Drake C; Kirkpatrick, Bruce C; Roper, M Caroline

    2013-04-01

    Xylella fastidiosa, the causal agent of Pierce's disease of grapevine, possesses several two-component signal transduction systems that allow the bacterium to sense and respond to changes in its environment. Signals are perceived by sensor kinases that autophosphorylate and transfer the phosphate to response regulators (RRs), which direct an output response, usually by acting as transcriptional regulators. In the X. fastidiosa genome, 19 RRs were found. A site-directed knockout mutant in one unusual RR, designated XhpT, composed of a receiver domain and a histidine phosphotransferase output domain, was constructed. The resulting mutant strain was analysed for changes in phenotypic traits related to biofilm formation and gene expression using microarray analysis. We found that the xhpT mutant was altered in surface attachment, cell-cell aggregation, exopolysaccharide (EPS) production and virulence in grapevine. In addition, this mutant had an altered transcriptional profile when compared with wild-type X. fastidiosa in genes for several biofilm-related traits, such as EPS production and haemagglutinin adhesins. PMID:23186359

  15. Engineering a Dual-Layer Chitosan-Lactide Hydrogel To Create Endothelial Cell Aggregate-Induced Microvascular Networks In Vitro and Increase Blood Perfusion In Vivo.

    Science.gov (United States)

    Kim, Sungwoo; Kawai, Toshiyuki; Wang, Derek; Yang, Yunzhi

    2016-08-01

    Here, we report the use of chemically cross-linked and photo-cross-linked hydrogels to engineer human umbilical vein endothelial cell (HUVEC) aggregate-induced microvascular networks to increase blood perfusion in vivo. First, we studied the effect of chemically cross-linked and photo-cross-linked chitosan-lactide hydrogels on stiffness, degradation rates, and HUVEC behaviors. The photo-cross-linked hydrogel was relatively stiff (E = ∼15 kPa) and possessed more compact networks, denser surface texture, and lower enzymatic degradation rates than the relatively soft, chemically cross-linked hydrogel (E = ∼2 kPa). While both hydrogels exhibited nontoxicity, the soft chemically cross-linked hydrogels expedited the formation of cell aggregates compared to the photo-cross-linked hydrogels. Cells on the less stiff, chemically cross-linked hydrogels expressed more matrix metalloproteinase (MMP) activity than the stiffer, photo-cross-linked hydrogel. This difference in MMP activity resulted in a more dramatic decrease in mechanical stiffness after 3 days of incubation for the chemically cross-linked hydrogel, as compared to the photo-cross-linked one. After determining the physical and biological properties of each hydrogel, we accordingly engineered a dual-layer hydrogel construct consisting of the relatively soft, chemically cross-linked hydrogel layer for HUVEC encapsulation, and the relatively stiff, acellular, photo-cross-linked hydrogel for retention of cell-laden microvasculature above. This dual-layer hydrogel construct enabled a lasting HUVEC aggregate-induced microvascular network due to the combination of stable substrate, enriched cell adhesion molecules, and extracellular matrix proteins. We tested the dual-layer hydrogel construct in a mouse model of hind-limb ischemia, where the HUVEC aggregate-induced microvascular networks significantly enhanced blood perfusion rate to ischemic legs and decreased tissue necrosis compared with both no treatment and

  16. E4 - Energy efficient elevators and escalators. Barriers to and strategies for promoting energy-efficient lift and escalator technologies

    Energy Technology Data Exchange (ETDEWEB)

    Duetschke, Elisabeth; Hirzel, Simon

    2010-02-25

    According to prior findings of the E4 project, considerable savings potential exists both for lifts and escalators that could be realized if appropriate technology is implemented. However, energy-efficient technology is slowly diffusing the market - a phenomenon that could be explained by barriers present in the market. A barrier is defined as a mechanism that inhibits a decision or behavior that appears to be both energy-efficient and economically efficient and thereby prevents investment in energy-efficient technologies. This document has two aims. First, it will identify influential barriers in the European lift and escalator market. This analysis is based on the literature as well as a study including interviews as well as group discussions with relevant stakeholders. Second, strategies and measures to overcome the barriers identified in the first step are outlined. Major barriers to the penetration of energy-efficient technologies identified in this paper include a lack of monitoring energy consumption of installations and a lack of awareness of as well as knowledge about energy-efficient technology. Thus, installations and components are usually chosen without a (comprehensive) assessment of their energy consumption and without considering life-cycle approaches. On top of this, split incentives are a regularly occurring barrier. Various stakeholders are influential in the decisionmaking process about an installation or its components. However, those who will later pay for the energy consumption often are not involved in this process. Moreover, it is important to keep in mind that the number of new lifts and escalators installed each year is relatively low compared to the existing stock. Thus, it is very important to discuss enhancement of energy efficiency also for the existing stock. Based on our analyses, several recommendations are developed in this paper that could contribute to a market transformation in the lift and escalator market. First of all, a

  17. Bacterial Association with Particles: Aggregation to Dissolution

    Digital Repository Service at National Institute of Oceanography (India)

    DeSouza, M.J.B.D.

    stick to phytoplankton cells to form larger particles called marine snow that enhance the sinking flux of organic carbon. However, Smith et al. (1992) and Ploug et al. (1999) found that once the bacteria colonize the aggregate they solubilize... trophic levels of the aquatic food web (Kiorboe et al., 2002). Caron et al. (1982) thought that aggregates are important loci of microbial activity in the water column, similar to the much larger oceanic ?marine snow? aggregates. Marine snow aggregates...

  18. Inhibition of human platelet aggregation by a novel S-nitrosothiol is abolished by haemoglobin and red blood cells in vitro: implications for anti-thrombotic therapy

    OpenAIRE

    Megson, Ian L; Sogo, Naoki; Mazzei, Francesca A; Butler, Anthony R.; Walton, John C; Webb, David J.

    2000-01-01

    S-Nitrosothiols are nitric oxide (NO) donor drugs that have been shown to inhibit platelet aggregation in platelet rich plasma (PRP) in vitro and to inhibit platelet activation in vivo. The aim of this study was to compare the platelet effects of a novel S-nitrosated glyco-amino acid, RIG200, with an established S-nitrosothiol, S-nitrosoglutathione (GSNO) in PRP, and to investigate the effects of cell-free haemoglobin and red blood cells on S-nitrosothiol-mediated inhibition of platelet aggre...

  19. Homotypic aggregation of human cell lines by HLA class II-, class Ia- and HLA-G-specific monoclonal antibodies

    DEFF Research Database (Denmark)

    Odum, Niels; Ledbetter, J A; Martin, P;

    1991-01-01

    two anti-beta 2-microglobulin mAb had variable, weak effects. The aggregation response was an active, temperature-sensitive process which was almost totally abrogated by azide and by cytochalasins B and E, but unaffected by colchicine, EDTA, aphidicolin, actinomycin D and protein tyrosine kinase...

  20. Binding of heavy metal ions in aggregates of microbial cells, EPS and biogenic iron minerals measured in-situ using metal- and glycoconjugates-specific fluorophores

    Science.gov (United States)

    Hao, Likai; Guo, Yuan; Byrne, James M.; Zeitvogel, Fabian; Schmid, Gregor; Ingino, Pablo; Li, Jianli; Neu, Thomas R.; Swanner, Elizabeth D.; Kappler, Andreas; Obst, Martin

    2016-05-01

    Aggregates consisting of bacterial cells, extracellular polymeric substances (EPS) and Fe(III) minerals formed by Fe(II)-oxidizing bacteria are common at bulk or microscale chemical interfaces where Fe cycling occurs. The high sorption capacity and binding capacity of cells, EPS, and minerals controls the mobility and fate of heavy metals. However, it remains unclear to which of these component(s) the metals will bind in complex aggregates. To clarify this question, the present study focuses on 3D mapping of heavy metals sorbed to cells, glycoconjugates that comprise the majority of EPS constituents, and Fe(III) mineral aggregates formed by the phototrophic Fe(II)-oxidizing bacteria Rhodobacter ferrooxidans SW2 using confocal laser scanning microscopy (CLSM) in combination with metal- and glycoconjugates-specific fluorophores. The present study evaluated the influence of glycoconjugates, microbial cell surfaces, and (biogenic) Fe(III) minerals, and the availability of ferrous and ferric iron on heavy metal sorption. Analyses in this study provide detailed knowledge on the spatial distribution of metal ions in the aggregates at the sub-μm scale, which is essential to understand the underlying mechanisms of microbe-mineral-metal interactions. The heavy metals (Au3+, Cd2+, Cr3+, CrO42-, Cu2+, Hg2+, Ni2+, Pd2+, tributyltin (TBT) and Zn2+) were found mainly sorbed to cell surfaces, present within the glycoconjugates matrix, and bound to the mineral surfaces, but not incorporated into the biogenic Fe(III) minerals. Statistical analysis revealed that all ten heavy metals tested showed relatively similar sorption behavior that was affected by the presence of sorbed ferrous and ferric iron. Results in this study showed that in addition to the mineral surfaces, both bacterial cell surfaces and the glycoconjugates provided most of sorption sites for heavy metals. Simultaneously, ferrous and ferric iron ions competed with the heavy metals for sorption sites on the organic

  1. Capital cost escalation and the choice of power stations

    International Nuclear Information System (INIS)

    The UK Energy Commission has endorsed the case for nuclear power at baseload, on the grounds of its reduced vulnerability to fuel price escalation. Yet with a future climate of tighter environmental restrictions and escalating capital costs, nuclear power could be an ominous liability. The increase of AGR construction costs in the UK and LWR costs in the USA and Germany are examined and it is shown that with expanding nuclear power plant material requirements in the last decade costs have risen considerably faster than inflation. Projecting the trend a further decade, as is consistent with US and German estimates, suggests that by 2000 the extra real annual cost of a UK nuclear programme could be Pound2 billion greater than the equivalent coal programme. (author)

  2. STUDY OF PRIVILEGE ESCALATION ATTACK ON ANDROID AND ITS COUNTERMEASURES

    Directory of Open Access Journals (Sweden)

    REJO MATHEW

    2012-09-01

    Full Text Available Android is most commonly used platform for smartphones today which boasts of an advanced security model having MAC and sandboxing. These features allow developers and users to restrict the execution of anapplication to the privileges assigned. The exploitation of vulnerabilities of the program is confined within the privilege boundaries of an applications sandbox. Privilege escalation attacks have grown manifold as the use of android systems have increased. Different kinds of mechanisms have provided some sort of respite to the developers but the security feature handling by the developers has not helped much. In this paper we discuss the basics of the privilege escalation attack and the various techniques used to counter and prevent this problem.

  3. Isolation and measurement of the features of arrays of cell aggregates formed by dielectrophoresis using the user-specified Multi Regions Masking (MRM) technique

    International Nuclear Information System (INIS)

    The use of dielectrophoresis for the construction of artificial skin tissue with skin cells in follicle-like 3D cell aggregates in well-defined patterns is demonstrated. To analyse the patterns produced and to study their development after their formation a Virtual Instrument (VI) system was developed using the LabVIEW IMAQ Vision Development Module. A series of programming functions (algorithms) was used to isolate the features on the image (in our case; the patterned aggregates) and separate them from all other unwanted regions on the image. The image was subsequently converted into a binary version, covering only the desired microarray regions which could then be analysed by computer for automatic object measurements. The analysis utilized the simple and easy-to-use User-Specified Multi-Regions Masking (MRM) technique, which allows one to concentrate the analysis on the desired regions specified in the mask. This simplified the algorithms for the analysis of images of cell arrays having similar geometrical properties. By having a collection of scripts containing masks of different patterns, it was possible to quickly and efficiently develop sets of custom virtual instruments for the offline or online analysis of images of cell arrays in the database.

  4. Isolation and measurement of the features of arrays of cell aggregates formed by dielectrophoresis using the user-specified Multi Regions Masking (MRM) technique

    Energy Technology Data Exchange (ETDEWEB)

    Yusvana, Rama; Markx, Gerard H [School of Engineering and Physical Science, Department of Chemical Engineering, Heriot-Watt University, Riccarton Campus, Edinburgh - EH14 4AS (United Kingdom); Headon, Denis, E-mail: g.h.markx@hw.ac.u [Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian, Edinburgh - EH25 9PS (United Kingdom)

    2009-08-01

    The use of dielectrophoresis for the construction of artificial skin tissue with skin cells in follicle-like 3D cell aggregates in well-defined patterns is demonstrated. To analyse the patterns produced and to study their development after their formation a Virtual Instrument (VI) system was developed using the LabVIEW IMAQ Vision Development Module. A series of programming functions (algorithms) was used to isolate the features on the image (in our case; the patterned aggregates) and separate them from all other unwanted regions on the image. The image was subsequently converted into a binary version, covering only the desired microarray regions which could then be analysed by computer for automatic object measurements. The analysis utilized the simple and easy-to-use User-Specified Multi-Regions Masking (MRM) technique, which allows one to concentrate the analysis on the desired regions specified in the mask. This simplified the algorithms for the analysis of images of cell arrays having similar geometrical properties. By having a collection of scripts containing masks of different patterns, it was possible to quickly and efficiently develop sets of custom virtual instruments for the offline or online analysis of images of cell arrays in the database.

  5. Conflict resolution vs. conflict escalation in online markets

    OpenAIRE

    Gary Bolton; Ben Greiner; Axel ockenfels

    2015-01-01

    Many online markets encourage traders to make good after an unsatisfactory transaction by offering the opportunity of withdrawing negative reputational feedback in a conflict resolution phase. Motivated by field evidence and guided by theoretical considerations, we use laboratory markets with two-sided moral hazard to show that this option, contrary to the intended purpose, produces an escalation of conflict in the form of strategically distorted reputation information and less trust and trus...

  6. STUDY OF PRIVILEGE ESCALATION ATTACK ON ANDROID AND ITS COUNTERMEASURES

    OpenAIRE

    REJO MATHEW

    2012-01-01

    Android is most commonly used platform for smartphones today which boasts of an advanced security model having MAC and sandboxing. These features allow developers and users to restrict the execution of anapplication to the privileges assigned. The exploitation of vulnerabilities of the program is confined within the privilege boundaries of an applications sandbox. Privilege escalation attacks have grown manifold as the use of android systems have increased. Different kinds of mechanisms have ...

  7. International terrorism, political instability and the escalation effect

    OpenAIRE

    Nauro F. Campos; Gassebner, Martin

    2009-01-01

    What are the main causes of international terrorism? The lessons from the surge of academic research that followed 9/11 remain elusive. The careful investigation of the relative roles of economic and political conditions did little to change the fact that existing econometric estimates diverge in size, sign and significance. In this paper we present a new rationale (the escalation effect) stressing domestic political instability as the main reason for international terrorism. Econometric evid...

  8. Training Tolerance to Delay Using the Escalating Interest Task

    OpenAIRE

    Rung, Jillian M.; Young, Michael E.

    2014-01-01

    The present study examined the lasting effects of exposure to reinforcement that increased in magnitude as a function of time between responses in a first-person shooter video game preparation of the escalating interest task. When reinforcement density increased as a function of time, it encouraged participants to wait longer between responses (shots of a weapon). Participants exposed to such contingencies waited significantly longer to fire their weapons than participants who were exposed to...

  9. A dose-escalation study of indisulam in combination with capecitabine (Xeloda) in patients with solid tumours

    OpenAIRE

    Siegel-Lakhai, W S; Zandvliet, A S; Huitema, A D R; Tibben, M. M.; Milano, G.; Girre, V.; Diéras, V; King, A; Richmond, E; Wanders, J.; Beijnen, J H; Schellens, J H M

    2008-01-01

    This dose escalation study was designed to determine the recommended dose of the multi-targeted cell cycle inhibitor indisulam in combination with capecitabine in patients with solid tumours and to evaluate the pharmacokinetics of the combination. Thirty-five patients were treated with indisulam on day 1 of each 21-day cycle. Capecitabine was administered two times daily (BID) on days 1–14. Plasma concentrations of indisulam, capecitabine and its three metabolites were determined for pharmaco...

  10. Migration, Occupational Mobility, and Regional Escalators in Scotland

    Directory of Open Access Journals (Sweden)

    Maarten van Ham

    2012-01-01

    Full Text Available This paper seeks to unpick the complex relationship between an individual’s migration behaviour, their place of residence, and their occupational performance in the Scottish labour market between 1991 and 2001. We investigate whether Edinburgh has emerged as an occupational escalator region and whether individuals moving there experience more rapid upward occupational mobility than those living and moving elsewhere. Using country of birth, we also control for an individual’s propensity to make long distance moves during earlier periods of their life course. Using data from the Scottish Longitudinal Study, linking 1991 and 2001 individual census records, and logistic regressions, we show that those who migrate over long distances within or to Scotland are most likely to achieve upward occupational mobility. We also found that Edinburgh is by far the most important regional escalator in Scotland; those moving to Edinburgh are the most likely to experience upward occupational mobility from low to high occupational status jobs. This is an important finding as most of the literature on escalator regions focuses on international mega cities.

  11. Aggregation of Scale Efficiency

    OpenAIRE

    Valentin Zelenyuk

    2012-01-01

    In this article we extend the aggregation theory in efficiency and productivity analysis by deriving solutions to the problem of aggregation of individual scale efficiency measures, primal and dual, into aggregate primal and dual scale efficiency measures of a group. The new aggregation result is coherent with aggregation framework and solutions for the other related efficiency measures that already exist in the literature.

  12. Final technical report for project titled Quantitative Characterization of Cell Aggregation/Adhesion as Predictor for Distribution and Transport of Microorganisms in Subsurface Environment

    Energy Technology Data Exchange (ETDEWEB)

    Gu, April Z [Northeastern University; Wan, Kai-tak [Northeastern Univeristy

    2014-09-02

    This project aims to explore and develop enabling methodology and techniques for nano-scale characterization of microbe cell surface contact mechanics, interactions and adhesion quantities that allow for identification and quantification of indicative properties related to microorganism migration and transport behavior in porous media and in subsurface environments. Microbe transport has wide impact and therefore is of great interest in various environmental applications such as in situ or enhanced subsurface bioremediation,filtration processes for water and wastewater treatments and protection of drinking water supplies. Although great progress has been made towards understanding the identities and activities of these microorganisms in the subsurface, to date, little is known of the mechanisms that govern the mobility and transport of microorganisms in DOE’s contaminated sites, making the outcomes of in situ natural attenuation or contaminant stability enhancement unpredictable. Conventionally, movement of microorganisms was believed to follows the rules governing solute (particle) transport. However, recent studies revealed that cell surface properties, especially those pertaining to cell attachment/adhesion and aggregation behavior, can cause the microbe behavior to deviate from non-viable particles and hence greatly influence the mobility and distribution of microorganisms in porous media.This complexity highlights the need to obtain detailed information of cell-cell and cell-surface interactions in order to improve and refine the conceptual and quantitative model development for fate and transport of microorganisms and contaminant in subsurface. Traditional cell surface characterization methods are not sufficient to fully predict the deposition rates and transport behaviors of microorganism observed. A breakthrough of methodology that would allow for quantitative and molecular-level description of intrinsic cell surface properties indicative for cell

  13. The effects of fixed versus escalating reinforcement schedules on smoking abstinence.

    Science.gov (United States)

    Romanowich, Paul; Lamb, R J

    2015-01-01

    Studies indicate that when abstinence is initiated, escalating reinforcement schedules maintain continuous abstinence longer than fixed reinforcement schedules. However, these studies were conducted for shorter durations than most clinical trials and also resulted in larger reinforcer value for escalating participants during the 1st week of the experiment. We tested whether escalating reinforcement schedules maintained abstinence longer than fixed reinforcement schedules in a 12-week clinical trial. Smokers (146) were randomized to an escalating reinforcement schedule, a fixed reinforcement schedule, or a control condition. Escalating reinforcement participants received $5.00 for their first breath carbon monoxide (CO) sample reinforcement participants received $19.75 for each breath CO sample reinforcement participants met the breath CO criterion at least once. Escalating reinforcement participants maintained criterion breath CO levels longer than fixed reinforcement and control participants. Similar to previous short-term studies, escalating reinforcement schedules maintained longer durations of abstinence than fixed reinforcement schedules during a clinical trial. PMID:25640764

  14. The Role of the Midmolecular Peptides in the Blood Cell Aggregation in Acute Periods of a Burn Disease

    OpenAIRE

    Egorikhina M.N.; Levin G.Ya.

    2011-01-01

    The aim of the investigation is to study the effect of midmolecular peptide (MMP) concentration on platelet and erythrocyte aggregation in severe burned patients. Materials and Methods. The investigation was carried out on 34 blood samples of healthy people and 30 blood samples of severe burned patients. There was determined the level of MMP, as well as that of creatinine, and urea. The “Amicon Ultra-4” microcentrifuge tubes were used to isolate MMP. Results. The level increase of ave...

  15. Controlling solution-phase polymer aggregation with molecular weight and solvent additives to optimize polymer-fullerene bulk heterojunction solar cells

    KAUST Repository

    Bartelt, Jonathan A.

    2014-03-20

    The bulk heterojunction (BHJ) solar cell performance of many polymers depends on the polymer molecular weight (M n) and the solvent additive(s) used for solution processing. However, the mechanism that causes these dependencies is not well understood. This work determines how M n and solvent additives affect the performance of BHJ solar cells made with the polymer poly(di(2-ethylhexyloxy)benzo[1,2-b:4,5-b\\']dithiophene-co- octylthieno[3,4-c]pyrrole-4,6-dione) (PBDTTPD). Low M n PBDTTPD devices have exceedingly large fullerene-rich domains, which cause extensive charge-carrier recombination. Increasing the M n of PBDTTPD decreases the size of these domains and significantly improves device performance. PBDTTPD aggregation in solution affects the size of the fullerene-rich domains and this effect is linked to the dependency of PBDTTPD solubility on M n. Due to its poor solubility high M n PBDTTPD quickly forms a fibrillar polymer network during spin-casting and this network acts as a template that prevents large-scale phase separation. Furthermore, processing low M n PBDTTPD devices with a solvent additive improves device performance by inducing polymer aggregation in solution and preventing large fullerene-rich domains from forming. These findings highlight that polymer aggregation in solution plays a significant role in determining the morphology and performance of BHJ solar cells. The performance of poly(di(2-ethylhexyloxy) benzo[1,2-b:4,5-b\\']dithiophene-co-octylthieno[3,4-c]pyrrole-4,6-dione) (PBDTTPD) bulk heterojunction solar cells strongly depends on the polymer molecular weight, and processing these bulk heterojunctions with a solvent additive preferentially improves the performance of low molecular weight devices. It is demonstrated that polymer aggregation in solution significantly impacts the thin-film bulk heterojunction morphology and is vital for high device performance. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. pH-Sensitive polymer assisted self-aggregation of bis(pyrene) in living cells in situ with turn-on fluorescence

    Science.gov (United States)

    Duan, Zhongyu; Gao, Yu-Juan; Qiao, Zeng-Ying; Qiao, Shenglin; Wang, Yongmei; Hou, Chunyuan; Wang, Lei; Wang, Hao

    2015-09-01

    Supramolecular self-assemblies with various nanostructures in organic and aqueous solutions have been prepared with desired functions. However, in situ construction of self-assembled superstructures in physiological conditions to achieve expected biological functions remains a challenge. Here, we report a supramolecular system to realize the in situ formation of nanoaggregates in living cells. The bis(pyrene) monomers were dispersed inside of hydrophobic domains of pH-sensitive polymeric micelles and delivered to the lysosomes of cells. In the acidic lysosomes, the bis(pyrene) monomers were released and self-aggregated with turn-on fluorescence. We envision this strategy for in situ construction of supramolecular nanostructures in living cells will pave the way for molecular diagnostics in the future.

  17. Reinjury risk of nano-calcium oxalate monohydrate and calcium oxalate dihydrate crystals on injured renal epithelial cells: aggravation of crystal adhesion and aggregation

    Directory of Open Access Journals (Sweden)

    Gan QZ

    2016-06-01

    , and cell death rate increased.Conclusion: Cell injury contributes to crystal adhesion to Vero cell surface. The attached nano-COM and COD crystals can aggravate Vero cell injury. As a consequence, crystal adhesion and aggregation are enhanced. These findings provide further insights into kidney stone formation. Keywords: nano-calcium oxalate crystals, cell injury, crystal adhesion, kidney stones

  18. Hydrogel Microwell Arrays Allow the Assessment of Protease-Associated Enhancement of Cancer Cell Aggregation and Survival

    OpenAIRE

    Dietmar W. Hutmacher; Lutolf, Matthias P.; Daniela Loessner; Judith A. Clements; Stefan Kobel

    2013-01-01

    Current routine cell culture techniques are only poorly suited to capture the physiological complexity of tumor microenvironments, wherein tumor cell function is affected by intricate three-dimensional (3D), integrin-dependent cell-cell and cell-extracellular matrix (ECM) interactions. 3D cell cultures allow the investigation of cancer-associated proteases like kallikreins as they degrade ECM proteins and alter integrin signaling, promoting malignant cell behaviors. Here, we employed a hydrog...

  19. Glycation precedes lens crystallin aggregation

    International Nuclear Information System (INIS)

    Non-enzymatic glycosylation (glycation) seems to have the potential to alter the structure of crystallins and make them susceptible to thiol oxidation leading to disulfide-linked high molecular weight (HMW) aggregate formation. They used streptozotocin diabetic rats during precataract and cataract stages and long-term cell-free glycation of bovine lens crystallins to study the relationship between glycation and lens crystallin aggregation. HMW aggregates and other protein components of the water-soluble (WS) and urea-soluble (US) fractions were separated by molecular sieve high performance liquid chromatography. Glycation was estimated by both [3H]NaBH4 reduction and phenylboronate agarose affinity chromatography. Levels of total glycated protein (GP) in the US fractions were about 2-fold higher than in the WS fractions and there was a linear increase in GP in both WS and US fractions. This increase was parallelled by a corresponding increase in HMW aggregates. Total GP extracted by the affinity method from the US fraction showed a predominance of HMW aggregates and vice versa. Cell-free glycation studies with bovine crystallins confirmed the results of the animals studies. Increasing glycation caused a corresponding increase in protein insolubilization and the insoluble fraction thus formed also contained more glycated protein. It appears that lens protein glycation, HMW aggregate formation, and protein insolubilization are interrelated

  20. CONTROL SYSTEM FOR ESCALATOR = SISTEMA DE CONTROLE PARA ESCADA ROLANTE

    Directory of Open Access Journals (Sweden)

    Mauricio Ginez Romero

    2010-01-01

    Full Text Available Many business stablisment utilize escalator that performs it’s function in a regular way of work. There is a big waste of eletric power, as in a good part of it there isn’t a transportation of user. The search for new sources shouldnt’t is the only worry in the context of energetic resource, but also the development of new technologies aimed an optimal use of this recourse. In the conjuncture, this project aims to establish a escalators’ control system, to optimize their use and reduce energy consumption of equipment. The system’s operation is based on the principle that, after a time ta,, a free flow of user, which this time is previously define by a statistician study the escalator reduce its speed, if it has passed a time tb, being tb>ta, the escalator is stopped. If we have the presence of the user, the escalator presents low acceleration, establishing the regular way of work without risks of utilization. The energetic economy happens when the escalator is stopped, or working with reduced speed. The project consists in replace the eletric command of the reversor and with the direct start, by a system’s control proposed. The reduction of the energy comsumption was valued by a statistician study, so trough it we can increase the use of the system and stipulate of the economy zone for the escalators with high and low user’s flow. This system is ecologically correct and contribute for the consumption optimized of electric power. = Muitos estabelecimentos comerciais utilizam escadas rolantes que desempenham sua função em regime normal de funcionamento. Existe um grande desperdício de energia elétrica, já que em boa parte não há transporte de usuário. A busca por novas fontes não deve ser a única preocupação no contexto dos recursos energéticos, mas também o desenvolvimento de novas tecnologias que visam o uso otimizado destes recursos. Nesta conjuntura, este projeto visa implantar um sistema de controle para escadas

  1. Guarana (Paullinia cupana Mart.) prevents β-amyloid aggregation, generation of advanced glycation-end products (AGEs), and acrolein-induced cytotoxicity on human neuronal-like cells.

    Science.gov (United States)

    Bittencourt, Leonardo da Silva; Zeidán-Chuliá, Fares; Yatsu, Francini Kiyono Jorge; Schnorr, Carlos Eduardo; Moresco, Karla Suzana; Kolling, Eduardo Antônio; Gelain, Daniel Pens; Bassani, Valquiria Linck; Moreira, José Cláudio Fonseca

    2014-11-01

    Advanced glycation end-products (AGEs) are considered potent molecules capable of promoting neuronal cell death and participating in the development of neurodegenerative disorders such as Alzheimer's disease (AD). Previous studies have shown that AGEs exacerbate β-amyloid (Aβ) aggregation and AGE-related cross-links are also detected in senile plaques. Acrolein (ACR) is an α, β-unsaturated aldehyde found in the environment and thermally processed foods, which can additionally be generated through endogenous metabolism. The role of ACR in AD is widely accepted in the literature. Guarana (Paullinia cupana Mart.) is popularly consumed by the population in Brazil, mainly for its stimulant activity. In the present study, we showed that guarana (10, 100, and 1000 µg/mL) is able to prevent protein glycation, β-amyloid aggregation, in vitro methylglyoxal, glyoxal, and ACR (20 μM)-induced toxicity on neuronal-like cells (SH-SY5Y). Since these are considered typical AD pathological hallmarks, we propose that guarana may deserve further research as a potential therapeutic agent in such a neurodegenerative disease. PMID:24840232

  2. Selective and Sensitive Detection of Heavy Metal Ions in 100% Aqueous Solution and Cells with a Fluorescence Chemosensor Based on Peptide Using Aggregation-Induced Emission.

    Science.gov (United States)

    Neupane, Lok Nath; Oh, Eun-Taex; Park, Heon Joo; Lee, Keun-Hyeung

    2016-03-15

    A fluorescent peptidyl chemosensor for the detection of heavy metal ions in aqueous solution as well as in cells was synthesized on the basis of the peptide receptor for the metal ions using an aggregation-induced emission fluorophore. The peptidyl chemosensor (1) bearing tetraphenylethylene fluorophore showed an exclusively selective turn-on response to Hg(2+) among 16 metal ions in aqueous buffered solution containing NaCl. The peptidyl chemosensor complexed Hg(2+) ions and then aggregated in aqueous buffered solution, resulting in the significant enhancement (OFF-On) of emissions at around 470 nm. The fluorescent sensor showed a highly sensitive response to Hg(2+), and about 1.0 equiv of Hg(2+) was enough for the saturation of the emission intensity change. The detection limit (5.3 nM, R(2) = 0.99) of 1 for Hg(2+) ions was lower than the maximum allowable level of Hg(2+) in drinking water by EPA. Moreover, the peptidyl chemosensor penetrated live cells and detected intracellular Hg(2+) ions by the turn-on response. PMID:26872241

  3. Caché de directorio multinivel escalable para CMP NUCAs

    OpenAIRE

    VALLS MOMPÓ, JOAN JOSEP

    2012-01-01

    El propósito de este proyecto es diseñar y evaluar por medio de simulación una nueva estructura de directorio más escalable que los esquemas de caché de directorio tradicionalmente utilizados, así como otros publicados en el estado del arte. El diseño propuesto se basa en la observación de que un elevado número de bloques tan solo son accedidos por la caché privada de un único procesador. Estos bloques muestran un comportamiento muy diferente al de los bloques compartidos por v...

  4. Influence of shear stress on erythrocyte aggregation.

    Science.gov (United States)

    Kim, Jeong-Ho; Lee, Hoyoon; Lee, Byoung-Kwon; Shin, Sehyun

    2015-09-25

    Shear stress is known to induce platelet activation and aggregation. The red blood cell (RBC) aggregation test requires the application of shear stress for the cells to disaggregate for initialization. We tested the hypothesis that applying shear stress may activate platelets, which can influence RBC aggregation. The present study used a commercial microchip-based aggregometer (RheoSCan-AnD300) with a rotating stirrer for RBC disaggregation. Whole blood samples were exposed to different magnitudes of shear stress with various shearing times. As the rotational speed was increased up to 2800 rpm, the RBC aggregation index (AI) of the whole blood increased by up to 30% (p <  0.05), whereas that of the platelet-excluded blood samples did not show any apparent alteration. The AI also increased in proportion with the stirring time. The data suggest that high shear stress affects RBC aggregation through shear-induced platelet aggregation. PMID:26444600

  5. THE EFFECTS OF FIXED VERSUS ESCALATING REINFORCEMENT SCHEDULES ON SMOKING ABSTINENCE

    OpenAIRE

    Romanowich, Paul; Lamb, R J

    2015-01-01

    Studies indicate that when abstinence is initiated, escalating reinforcement schedules maintain continuous abstinence longer than fixed reinforcement schedules. However, these studies were conducted for shorter durations than most clinical trials and also resulted in larger reinforcer value for escalating participants during the 1st week of the experiment. We tested whether escalating reinforcement schedules maintained abstinence longer than fixed reinforcement schedules in a 12-week clinical...

  6. Consistent Trade Policy Aggregation

    OpenAIRE

    Anderson, James E.

    2008-01-01

    Much empirical work requires the aggregation of policies. This paper provides methods of policy aggregation that are consistent with two common objectives of empirical work. One is to preserve real income. The other is to preserve the real volume of activity in one or more parts of the economy. Trade policy aggregation is an acute example of the aggregation problem with thousands of highly dispersed trade barriers to be aggregated. An application to India shows that the standard atheoretic me...

  7. Consistency in Aggregation

    OpenAIRE

    Ludwig Auer

    2004-01-01

    In empirical economic research, individual prices are often aggregated into average prices of sub-aggregates. Then, these average prices are aggregated to produce the average price of the total aggregate. Often, such two stage procedures help to illuminate the underlying forces driving the overall result. Since price data are usually published as price changes, this two stage aggregation is typically based on some price index formula. In this paper, various screening devices are introduced wh...

  8. Information-aggregation bias

    OpenAIRE

    Goodfriend, Marvin

    1991-01-01

    Aggregation in the presence of data-processing lags distorts the information content of data, violating orthogonality restrictions that hold at the individual level. Though the phenomenon is general, it is illustrated here for the life-cycle-permanent-income model. Cross-section and pooled-panel data induce information-aggregation bias akin to that in aggregate time series. Calculations show that information aggregation can seriously bias tests of the life-cycle model on aggregate time series...

  9. Visual detection of cancer cells by colorimetric aptasensor based on aggregation of gold nanoparticles induced by DNA hybridization.

    Science.gov (United States)

    Borghei, Yasaman-Sadat; Hosseini, Morteza; Dadmehr, Mehdi; Hosseinkhani, Saman; Ganjali, Mohammad Reza; Sheikhnejad, Reza

    2016-01-21

    A simple but highly sensitive colorimetric method was developed to detect cancer cells based on aptamer-cell interaction. Cancer cells were able to capture nucleolin aptamers (AS 1411) through affinity interaction between AS 1411 and nucleolin receptors that are over expressed in cancer cells, The specific binding of AS 1411 to the target cells triggered the removal of aptamers from the solution. Therefore no aptamer remained in the solution to hybridize with complementary ssDNA-AuNP probes as a result the solution color is red. In the absence of target cells or the presence of normal cells, ssDNA-AuNP probes and aptamers were coexisted in solution and the aptamers assembled DNA-AuNPs, produced a purple solution. UV-vis spectrometry demonstrated that this hybridization-based method exhibited selective colorimetric responses to the presence or absence of target cells, which is detectable with naked eye. The linear response for MCF-7 cells in a concentration range from 10 to 10(5) cells was obtained with a detection limit of 10 cells. The proposed method could be extended to detect other cells and showed potential applications in cancer cell detection and early cancer diagnosis. PMID:26724767

  10. IS Project Management and Risk Escalation: Towards A Dynamic Model

    Directory of Open Access Journals (Sweden)

    Angela Y Lin

    2015-03-01

    Full Text Available While the number of substantive investments in IS projects continues to grow, the number of failing projects also continues to increase at an alarming rate. Both the academic and industry literature suggests that inadequate attention to risk and its management continues to be a key factor in project failure. The typical approach taken is to identify and map potential risks, to act as a planning and diagnostic tool, and to prepare a contingency plan has been a factor-based approach. While it remains a valuable tool for mapping anticipated risks the factor-based approach is less effective when viewing project risks as emergent phenomena that un-fold during the course of the project, and require ongoing attention and risk management. In-formed by a case study of a failing university IS development project, this paper focuses on the phenomenon of risk escalation. The case findings suggest that rather than being defined ahead of the project, some project risks may emerge during the project as a consequence of escalation factors that were both antecedent to and a consequence of actual risk management decisions. The article concludes with suggestions as to how project managers can better man-age the emergent rather than static nature of risk phenomena.

  11. [Deaths during asphyxia induced to escalate sexual experience. Case reports].

    Science.gov (United States)

    Okłota, Magdalena; Niemcunowicz-Janica, Anna; Sackiewicz, Adam; Ptaszyńska-Sarosiek, Iwona; Szeremeta, Michał

    2010-01-01

    The authors present two cases of deaths resulting from asphyxia of one of the partners in the act of intercourse to escalate their experience. The first case involved a heterosexual intercourse, in which a 30-year-old woman was led to state of hypoxia through choking and closing respiratory orifices. The other case represented a homosexual intercourse between two men, in which the victim's hands and legs were tied. Moreover, the partner put an open knot around the victim's neck and was holding it controlling the state of asphyxia, while performing an anal intercourse. Both presented victims practiced such paraphilia-associated behaviors in the past. The fact of sexual intercourse was confirmed in both cases by genetic analysis of the man's anus and the woman's oral cavity and vagina. This resulted in finding the genetic material of their partners. Escalating of sexual experience through inducing asphyxia of the nervous system is extremely dangerous and may result in death of one of the sexual partners, what has been proven by the present investigation. PMID:21863736

  12. Effects of Titanium Dioxide Nanoparticle Aggregate Size on Gene Expression

    OpenAIRE

    Junko Okuda-Shimazaki; Saiko Takaku; Koki Kanehira; Shuji Sonezaki; Akiyohshi Taniguchi

    2010-01-01

    Titanium dioxide (titania) nanoparticle aggregation is an important factor in understanding cytotoxicity. However, the effect of the aggregate size of nanoparticles on cells is unclear. We prepared two sizes of titania aggregate particles and investigated their biological activity by analyzing biomarker expression based on mRNA expression analysis. The aggregate particle sizes of small and large aggregated titania were 166 nm (PDI = 0.291) and 596 nm (PDI = 0.417), respectively. These two siz...

  13. The intracellular domain of cadherin-11 is not required for the induction of cell aggregation, adhesion or gap-junction formation.

    Science.gov (United States)

    Braungart, E; Hartman, E; Bechler, K; Höfler, H; Atkinson, M J

    2001-01-01

    The cadherin family of cell adhesion molecules demonstrates calcium-dependent homophilic binding, leading to cellular recognition and adhesion. The adhesion mediated by the classical type I cadherins is strengthened through catenin-mediated coupling of the cytoplasmic domain to the cytoskeleton. This cytoskeletal interaction may not be essential for the adhesion promoted by all cadherins, several of which lack cytosolic catenin-binding sequences. Cadherin-11, a classical cadherin, possesses a cytoplasmic domain that interacts with catenins, but may also occur as a variant form expressing a truncated cytoplasmic domain. To study the role of the cytoplasmic sequence in cadherin-11 mediated adhesion we have constructed and expressed a truncated cadherin-11 protein lacking the cytoplasmic domain and unable to bind beta-catenin. Expression of the truncated cadherin-11 in MDA-MB-435S human mammary carcinoma cells reduced their motility and promoted calcium-dependent cell aggregation, frequent cell contacts, and functional gap-junctions. We conclude that the intracellular catenin-binding domain of cadherin-11, and by inference cytoskeletal interaction, is not required for the initiation and formation of cell adhesion. PMID:11775026

  14. Triglyceride-rich lipoprotein lipolysis increases aggregation of endothelial cell membrane microdomains and produces reactive oxygen species

    OpenAIRE

    Wang, Limin; Sapuri-Butti, Annapoorna R.; Aung, Hnin Hnin; Parikh, Atul N.; Rutledge, John C

    2008-01-01

    Triglyceride-rich lipoprotein (TGRL) lipolysis may provide a proinflammatory stimulus to endothelium. Detergent-resistant plasma membrane microdomains (lipid rafts) have a number of functions in endothelial cell inflammation. The mechanisms of TGRL lipolysis-induced endothelial cell injury were investigated by examining endothelial cell lipid rafts and production of reactive oxygen species (ROS). Lipid raft microdomains in human aortic endothelial cells were visualized by confocal microscopy ...

  15. THE CELLS WITH MYCOBACTERIA IN GRANULOMATOUS AGGREGATES FROM MICE WITH LATENT TUBERCULOUS INFECTION IN EX VIVO CULTURE

    Directory of Open Access Journals (Sweden)

    E. G. Ufimtseva

    2014-07-01

    Full Text Available Abstract. The aim of this study was to obtain ex vivo monolayer culture cells migrated from individual granulomas isolated from the spleens of the Balb/c line mice through 1–2 months after BCG vaccine infection. The second goal was to evaluate influence of different types of cells in the development of granulomatic inflammation and analysis of BCG bacteria content in these cells in the latent stage of tuberculosis. Granulomas were presented by macrophages in general. The number of granulomas was varied as in one mouse as between mice. Granulomas contained also dendritic cells (in average 10% from macrophages of granulomas and lymphocytes. In some granulomas fibroblasts, neutrophils, eosiniphils, multinuclear cells of Pirogov–Langhans, megacariocytes and platelets were observed in all stages of infection. The number of these cells was also varied between granulomas. The acid staining BCG bacteria were only detected in macrophages, dendritic cells and Pirogov–Langhans cells of mice granulomas. Mice were different as by number of cells with BCG bacteria in granulomas as by number of granulomas with BCG-containing cells. The proposed model of granuloma cells of mice in ex vivo culture can be used to study interaction between host cells and mycobacteria to find new ways and methods of influence to intracellular pathogens in latent stage of tuberculosis. 

  16. Standardization of lyophilization medium for Streptococcus thermophilus subjected to viability escalation on freeze drying

    Directory of Open Access Journals (Sweden)

    Rohit Sharma

    2014-09-01

    Full Text Available The objective of the present study is to develop a lyophilization medium for Streptococcus thermophilus (NCIM 2904 as the industrial exploitation of this bacterium totally depends upon preservation and lyophilization protocols. Protective effect of 18 compounds were observed individually and in combinations with different sugars, sugar alcohols, polymers, protein concentrates and buffers. Among all the protectants tested, ammonium citrate (1% w/w, K2HPO4 (1% w/w and KH2PO4 (1% w/w provided lowest protection to these bacterial cells while 10% (w/w sodium caseinate, whey protein concentrate, sweet whey powder, and skim milk showed significant results in viability escalation. Survival in carbon sources like lactose, sucrose and maltodextrine was also favored maximally. Combination of sodium caseinate 10%, skim milk 5%, sucrose 5%, lactose 5% and mono sodium glutamate 1% in distilled water in ratio of 1:5 with S. thermophilus showed survival percentage of 96%.

  17. The risk-escalation model: a principled design strategy for early-phase trials.

    Science.gov (United States)

    Hey, Spencer Phillips; Kimmelman, Jonathan

    2014-06-01

    Should first-in-human trials be designed to maximize the prospect of therapeutic benefit for volunteers, prioritize avoidance of unintended harms, or aim for some happy medium between the two? Perennial controversies surrounding initiation and design of early-phase trials hinge on how this question is resolved. In this paper, we build on the premise that the task of early-phase testing is to optimize various components of a potential therapy so that later, confirmatory trials have the maximal probability of informing drug development and clinical care. We then explore three strategies that investigators might use to manage trial risks while optimizing a therapy, using cell therapy for Amyotrophic Lateral Sclerosis (ALS) as an example. We argue that an iterative application of maximin strategies over successive cohorts and trials, which we call the "risk-escalation model," establishes a moral principle that should guide decision-making in early-phase trials. PMID:25109092

  18. Aggregation Dynamics Using Phase Wave Signals and Branching Patterns

    Science.gov (United States)

    Sakaguchi, Hidetsugu; Kusagaki, Takuma

    2016-09-01

    The aggregation dynamics of slime mold is studied using coupled equations of phase ϕ and cell concentration n. Phase waves work as tactic signals for aggregation. Branching structures appear during the aggregation. A stationary branching pattern appears like a river network, if cells are uniformly supplied into the system.

  19. Increasing Use of Dose-Escalated External Beam Radiation Therapy for Men With Nonmetastatic Prostate Cancer

    International Nuclear Information System (INIS)

    Purpose: To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. Methods and Materials: We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Using multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. Results: Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. Conclusions: Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment

  20. Studies on the mechanisms of activation of potassium efflux and receptor-cytoskeleton association by aggregated immunoglobulin E-receptor complexes on rat basophilic leukemia cells

    International Nuclear Information System (INIS)

    Evidence for the activation of an outwardly-directed K+ permeability pathway was obtained by studying changes in plasma membrane potential that result from the aggregation of immunoglobulin E-complexes on rat basophilic leukemia cells. With the potential-sensitive dye, bisoxonol, we observe that activation by multivalent antigen causes membrane depolarization that is followed by a return towards the resting potential that we term repolarization. The depolarization response may reflect a Ca2+ influx pathway, and it exhibits the same antigen-dose dependence and temperature dependence as the degranulation response. The polarization phase of the membrane potential response is selectively inhibited by the K+ channel blockers quinidine and Ba2+ in parallel with their inhibition of the degranulation response, suggesting an important role for a K+ efflux pathway in antigen-stimulated degranulation. 86Rb+ efflux measurements were used to characterize the K+ permeability pathways responsible for the repolarization response

  1. Audience reactions to peace journalism: How supporters and critics of the Israeli policy process escalation and de-escalation oriented media frames

    OpenAIRE

    Stephanie Thiel; Wilhelm Kempf

    2014-01-01

    This paper reports on an experiment that uses the Israeli-Palestinian conflict as a natural laboratory for studying how recipients make sense of escalation vs. de-escalation oriented news articles. The results of the study indicate that media frames and individual frames have both a direct effect and complex interaction effects on participants’ text understanding. Particularly the effect of media war frames diminishes if they are incongruent with participants’ individual frames, and the propa...

  2. Audience reactions to peace journalism : how supporters and critics of the Israeli policy process escalation and de-escalation oriented media frames

    OpenAIRE

    Thiel, Stephanie; Kempf, Wilhelm

    2014-01-01

    This paper reports on an experiment that uses the Israeli-Palestinian conflict as a natural laboratory for studying how recipients make sense of escalation vs. de-escalation oriented news articles. The results of the study indicate that media frames and individual frames have both a direct effect and complex interaction effects on participants' text understanding. Particularly the effect of media war frames diminishes if they are incongruent with participants' individual frames, and the propa...

  3. Misonidazole with dexamethasone rescue: an escalating dose toxicity study

    International Nuclear Information System (INIS)

    Neurotoxicity induced by misonidazole (MISO) and desmethylmisonidazole (DMM) has become the dose limiting factor in clinical work. In 1981, the authors reported a preliminary study suggestive that Dexamethasone (DEXA) does have a protective effect against peripheral neuropathies (PN) resulting from toxicity of misonidazole. The authors are presently investigating the use of DEXA, with escalating doses of MISO in an attempt to modify its neurotoxicity. To date, 16 patients have been registered to receive total doses of MISO given in 9 equally divided doses over 3 weeks. DEXA is given 3 days prior to the first dose and continues for the duration of therapy. All patients receive palliative radiation. No toxicity was seen at the total dose of 13.5 gm/M2. One grade I PN occurred in the first four patients receiving 15.5 gm/M2. Six additional patients were entered at this dose level and no further incidence of PN was observed

  4. Taurine and platelet aggregation

    International Nuclear Information System (INIS)

    Taurine is a putative neurotransmitter or neuromodulator. The endogenous taurine concentration in human platelets, determined by amino acid analysis, is 15 μM/g. In spite of this high level, taurine is actively accumulated. Uptake is saturable, Na+ and temperature dependent, and suppressed by metabolic inhibitors, structural analogues, and several classes of centrally active substances. High, medium and low affinity transport processes have been characterized, and the platelet may represent a model system for taurine transport in the CNS. When platelets were incubated with 14C-taurine for 30 minutes, then resuspended in fresh medium and reincubated for one hour, essentially all of the taurine was retained within the cells. Taurine, at concentrations ranging from 10-1000 μM, had no effect on platelet aggregation induced by ADP or epinephrine. However, taurine may have a role in platelet aggregation since 35-39% of the taurine taken up by human platelets appears to be secreted during the release reaction induced by low concentrations of either epinephrine or ADP, respectively. This release phenomenon would imply that part of the taurine taken up is stored directly in the dense bodies of the platelet

  5. Platelet aggregation test

    Science.gov (United States)

    The platelet aggregation blood test checks how well platelets , a part of blood, clump together and cause blood to clot. ... Decreased platelet aggregation may be due to: Autoimmune ... Fibrin degradation products Inherited platelet function defects ...

  6. Aggregation in manpower planning

    OpenAIRE

    Wijngaard, J

    1983-01-01

    In manpower planning, as in all other kinds of planning, an important choice is the level of aggregation. The proper level of aggregation depends on the flexibility (mobility) of the personnel. This dependency is investigated in this paper. The manpower system considered is characterized by two dimensions, level and function group. Conditions are derived for aggregate long-term planning (aggregation over function group) combined with one-period disaggregation being optimal.

  7. Aggregating Reputation Feedback

    OpenAIRE

    Garcin, Florent; Faltings, Boi; Jurca, Radu

    2009-01-01

    A fundamental task in reputation systems is to aggregate multiple feedback ratings into a single value that can be used to compare the reputation of different entities. Feedback is most commonly aggregated using the arithmetic mean. However, the mean is quite susceptible to outliers and biases, and thus may not be the most informative aggregate of the reports. We consider three criteria to assess the quality of an aggregator: the informativness, the robustness and the strategyproofness, and a...

  8. Shaping the Growth Behaviour of Bacterial Aggregates in Biofilms

    CERN Document Server

    Melaugh, Gavin; Kragh, Kasper Nørskov; Irie, Yasuhiko; Roberts, Aled; Bjarnsholt, Thomas; Diggle, Steve P; Gordon, Vernita; Allen, Rosalind J

    2015-01-01

    Bacterial biofilms are usually assumed to originate from individual cells deposited on a surface. However, many biofilm-forming bacteria tend to aggregate in the planktonic phase meaning it is possible that many natural and infectious biofilms originate wholly or partially from pre-formed cell aggregates. Here, we use agent-based computer simulations to investigate the role of pre-formed aggregates in biofilm development. Focusing on the role of aggregate shape, we find that the degree of spreading of an aggregate on a surface can play a key role in determining its eventual fate during biofilm development. Specifically, initially spread aggregates perform better when competition with surrounding bacterial cells is low, while initially rounded aggregates perform better when competition is high. These contrasting outcomes are governed by a trade-off between aggregate surface area and height. Our results provide new insight into biofilm formation and development, and reveal new factors that may be at play in the...

  9. Platelet aggregation following trauma

    DEFF Research Database (Denmark)

    Windeløv, Nis A; Sørensen, Anne M; Perner, Anders;

    2014-01-01

    We aimed to elucidate platelet function in trauma patients, as it is pivotal for hemostasis yet remains scarcely investigated in this population. We conducted a prospective observational study of platelet aggregation capacity in 213 adult trauma patients on admission to an emergency department (ED......). Inclusion criteria were trauma team activation and arterial cannula insertion on arrival. Blood samples were analyzed by multiple electrode aggregometry initiated by thrombin receptor agonist peptide 6 (TRAP) or collagen using a Multiplate device. Blood was sampled median 65 min after injury; median injury...... severity score (ISS) was 17; 14 (7%) patients received 10 or more units of red blood cells in the ED (massive transfusion); 24 (11%) patients died within 28 days of trauma: 17 due to cerebral injuries, four due to exsanguination, and three from other causes. No significant association was found between...

  10. Controlled aggregation of primary human pancreatic islet cells leads to glucose-responsive pseudoislets comparable to native islets

    NARCIS (Netherlands)

    Hilderink, Janneke; Spijker, Siebe; Carlotti, Francoise; Lange, Lydia; Engelse, Marten; van Blitterswijk, Clemens; de Koning, Eelco; Karperien, Marcel; van Apeldoorn, Aart

    2015-01-01

    Clinical islet transplantation is a promising treatment for patients with type 1 diabetes. However, pancreatic islets vary in size and shape affecting their survival and function after transplantation because of mass transport limitations. To reduce diffusion restrictions and improve islet cell surv

  11. Phytoplankton aggregate formation: observations of patterns and mechanisms of cell sticking and the significance of exopolymeric material

    DEFF Research Database (Denmark)

    Kiørboe, Thomas; Hansen, Jorgen L. S.

    1993-01-01

    was that stickiness decreased with age of the batch cultures. We were otherwise unable to establish consistent relationships between cell stickiness and the growth stage of the algae, environmental concentrations of inorganic nutrients, and abundances of suspended and epiphytic bacteria. We showed...

  12. Light-Up Probes Based on Fluorogens with Aggregation-Induced Emission Characteristics for Monoamine Oxidase-A Activity Study in Solution and in Living Cells.

    Science.gov (United States)

    Shen, Wei; Yu, Jiajun; Ge, Jingyan; Zhang, Ruoyu; Cheng, Feng; Li, Xuefeng; Fan, Yong; Yu, Shian; Liu, Bin; Zhu, Qing

    2016-01-13

    Fluorogens with aggregation-induced emission (AIEgens) have emerged as a powerful and versatile platform for the development of novel biosensors. In this study, a series of water-soluble fluorescent probes based on tetraphenylethylene (TPE) were designed and synthesized for the detection of monoamine oxidases (MAOs) based on specific interactions between the probes and the proteins. Among the six probes developed, t-TPEM displays a significant fluorescence increase upon introduction of MAOs. Of particular significance is that the fluorescence of t-TPEM in the presence of MAO-A is 21-fold higher than other proteins including MAO-B. Lineweaver-Burk plots reveal that t-TPEM acts as an uncompetitive inhibitor of MAO-A with Ki = 17.1 μM, which confirms its good binding affinity toward MAO-A. Furthermore, a cell imaging experiment reveals that t-TPEM is able to selectively monitor the activity of MAO-A which is localized in mitochondria of MCF-7 cells. PMID:26666866

  13. Image guided dose escalated prostate radiotherapy: still room to improve

    International Nuclear Information System (INIS)

    Prostate radiotherapy (RT) dose escalation has been reported to result in improved biochemical control at the cost of greater late toxicity. We report on the application of 79.8 Gy in 42 fractions of prostate image guided RT (IGRT). The primary objective was to assess 5-year biochemical control and potential prognostic factors by the Phoenix definition. Secondary endpoints included acute and late toxicity by the Radiotherapy Oncology Group (RTOG) scoring scales. From October/2001 and June/2003, 259 men were treated with at least 2-years follow-up. 59 patients had low, 163 intermediate and 37 high risk disease. 43 had adjuvant hormonal therapy (HT), mostly for high- or multiple risk factor intermediate-risk disease (n = 25). They received either 3-dimensional conformal RT (3DCRT, n = 226) or intensity modulated RT (IMRT) including daily on-line IGRT with intraprostatic fiducial markers. Median follow-up was 67.8 months (range 24.4-84.7). There was no severe (grade 3-4) acute toxicity, and grade 2 acute gastrointestinal (GI) toxicity was unusual (10.1%). The 5-year incidence of grade 2-3 late GI and genitourinary (GU) toxicity was 13.7% and 12.1%, with corresponding grade 3 figures of 3.5% and 2.0% respectively. HT had an association with an increased risk of grade 2-3 late GI toxicity (11% v 21%, p = 0.018). Using the Phoenix definition for biochemical failure, the 5 year-bNED is 88.4%, 76.5% and 77.9% for low, intermediate and high risk patients respectively. On univariate analysis, T-category and Gleason grade correlated with Phoenix bNED (p = 0.006 and 0.039 respectively). Hormonal therapy was not a significant prognostic factor on uni- or multi-variate analysis. Men with positive prostate biopsies following RT had a lower chance of bNED at 5 years (34.4% v 64.3%; p = 0.147). IGRT to 79.8 Gy results in favourable rates of late toxicity compared with published non-IGRT treated cohorts. Future avenues of investigation for toxicity reduction include IMRT, margin

  14. Image guided dose escalated prostate radiotherapy: still room to improve

    Directory of Open Access Journals (Sweden)

    Milosevic Michael

    2009-11-01

    Full Text Available Abstract Background Prostate radiotherapy (RT dose escalation has been reported to result in improved biochemical control at the cost of greater late toxicity. We report on the application of 79.8 Gy in 42 fractions of prostate image guided RT (IGRT. The primary objective was to assess 5-year biochemical control and potential prognostic factors by the Phoenix definition. Secondary endpoints included acute and late toxicity by the Radiotherapy Oncology Group (RTOG scoring scales. Methods From October/2001 and June/2003, 259 men were treated with at least 2-years follow-up. 59 patients had low, 163 intermediate and 37 high risk disease. 43 had adjuvant hormonal therapy (HT, mostly for high- or multiple risk factor intermediate-risk disease (n = 25. They received either 3-dimensional conformal RT (3DCRT, n = 226 or intensity modulated RT (IMRT including daily on-line IGRT with intraprostatic fiducial markers. Results Median follow-up was 67.8 months (range 24.4-84.7. There was no severe (grade 3-4 acute toxicity, and grade 2 acute gastrointestinal (GI toxicity was unusual (10.1%. The 5-year incidence of grade 2-3 late GI and genitourinary (GU toxicity was 13.7% and 12.1%, with corresponding grade 3 figures of 3.5% and 2.0% respectively. HT had an association with an increased risk of grade 2-3 late GI toxicity (11% v 21%, p = 0.018. Using the Phoenix definition for biochemical failure, the 5 year-bNED is 88.4%, 76.5% and 77.9% for low, intermediate and high risk patients respectively. On univariate analysis, T-category and Gleason grade correlated with Phoenix bNED (p = 0.006 and 0.039 respectively. Hormonal therapy was not a significant prognostic factor on uni- or multi-variate analysis. Men with positive prostate biopsies following RT had a lower chance of bNED at 5 years (34.4% v 64.3%; p = 0.147. Conclusion IGRT to 79.8 Gy results in favourable rates of late toxicity compared with published non-IGRT treated cohorts. Future avenues of

  15. Aggregation behavior of tin in tin oxides reacted with lithium

    International Nuclear Information System (INIS)

    Tin aggregation behavior during charge/discharge of tin oxide electrodes is investigated using Li/Sn2BPO6 and Li/SnO cells. Sn aggregation is identified by the peaks in the derivative capacity vs. voltage plot. Scanning electron microscope, transmission electron microscope, and Auger electron spectroscope are used to investigate the formation and growth of Sn aggregates. Sn aggregation is more prominent when the upper cutoff voltage is higher than 1.0 V, and Sn aggregates continues to grow with cycling. The upper cutoff voltage is the most critical factor for Sn aggregation as it governs the size and growth rate of aggregates, whereas the effect of the lower cutoff voltage on Sn aggregation behavior seems relatively insignificant. Sn aggregation shows limited effect on cycling behavior of tin oxide electrode

  16. The influence of toxicity constraints in models of chemotherapeutic protocol escalation

    KAUST Repository

    Boston, E. A. J.

    2011-04-06

    The prospect of exploiting mathematical and computational models to gain insight into the influence of scheduling on cancer chemotherapeutic effectiveness is increasingly being considered. However, the question of whether such models are robust to the inclusion of additional tumour biology is relatively unexplored. In this paper, we consider a common strategy for improving protocol scheduling that has foundations in mathematical modelling, namely the concept of dose densification, whereby rest phases between drug administrations are reduced. To maintain a manageable scope in our studies, we focus on a single cell cycle phase-specific agent with uncomplicated pharmacokinetics, as motivated by 5-Fluorouracil-based adjuvant treatments of liver micrometastases. In particular, we explore predictions of the effectiveness of dose densification and other escalations of the protocol scheduling when the influence of toxicity constraints, cell cycle phase specificity and the evolution of drug resistance are all represented within the modelling. For our specific focus, we observe that the cell cycle and toxicity should not simply be neglected in modelling studies. Our explorations also reveal the prediction that dose densification is often, but not universally, effective. Furthermore, adjustments in the duration of drug administrations are predicted to be important, especially when dose densification in isolation does not yield improvements in protocol outcomes. © The author 2011. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

  17. Destined to die but not to wage war: how existential threat can contribute to escalation or de-escalation of violent intergroup conflict.

    Science.gov (United States)

    Jonas, Eva; Fritsche, Immo

    2013-10-01

    War means threat to people's lives. Research derived from terror management theory (TMT) illustrates that the awareness of death leads people to defend cultural ingroups and their worldviews to attain a sense of symbolic immortality and thereby buffer existential anxiety. This can result in hostile effects of mortality salience (MS), such as derogation of outgroup members, prejudice, stereotyping, aggression, and racism, which, in turn, can lead to the escalation of violent intergroup conflict and, thus, the escalation of war. Yet, escalation of destructive conflict following MS is not automatic. Instead, research on TMT suggests that MS does not necessarily result in conflict and intolerance but can also foster positive tendencies, such as intergroup fairness or approval of pacifism, depending on how existential threat is perceived, whether the need for symbolic self-transcendence is satisfied, which social norms are salient, and how social situations are interpreted. In the present article, we review current TMT research with the aim of reconciling the seemingly contradictory findings of hostile and peaceful reactions to reminders of death. We present a terror management model of escalation and de-escalation of violent intergroup conflicts, which takes into account the interaction between threat salience and features of the social situation. We also discuss possible intervention strategies to override detrimental consequences of existential threat and argue that war is not the inevitable consequence of threat. PMID:24128317

  18. Error Cost Escalation Through the Project Life Cycle

    Science.gov (United States)

    Stecklein, Jonette M.; Dabney, Jim; Dick, Brandon; Haskins, Bill; Lovell, Randy; Moroney, Gregory

    2004-01-01

    It is well known that the costs to fix errors increase as the project matures, but how fast do those costs build? A study was performed to determine the relative cost of fixing errors discovered during various phases of a project life cycle. This study used three approaches to determine the relative costs: the bottom-up cost method, the total cost breakdown method, and the top-down hypothetical project method. The approaches and results described in this paper presume development of a hardware/software system having project characteristics similar to those used in the development of a large, complex spacecraft, a military aircraft, or a small communications satellite. The results show the degree to which costs escalate, as errors are discovered and fixed at later and later phases in the project life cycle. If the cost of fixing a requirements error discovered during the requirements phase is defined to be 1 unit, the cost to fix that error if found during the design phase increases to 3 - 8 units; at the manufacturing/build phase, the cost to fix the error is 7 - 16 units; at the integration and test phase, the cost to fix the error becomes 21 - 78 units; and at the operations phase, the cost to fix the requirements error ranged from 29 units to more than 1500 units

  19. PET-guided dose escalation tomotherapy in malignant pleural mesothelioma

    Energy Technology Data Exchange (ETDEWEB)

    Fodor, Andrei; Dell' Oca, Italo; Pasetti, Marcella; Di Muzio, Nadia Gisella [San Raffaele Scientific Institute, Milan (Italy). Dept. of Radiotherapy; Fiorino, Claudio; Broggi, Sara; Cattaneo, Giovanni Mauro; Calandrino, Riccardo [San Raffaele Scientific Institute, Milan (Italy). Medical Physics; Gianolli, Luigi [San Raffaele Scientific Institute, Milan (Italy). Dept. of Nuclear Medicine

    2011-11-15

    To test the feasibility of salvage radiotherapy using PET-guided helical tomotherapy in patients with progressive malignant pleural mesothelioma (MPM). A group of 12 consecutive MPM patients was treated with 56 Gy/25 fractions to the planning target volume (PTV); FDG-PET/CT simulation was always performed to include all positive lymph nodes and MPM infiltrations. Subsequently, a second group of 12 consecutive patients was treated with the same dose to the whole pleura adding a simultaneous integrated boost of 62.5 Gy to the FDG-PET/CT positive areas (BTV). Good dosimetric results were obtained in both groups. No grade 3 (RTOG/EORTC) acute or late toxicities were reported in the first group, while 3 cases of grade 3 late pneumonitis were registered in the second group: the duration of symptoms was 2-10 weeks. Median overall survival was 8 months (1.2-50.5 months) and 20 months (4.3-33.8 months) from the beginning of radiotherapy, for groups I and II, respectively (p = 0.19). A significant impact on local relapse from radiotherapy was seen (median time to local relapse: 8 vs 17 months; 1-year local relapse-free rate: 16% vs 81%, p = 0.003). The results of this pilot study support the planning of a phase III study of combined sequential chemoradiotherapy with dose escalation to BTV in patients not able to undergo resection. (orig.)

  20. Effect of the surfactant Tween 80 on the detachment and dispersal of Salmonella enterica Thompson single cells and aggregates from cilantro leaves as revealed by image analysis

    Science.gov (United States)

    Biofilms formed by human enteric pathogens on plants are a great concern to the produce industry. Salmonella enterica has the ability to form biofilms and large aggregates on leaf surfaces, including on cilantro leaves. Aggregates that remained attached after rigorous washing of cilantro leaves and ...

  1. Escalation scenarios initiated by gas explosions on offshore installations. Probabilistic cause and consequence modelling

    Energy Technology Data Exchange (ETDEWEB)

    Eknes, Monika Loeland

    1996-12-31

    This Dr. ing. thesis deals with escalation scenarios initiated by gas explosions on offshore installations. Gas explosions is one of the major hazards to such installations. The objectives were to estimate the probability of ignition and frequency of gas explosions for gas leaks on top sides of offshore installations, and to estimate the response and resistance of components that could result in escalation if they failed. Main fields considered cover risk analysis methodology, gas explosions, simplified escalation models, evaluation of structural consequences, case studies, and guidelines. 107 refs., 33 figs., 33 tabs.

  2. The Casimir Effect in Biology: The Role of Molecular Quantum Electrodynamics in Linear Aggregations of Red Blood Cells

    International Nuclear Information System (INIS)

    Despite the fact that red blood cells carry negative charges, under certain conditions they form cylindrical stacks, or 'rouleaux'. It is shown here that a form of the Casimir effect, generalizing the more well-known van der Waals forces, can provide the necessary attractive force to balance the electrostatic repulsion. Erythrocytes in plasma are modelled as negatively charged dielectric disks in an ionic solution, allowing predictions to be made about the conditions under which rouleaux will form. The results show qualitative agreement with observations which suggest that the basic idea is worth further pursuit. In addition to revealing a mechanism which may be widespread in biology at the cellular level, it also suggest new experiments and further applications to other biological systems, colloid chemistry and nanotechnology.

  3. The Casimir Effect in Biology: The Role of Molecular Quantum Electrodynamics in Linear Aggregations of Red Blood Cells

    Energy Technology Data Exchange (ETDEWEB)

    Bradonjic, K [Physics Department, Boston University, Boston MA (United States); Swain, J D; Widom, A; Srivastava, Y N, E-mail: john.swain@cern.c [Physics Department, Northeastern University, Boston MA (United States)

    2009-04-01

    Despite the fact that red blood cells carry negative charges, under certain conditions they form cylindrical stacks, or 'rouleaux'. It is shown here that a form of the Casimir effect, generalizing the more well-known van der Waals forces, can provide the necessary attractive force to balance the electrostatic repulsion. Erythrocytes in plasma are modelled as negatively charged dielectric disks in an ionic solution, allowing predictions to be made about the conditions under which rouleaux will form. The results show qualitative agreement with observations which suggest that the basic idea is worth further pursuit. In addition to revealing a mechanism which may be widespread in biology at the cellular level, it also suggest new experiments and further applications to other biological systems, colloid chemistry and nanotechnology.

  4. The Casimir Effect in Biology: The Role of Molecular Quantum Electrodynamics in Linear Aggregations of Red Blood Cells

    Science.gov (United States)

    Bradonjić, K.; Swain, J. D.; Widom, A.; Srivastava, Y. N.

    2009-04-01

    Despite the fact that red blood cells carry negative charges, under certain conditions they form cylindrical stacks, or "rouleaux". It is shown here that a form of the Casimir effect, generalizing the more well-known van der Waals forces, can provide the necessary attractive force to balance the electrostatic repulsion. Erythrocytes in plasma are modelled as negatively charged dielectric disks in an ionic solution, allowing predictions to be made about the conditions under which rouleaux will form. The results show qualitative agreement with observations which suggest that the basic idea is worth further pursuit. In addition to revealing a mechanism which may be widespread in biology at the cellular level, it also suggest new experiments and further applications to other biological systems, colloid chemistry and nanotechnology.

  5. Competitive aggregation dynamics using phase wave signals.

    Science.gov (United States)

    Sakaguchi, Hidetsugu; Maeyama, Satomi

    2014-10-21

    Coupled equations of the phase equation and the equation of cell concentration n are proposed for competitive aggregation dynamics of slime mold in two dimensions. Phase waves are used as tactic signals of aggregation in this model. Several aggregation clusters are formed initially, and target patterns appear around the localized aggregation clusters. Owing to the competition among target patterns, the number of the localized aggregation clusters decreases, and finally one dominant localized pattern survives. If the phase equation is replaced with the complex Ginzburg-Landau equation, several spiral patterns appear, and n is localized near the center of the spiral patterns. After the competition among spiral patterns, one dominant spiral survives. PMID:24956327

  6. Provenance for Aggregate Queries

    OpenAIRE

    Yael Amsterdamer; Daniel Deutch; Val Tannen

    2011-01-01

    We study in this paper provenance information for queries with aggregation. Provenance information was studied in the context of various query languages that do not allow for aggregation, and recent work has suggested to capture provenance by annotating the different database tuples with elements of a commutative semiring and propagating the annotations through query evaluation. We show that aggregate queries pose novel challenges rendering this approach inapplicable. Consequently, we propose...

  7. Diffusion in aggregated soil.

    OpenAIRE

    Rappoldt, C.

    1992-01-01

    The structure of an aggregated soil is characterized by the distribution of the distance from an arbitrary point in the soil to the nearest macropore or crack. From this distribution an equivalent model system is derived to which a diffusion model can be more easily applied. The model system consists of spherical, or cylindrical or plane aggregates, which do not represent the individual aggregates of the soil, however. The radii of the spheres, cylinders or plane sheets represent different le...

  8. A Ca-alginate particle co-immobilized with Phanerochaete chrysosporium cells and the combined cross-linked enzyme aggregates from Trametes versicolor.

    Science.gov (United States)

    Li, Yanchun; Wang, Zhi; Xu, Xudong; Jin, Liqiang

    2015-12-01

    For improving stability of immobilized white-rot fungus to treat various effluents, Phanerochaete chrysosporium cells and the combined cross-link enzyme aggregates (combi-CLEAs) prepared from Trametes versicolor were co-immobilized into the Ca-alginate gel particles in this paper. The activity yields of obtained combi-CLEAs were 42.7% for lignin peroxidases (LiPs), 31.4% for manganese peroxidases (MnPs) and 40.4% for laccase (Lac), respectively. And their specific activities were 30.2U/g as combi-CLEAs-LiPs, 9.5 U/g as combi-CLEAs-MnPs and 28.4 U/g as combi-CLEAs-Lac. Further, the present of the combi-CLEAs in the particles extremely improved their ability to degrade the dyes. Compared to the immobilized Ph. chrysosporium without the combi-CLEAs, the co-immobilized particles enhanced the decolorized rate of Acid Violet 7 (from 45.2% to 93.4%) and Basic Fuchsin (from 12.1% to 67.9%). In addition, the addition of the combi-CLEAs improved the adaptability of the white-rot fungal particles to adverse environmental conditions. PMID:26413897

  9. The Aggregate-Supply/Aggregate-Demand Model

    OpenAIRE

    BARRO, Robert J.

    1994-01-01

    The aggregate-supply/ aggregate-demand (AS-AD) model is popular in textbooks, but has problems with logical consistency. In one interpretation, the Keynesian underpinnings of the AD curve-derived from the IS/LM model with downward price stickiness-conflict with the determination of the price level at the intersection of the AS and AD curves. In another view, the model corresponds to rational-expectations theories in which Keynesian properties are absent. In a third interpretation, the model i...

  10. Organizational Conflict Management as Disputing Process: The Problem of Social Escalation.

    Science.gov (United States)

    Morrill, Calvin; Thomas, Cheryl King

    1992-01-01

    Develops an instrument to study organizational conflict management as a disputing process involving the social escalation from grievance to conflict and dispute stages. Finds differences in dispute process according to different strengths of informal relations. (SR)

  11. Antigen dose escalation study of a VEGF-based therapeutic cancer vaccine in non human primates.

    Science.gov (United States)

    Morera, Yanelys; Bequet-Romero, Mónica; Ayala, Marta; Pérez, Pedro Puente; Castro, Jorge; Sánchez, Javier; Alba, José Suárez; Ancízar, Julio; Cosme, Karelia; Gavilondo, Jorge V

    2012-01-01

    CIGB-247 is a cancer therapeutic, based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, in combination with the oil free adjuvant VSSP (very small sized proteoliposomes of Neisseria meningitidis outer membrane). Our previous experimental studies in mice with CIGB-247 have shown that the vaccine has both anti-tumoral and anti-metastatic activity, and produces both antibodies that block VEGF-VEGF receptor interaction, and a specific T-cell cytotoxic response against tumor cells. CIGB-247, with an antigen dose of 100 μg, has been characterized by an excellent safety profile in mice, rats, rabbits, and non human primates. In this article we extend the immunogenicity and safety studies of CIGB-247 in non human primates, scaling the antigen dose from 100 μg to 200 and 400 μg/vaccination. Our results indicate that such dose escalation did not affect animal behavior, clinical status, and blood parameters and biochemistry. Also, vaccination did not interfere with skin deep skin wound healing. Anti-VEGF IgG antibodies and specific T-cell mediated responses were documented at all three studied doses. Antigen dose apparently did not determine differences in maximum antibody titer during the 8 weekly immunization induction phase, or the subsequent increase in antibodies seen for monthly boosters delivered afterwards. Higher antigen doses had a positive influence in antibody titer maintenance, after cessation of immunizations. Boosters were important to achieve maximum antibody VEGF blocking activity, and specific T-cell responses in all individuals. Purified IgG from CIGB-247 immunized monkey sera was able to impair proliferation and formation of capillary-like structures in Matrigel, for HMEC cells in culture. Altogether, these results support the further clinical development of the CIGB-247 therapeutic cancer vaccine, and inform on the potential mechanisms involved in its effect. PMID:22075086

  12. An Aggregation Matrix MATLAB Function

    OpenAIRE

    Caleb Stair

    2013-01-01

    This Technical Document describes the foundations for an aggregation matrix function implemented in MATLAB, including the format and structure of the required aggregation vector used as an argument to the function. The function is passed with the N-dimensional aggregation vector as an argument. The aggregation vector contains N values ranging from 1 to M, each of which is the aggregate index corresponding to the N pre-aggregation indices. The function returns an aggregation matrix with M rows...

  13. DOES CONSISTENT AGGREGATION REALLY MATTER?

    OpenAIRE

    Shumway, C. Richard; Davis, George C.

    2000-01-01

    Consistent aggregation assures that behavioral properties which apply to disaggregate relationships also apply to aggregate relationships. The agricultural economics literature is reviewed which has tested for consistent aggregation or measured statistical bias and/or inferential errors due to aggregation. Tests for aggregation bias and errors of inference are conducted using indices previously tested for consistent aggregation. Failure to reject consistent aggregation in a partition did not ...

  14. DOES CONSISTENT AGGREGATION REALLY MATTER?

    OpenAIRE

    Shumway, C. Richard; Davis, George C.

    2000-01-01

    Consistent aggregation assures that behavioral properties, which apply to disaggregate relationships also, apply to aggregate relationships. The agricultural economics literature is reviewed which has tested for consistent aggregation or measured statistical bias and/or inferential errors due to aggregation. Tests for aggregation bias and errors of inference are conducted using indices previously tested for consistent aggregation. Failure to reject consistent aggregation in a partition did no...

  15. Scenario based analysis of fire escalation in a gas process plant

    OpenAIRE

    Bjørge, Joachim Søreng

    2013-01-01

    This study takes place on a medium sized gas process plant called reference plant. In this thesis several escalation scenarios, as well as gas dispersion, is evaluated through Kameleon KFX and Vessfire. It has previously been conducted similar escalation studies. However, a normal approach to conduct these studies is to use reference values of a uniform property for heat flux both global and peak, and will only record/evaluate if rupture occurs. In this thesis uses every scenario tran...

  16. Effect of the Surfactant Tween 80 on the Detachment and Dispersal of Salmonella enterica Serovar Thompson Single Cells and Aggregates from Cilantro Leaves as Revealed by Image Analysis

    OpenAIRE

    Maria T Brandl; Huynh, Steven

    2014-01-01

    Salmonella enterica has the ability to form biofilms and large aggregates on produce surfaces, including on cilantro leaves. Aggregates of S. enterica serovar Thompson that remained attached to cilantro leaves after rigorous washing and that were present free or bound to dislodged leaf tissue in the wash suspension were observed by confocal microscopy. Measurement of S. Thompson population sizes in the leaf washes by plate counts failed to show an effect of 0.05% Tween 80 on the removal of th...

  17. The materials science of protein aggregation

    OpenAIRE

    Cox, D L; Lashuel, H. A.; Lee, K. Y. C.; Singh, R. R. R.

    2005-01-01

    Numerous human diseases are associated with conformational change and aggregation of proteins, including Alzheimer's, Parkinson's, prion diseases (such as mad cow disease), familial amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), Huntington's, and type II (mature onset) diabetes. In many cases, it has been demonstrated that conformational change and aggregation can occur outside living cells and complex biochemical networks. Hence, approaches from materials and physical science ...

  18. Beyond the mucus escalator: Complex ciliary hydrodynamics in disease and function

    Science.gov (United States)

    Nawroth, Janna; Guo, Hanliang; John, Dabiri; Kanso, Eva; McFall-Ngai, Margaret

    2015-11-01

    Cilia are microscopic, hair-like structures lining external and internal body surfaces where they interact with fluids. The main function of motile cilia is often described as that of a ``mucus escalator'', i.e., a homogeneous ciliary carpet moving along layer of mucus along the surface to transport food, germ cells, debris, or pathogens. Accordingly, the performance of ciliary systems is usually measured in terms of a single metric, transport velocity, or its presumed proxy, ciliary beat frequency. We challenge this simple view through the observation that both healthy and diseased biological systems exhibit a variety of cilia morphologies, beat patterns, and arrangements, resulting in complex flow patterns and transport phenomena that cannot be reduced to a single parameter. Here we present two case studies. In one system, the ciliated surface creates two distinct flow regimes for first trapping and then sheltering potential symbiont bacteria for further biochemical screening. In the other system, chronic disease induces a misalignment of ciliary beat, leading to a pathological transition from uniform mucus transport to a pattern of stagnation and circulation. These studies suggest that (a), we need to develop a wider range of metrics for describing ciliary transport in biological and clinical contexts, and (b), engineered ciliated systems exploiting a variety of design parameters could provide novel ways of manipulating fluids at the microscale.

  19. A polymer physics perspective on driving forces and mechanisms for protein aggregation

    OpenAIRE

    Pappu, Rohit V.; Wang, Xiaoling; Vitalis, Andreas; Crick, Scott L.

    2007-01-01

    Protein aggregation is a commonly occurring problem in biology. Cells have evolved stress-response mechanisms to cope with problems posed by protein aggregation. Yet, these quality control mechanisms are overwhelmed by chronic aggregation-related stress and the resultant consequences of aggregation become toxic to cells. As a result, a variety of systemic and neurodegenerative diseases are associated with various aspects of protein aggregation and rational approaches to either inhibit aggrega...

  20. Charged Dust Aggregate Interactions

    Science.gov (United States)

    Matthews, Lorin; Hyde, Truell

    2015-11-01

    A proper understanding of the behavior of dust particle aggregates immersed in a complex plasma first requires a knowledge of the basic properties of the system. Among the most important of these are the net electrostatic charge and higher multipole moments on the dust aggregate as well as the manner in which the aggregate interacts with the local electrostatic fields. The formation of elongated, fractal-like aggregates levitating in the sheath electric field of a weakly ionized RF generated plasma discharge has recently been observed experimentally. The resulting data has shown that as aggregates approach one another, they can both accelerate and rotate. At equilibrium, aggregates are observed to levitate with regular spacing, rotating about their long axis aligned parallel to the sheath electric field. Since gas drag tends to slow any such rotation, energy must be constantly fed into the system in order to sustain it. A numerical model designed to analyze this motion provides both the electrostatic charge and higher multipole moments of the aggregate while including the forces due to thermophoresis, neutral gas drag, and the ion wakefield. This model will be used to investigate the ambient conditions leading to the observed interactions. This research is funded by NSF Grant 1414523.

  1. Aggregated Computational Toxicology Online Resource

    Data.gov (United States)

    U.S. Environmental Protection Agency — Aggregated Computational Toxicology Online Resource (AcTOR) is EPA's online aggregator of all the public sources of chemical toxicity data. ACToR aggregates data...

  2. Escalation of cocaine intake with extended access in rats: dysregulated addiction or regulated acquisition?

    Science.gov (United States)

    Beckmann, JS; Gipson, CD; Marusich, JA; Bardo, MT

    2013-01-01

    Rationale Understanding the neurobehavioral mechanisms underlying dysregulated cocaine intake is important for the development of new cocaine-abuse therapies. Objectives The current study determined if cocaine escalation under extended access conditions (6-hr access) is regulated by discrimination learning processes. Methods Rats were initially trained on cocaine self-administration (0.1 or 0.25 mg/kg/infusion) using a fixed ratio 1 (FR 1) schedule under 1-hr access for 12 sessions. Some rats were then trained to self-administer cocaine under 1-hr or 6-hr access conditions exclusively for an additional 14 sessions, while other rats were trained under both 1- and 6-hr access conditions that were cued or noncued for an additional 28 sessions (14 sessions for 1- and 6-hr access). Two additional groups of rats were initially trained to self-administer cocaine using an FR 1 schedule under 10-min access for 12 sessions; half of the animals were then switched to 60-min access conditions for an additional 14 sessions. Results When access conditions were differentially cued, escalation of cocaine intake was evident in animals with both 1- and 6-hr access during the escalation phase. Escalation also was evident in animals initially trained with 10-min access and then switched to 60-min access. Conclusions The results demonstrate that dysregulated and regulated intake can be expressed within the same animal, indicating that escalation is context-dependent. Furthermore, escalated cocaine intake can be expressed under 1-hr access conditions. Overall, these results suggest that escalated cocaine intake may be representative of a discrimination-dependent regulated intake process, rather than addiction-like, compulsive intake. PMID:22249361

  3. Increased cytoplasm viscosity hampers aggregate polar segregation in Escherichia coli.

    Science.gov (United States)

    Oliveira, Samuel M D; Neeli-Venkata, Ramakanth; Goncalves, Nadia S M; Santinha, João A; Martins, Leonardo; Tran, Huy; Mäkelä, Jarno; Gupta, Abhishekh; Barandas, Marilia; Häkkinen, Antti; Lloyd-Price, Jason; Fonseca, José M; Ribeiro, Andre S

    2016-02-01

    In Escherichia coli, under optimal conditions, protein aggregates associated with cellular aging are excluded from midcell by the nucleoid. We study the functionality of this process under sub-optimal temperatures from population and time lapse images of individual cells and aggregates and nucleoids within. We show that, as temperature decreases, aggregates become homogeneously distributed and uncorrelated with nucleoid size and location. We present evidence that this is due to increased cytoplasm viscosity, which weakens the anisotropy in aggregate displacements at the nucleoid borders that is responsible for their preference for polar localisation. Next, we show that in plasmolysed cells, which have increased cytoplasm viscosity, aggregates are also not preferentially located at the poles. Finally, we show that the inability of cells with increased viscosity to exclude aggregates from midcell results in enhanced aggregate concentration in between the nucleoids in cells close to dividing. This weakens the asymmetries in aggregate numbers between sister cells of subsequent generations required for rejuvenating cell lineages. We conclude that the process of exclusion of protein aggregates from midcell is not immune to stress conditions affecting the cytoplasm viscosity. The findings contribute to our understanding of E. coli's internal organisation and functioning, and its fragility to stressful conditions. PMID:26507787

  4. Protein Colloidal Aggregation Project

    Science.gov (United States)

    Oliva-Buisson, Yvette J. (Compiler)

    2014-01-01

    To investigate the pathways and kinetics of protein aggregation to allow accurate predictive modeling of the process and evaluation of potential inhibitors to prevalent diseases including cataract formation, chronic traumatic encephalopathy, Alzheimer's Disease, Parkinson's Disease and others.

  5. Platelet activation and aggregation

    DEFF Research Database (Denmark)

    Jensen, Maria Sander; Larsen, O H; Christiansen, Kirsten; Fenger-Eriksen, C; Ingerslev, J; Sørensen, Benny

    2013-01-01

    This study introduces a new laboratory model of whole blood platelet aggregation stimulated by endogenously generated thrombin, and explores this aspect in haemophilia A in which impaired thrombin generation is a major hallmark. The method was established to measure platelet aggregation initiated...... by tissue factor evaluated by means of impedance aggregometry. Citrated whole blood from healthy volunteers and haemophilia A patients with the addition of inhibitors of the contact pathway and fibrin polymerization was evaluated. In healthy persons, a second wave of platelet aggregation was found to...... coincide with the thrombin burst and to be abolished by thrombin inhibitors. In this system, platelet aggregation in severe haemophilia A (n = 10) was found to be significantly decreased as compared with healthy individuals (912 ± 294 vs. 1917 ± 793 AU × min, P = 0.003), most probably due to the weak level...

  6. Recycled aggregates concrete: aggregate and mix properties

    Directory of Open Access Journals (Sweden)

    González-Fonteboa, B.

    2005-09-01

    Full Text Available This study of structural concrete made with recycled concrete aggregate focuses on two issues: 1. The characterization of such aggregate on the Spanish market. This involved conducting standard tests to determine density, water absorption, grading, shape, flakiness and hardness. The results obtained show that, despite the considerable differences with respect to density and water absorption between these and natural aggregates, on the whole recycled aggregate is apt for use in concrete production. 2. Testing to determine the values of basic concrete properties: mix design parameters were established for structural concrete in non-aggressive environments. These parameters were used to produce conventional concrete, and then adjusted to manufacture recycled concrete aggregate (RCA concrete, in which 50% of the coarse aggregate was replaced by the recycled material. Tests were conducted to determine the physical (density of the fresh and hardened material, water absorption and mechanical (compressive strength, splitting tensile strength and modulus of elasticity properties. The results showed that, from the standpoint of its physical and mechanical properties, concrete in which RCA accounted for 50% of the coarse aggregate compared favourably to conventional concrete.

    Se aborda el estudio de hormigones estructurales fabricados con áridos reciclados procedentes de hormigón, incidiéndose en dos aspectos: 1. Caracterización de tales áridos, procedentes del mercado español. Para ello se llevan a cabo ensayos de densidad, absorción, granulometría, coeficiente de forma, índice de lajas y dureza. Los resultados obtenidos han puesto de manifiesto que, a pesar de que existen diferencias notables (sobre todo en cuanto a densidad y absorción con los áridos naturales, las características de los áridos hacen posible la fabricación de hormigones. 2. Ensayos sobre propiedades básicas de los hormigones: se establecen parámetros de dosificaci

  7. Coagulation with limited aggregations

    CERN Document Server

    Bertoin, Jean

    2012-01-01

    Smoluchowski's coagulation equations can be used as elementary mathematical models for the formation of polymers. We review here some recent contributions on a variation of this model in which the number of aggregations for each atom is a priori limited. Macroscopic results in the deterministic setting can be explained at the microscopic level by considering a version of stochastic coalescence with limited aggregations, which can be related to the so-called random configuration model of random graph theory.

  8. The Aggregation Dilemma

    OpenAIRE

    Ingmar Schumacher

    2014-01-01

    The results in this paper show that the level of aggregation used in a social welfare func- tion matters significantly for policy analysis. Using climate change as an example, it is shown that, under the mild and widely-accepted assumptions of asymmetric climate change impacts and declining marginal utility, an aggregation dilemma may arise that dwarfs most other policy-relevant aspects in the climate change cost-benefit analysis. Estimates based on the RICE-99 model (Nordhaus and Boyer 2000)...

  9. Report on waste burial charges: Escalation of decommissioning waste disposal costs at low-level waste burial facilities

    International Nuclear Information System (INIS)

    One of the requirements placed upon nuclear power reactor licensees by the US Nuclear Regulatory Commission (NRC) is for the licensees to periodically adjust the estimate of the cost of decommissioning their plant, in dollars of the current year, as part of the process to provide reasonable assurance that adequate funds for decommissioning will be available when needed. This report, which is scheduled to be revised annually, contains the development of a formula for escalating decommissioning cost estimates that is acceptable to the NRC, and contains values for the escalation of radioactive waste burial costs, by site and by year. The licensees may use the formula, the coefficients, and the burial escalation factors from this report in their escalation analysis, or may use an escalation rate at least equal to the escalation approach presented herein. 4 refs., 2 tabs

  10. From headache to tumour: An examination of health anxiety, health-related Internet use and 'query escalation'.

    Science.gov (United States)

    Singh, Karmpaul; Brown, Richard J

    2016-09-01

    The current study aimed to explore the phenomenon of disease-related 'query escalation' in high/low health anxious Internet users (N = 40). During a 15-minute health-related Internet search, participants rated their anxiety and the perceived seriousness of information on each page. Post-search interviews determined the reasons for, and effects of, escalating queries to consider serious diseases. Both groups were found to be significantly more anxious after escalating queries. The high group was significantly more likely to escalate queries. Evaluating personal relevance of material was the main reason for escalations and moderated anxiety post-escalation. We conclude that searching for online disease information can increase anxiety, particularly for people worried about their health. PMID:25706333

  11. Implementation of a combined Cardiopulmonary Resuscitation and Treatment Escalation Plan document in a District General Hospital.

    Science.gov (United States)

    Stockdale, Claire; Trivedi, Bhavi; Jerome, Ellen; Salih, Samir; Huntley, Christopher; Cooke, Eleanor; Massey, Yolanda; Mella, Sophie

    2014-01-01

    Documentation of appropriate escalation of treatment was identified as a problem for junior doctors and Critical Care Outreach Nurses at Musgrove Park Hospital. An audit of resuscitation and escalation documentation of all wards found that of the patients who were not for Cardiopulmonary resuscitation (and therefore not for full escalation of care), 78.4% had no documentation of the appropriate level of escalation of treatment should they deteriorate. The majority of junior doctors had experienced cases where they felt that inappropriate treatment had been given, where no escalation plan was documented. Using several Plan, Do, Study, Act (PDSA) cycles, drawing tools used in other trusts and departments, and the views of clinicians, we developed a treatment escalation plan (TEP) tool, to be included in the resuscitation form. This included consideration of referral to critical care, ward based non-invasive ventilation, and appropriate use of intravenous or oral antibiotics. This then prompted the responsible clinician to consider and document appropriate escalation of treatment. The CPR-TEP form was trialed using a quasi-experiment design allowing the aim to be tested using two groups - intervention and control. All patients in the intervention group were not for CPR and therefore had their TEP-CPR form filled in fully (n=68). The control group consisted of patients who were not for CPR but who did not have a TEP form filled in (n=36). The appropriateness of OOH (out of hours) treatment in those patients who experienced clinical deterioration was judged by questionnaire-based feedback from the in-hours team the following morning. Levels of inappropriate treatment between the two groups were compared to test the aim. At the end of the study period, questionnaire feedback indicated that 11.1% of patients in the group with the new CPR-TEP document had received inappropriate OOH care compared to 44.4% of patients in the group without the document. Using the TEP

  12. Modeling, simulation and analysis of group trampling risks during escalator transfers

    Science.gov (United States)

    Li, Wenhang; Gong, Jianhua; Yu, Ping; Shen, Shen

    2016-02-01

    The risks of group trampling during escalator transfers were studied in this paper. A state shifting model was proposed to describe the behaviors of a pedestrian during a group trampling accident. Based on the model, a group trample during escalator transfers was simulated from the beginning of the accident to the transfer recovery using the social force model. The impacts of 6 key factors were studied including the initial location of the accident, the time taken to invoke emergency measures, pedestrian velocity, escalator velocity, time taken for a fallen pedestrian to stand up, and pedestrian traffic. The results show that (1) when an accident happens in the transfer aisle, the peak number of pinned pedestrians is higher, while when it occurs near an escalator exit, the pressure exerted on the pinned pedestrians is more serious; (2) the speed of propagation of the accident is always faster than the recovery rate, and the earlier the emergency measures are taken, the less serious the accident is; (3) overall, except for the initial location of a trampling accident, which cannot be controlled, the other five factors have positive correlations with the severity of a group trampling accident, and can be descending ordered by their impacts using a regression analysis: early measures, pedestrian traffic, short standing-up delay, pedestrian velocity, and escalator velocity. These results can be referenced in the development of countermeasures to reduce group trampling risks.

  13. A systematic methodology review of phase I radiation dose escalation trials

    International Nuclear Information System (INIS)

    Background and purpose: The purpose of this review is to evaluate the methodology used in published phase I radiotherapy (RT) dose escalation trials. A specific emphasis was placed on the frequency of reporting late complications as endpoint. Materials and methods: We performed a systematic literature review using a predefined search strategy to identify all phase I trials reporting on external radiotherapy dose escalation in cancer patients. Results: Fifty-three trials (phase I: n = 36, phase I-II: n = 17) fulfilled the inclusion criteria. Of these, 20 used a modified Fibonacci design for the RT dose escalation, but 32 did not specify a design. Late toxicity was variously defined as >3 months (n = 43) or > 6 months (n = 3) after RT, or not defined (n = 7). In only nine studies the maximum tolerated dose (MTD) was related to late toxicity, while only half the studies reported the minimum follow-up period for dose escalation (n = 26). Conclusion: In phase I RT trials, late complications are often not taken into account and there is currently no consensus on the methodology used for radiation dose escalation studies. We therefore propose a decision-tree algorithm which depends on the endpoint selected and whether a validated early surrogate endpoint is available, in order to choose the most appropriate study design.

  14. Aggregate National Early Warning Score (NEWS) values are more important than high scores for a single vital signs parameter for discriminating the risk of adverse outcomes

    OpenAIRE

    Jarvis, Stuart; Kovacs, Caroline; Briggs, Jim; Meredith, Paul; Schmidt, Paul E.; Featherstone, Peter I.; Prytherch, David; Smith, Gary B.

    2015-01-01

    Introduction The Royal College of Physicians (RCPL) National Early Warning Score (NEWS) escalates care to a doctor at NEWS values of ≥5 and when the score for any single vital sign is 3. Methods We calculated the 24-h risk of serious clinical outcomes for vital signs observation sets with NEWS values of 3, 4 and 5, separately determining risks when the score did/did not include a single score of 3. We compared workloads generated by the RCPL's escalation protocol and for aggregate NEWS value ...

  15. Revisiting the cost escalation curse of nuclear power. New lessons from the French experience

    International Nuclear Information System (INIS)

    Since the first wave of nuclear reactors in 1970 to the construction of Generation III+ reactors in Finland and France in 2005 and 2007 respectively, nuclear power seems to be doomed to a cost escalation curse. In this paper we reexamine this issue for the French nuclear power fleet. Using the construction costs from the Cour des Comptes report, that was publicly available in 2012, we found that previous studies overestimated the cost escalation. Although, it is undeniable that the scale-up ended up in more costly reactors, we found evidence of a learning curve within the same size and type of reactors. This result confirms that standardization is a good direction to look, in order to overcome the cost escalation curse. (authors)

  16. Audience reactions to peace journalism: How supporters and critics of the Israeli policy process escalation and de-escalation oriented media frames

    Directory of Open Access Journals (Sweden)

    Stephanie Thiel

    2014-04-01

    Full Text Available This paper reports on an experiment that uses the Israeli-Palestinian conflict as a natural laboratory for studying how recipients make sense of escalation vs. de-escalation oriented news articles. The results of the study indicate that media frames and individual frames have both a direct effect and complex interaction effects on participants’ text understanding. Particularly the effect of media war frames diminishes if they are incongruent with participants’ individual frames, and the propaganda function of reports about violence and human casualties can be neutralized if framed according to a peace frame. If participants had a priori positioned themselves in favor of the perpetrator, they may produce reactance, however.

  17. Verbal De-escalation of the Agitated Patient: Consensus Statement of the American Association for Emergency Psychiatry Project BETA De-escalation Workgroup

    Directory of Open Access Journals (Sweden)

    Janet S. Richmond

    2012-04-01

    Full Text Available Agitation is an acute behavioral emergency requiring immediate intervention. Traditional methods of treating agitated patients, ie, routine restraints and involuntary medication, have been replaced with a much greater emphasis on a noncoercive approach. Experienced practitioners have found that if such interventions are undertaken with genuine commitment, successful outcomes can occur far more often than previously thought possible. In the new paradigm, a 3-step approach is used. First, the patient is verbally engaged; then a collaborative relationship is established; and, finally, the patient is verbally deescalated out of the agitated state. Verbal de-escalation is usually the key to engaging the patient and helping him become an active partner in his evaluation and treatment; although, we also recognize that in some cases nonverbal approaches, such as voluntary medication and environment planning, are also important. When working with an agitated patient, there are 4 main objectives: (1 ensure the safety of the patient, staff, and others in the area; (2 help the patient manage his emotions and distress and maintain or regain control of his behavior; (3 avoid the use of restraint when at all possible; and (4 avoid coercive interventions that escalate agitation. The authors detail the proper foundations for appropriate training for de-escalation and provide intervention guidelines, using the ‘‘10 domains of deescalation.’’ [West J Emerg Med. 2012;13(1:17–25.

  18. A Multi-dimensional Analysis of the Escalation of the Syrian Conflict

    OpenAIRE

    Hassaniyan, Allan; khalili, alireza; Huynh, My Phung; Daubner, Lukas

    2014-01-01

    The purpose of this project is to examine the escalation of the ongoing conflict in Syria, which began in 2011. It started with a peaceful protest against the Assad regime, after it developed into a bloody civil war within one year. To get an understanding to the question why the situation escalates in the way it did, there will be an analysis of three main factors: the ethnic and religious division of the Syrian society, the relationship between Syrians and its government framed as a (pathol...

  19. Role of Carbonyl Modifications on Aging-Associated Protein Aggregation

    Science.gov (United States)

    Tanase, Maya; Urbanska, Aleksandra M.; Zolla, Valerio; Clement, Cristina C.; Huang, Liling; Morozova, Kateryna; Follo, Carlo; Goldberg, Michael; Roda, Barbara; Reschiglian, Pierluigi; Santambrogio, Laura

    2016-01-01

    Protein aggregation is a common biological phenomenon, observed in different physiological and pathological conditions. Decreased protein solubility and a tendency to aggregate is also observed during physiological aging but the causes are currently unknown. Herein we performed a biophysical separation of aging-related high molecular weight aggregates, isolated from the bone marrow and splenic cells of aging mice and followed by biochemical and mass spectrometric analysis. The analysis indicated that compared to younger mice an increase in protein post-translational carbonylation was observed. The causative role of these modifications in inducing protein misfolding and aggregation was determined by inducing carbonyl stress in young mice, which recapitulated the increased protein aggregation observed in old mice. Altogether our analysis indicates that oxidative stress-related post-translational modifications accumulate in the aging proteome and are responsible for increased protein aggregation and altered cell proteostasis.

  20. Sustainable Concrete with Recycled Aggregate

    OpenAIRE

    Kara, P

    2012-01-01

    Concretes produced with recycled aggregates are the subject of several papers recently published in the technical literature. Substitution of natural aggregates can be one of possibilities to take care of landfills and increase of CO2 emissions into the atmosphere in Latvia. Recycled aggregate is a valuable resource; value-added consumption of recycled aggregate, as replacement for virgin aggregate in concrete, can yield significant energy and environmental benefits. In present study recycled...

  1. Arrow's Theorem in Judgement Aggregation

    OpenAIRE

    Franz Dietrich; Christian List

    2005-01-01

    In response to recent work on the aggregation of individual judgements on logically connected propositions into collective judgements, it is often asked whether judgement aggregation is a special case of Arrowian preference aggregation. We argue the opposite. After proving a general impossibility theorem, we construct an embedding of preference aggregation into judgement aggregation and prove Arrow's theorem as a corollary of our result. Although we provide a new proof of Arrow's theorem, our...

  2. Absorption Spectra of Astaxanthin Aggregates

    OpenAIRE

    Olsina, Jan; Durchan, Milan; Minofar, Babak; Polivka, Tomas; Mancal, Tomas

    2012-01-01

    Carotenoids in hydrated polar solvents form aggregates characterized by dramatic changes in their absorption spectra with respect to monomers. Here we analyze absorption spectra of aggregates of the carotenoid astaxanthin in hydrated dimethylsulfoxide. Depending on water content, two types of aggregates were produced: H-aggregates with absorption maximum around 390 nm, and J-aggregates with red-shifted absorption band peaking at wavelengths >550 nm. The large shifts with respect to absorption...

  3. Aggregate Oligopoly Games with Entry

    OpenAIRE

    Anderson, Simon P.; Erkal, Nisvan; Piccinin, Daniel

    2013-01-01

    We use cumulative reaction functions to compare long-run market structures in aggregative oligopoly games. We first compile an IO toolkit for aggregative games. We show strong neutrality properties across market structures. The aggregator stays the same, despite changes in the number of firms and their actions. The IIA property of demands (CES and logit) implies that consumer surplus depends on the aggregator alone, and that the Bertrand pricing game is aggregative. We link together the follo...

  4. Modeling the Aggregation Propensity and Toxicity of Amyloid-β Variants

    DEFF Research Database (Denmark)

    Tiwari, Manish Kumar; Kepp, Kasper Planeta

    2015-01-01

    contributes to our understanding of amyloid aggregation and suggests a method to predict aggregation propensity and toxicity of Aβ variants, and potentially to reduce aggregation propensities of amyloids by molecular intervention directed toward specific conformations of the peptides........ The present paper reports modeling of the aggregation propensities and cell toxicities of genetic variants of Aβ known to increase disease risk. From correlation to experimental data, and using four distinct experimental structures to test structural sensitivity, we find that the Spatial Aggregation...

  5. Growth hormone aggregates in the rat adenohypophysis

    Science.gov (United States)

    Farrington, M.; Hymer, W. C.

    1990-01-01

    Although it has been known for some time that GH aggregates are contained within the rat anterior pituitary gland, the role that they might play in pituitary function is unknown. The present study examines this issue using the technique of Western blotting, which permitted visualization of 11 GH variants with apparent mol wt ranging from 14-88K. Electroelution of the higher mol wt variants from gels followed by their chemical reduction with beta-mercaptoethanol increased GH immunoassayability by about 5-fold. With the blot procedure we found 1) that GH aggregates greater than 44K were associated with a 40,000 x g sedimentable fraction; 2) that GH aggregates were not present in glands from thyroidectomized rats, but were in glands from the thyroidectomized rats injected with T4; 3) that GH aggregates were uniquely associated with a heavily granulated somatotroph subpopulation isolated by density gradient centrifugation; and 4) that high mol wt GH forms were released from the dense somatotrophs in culture, since treatment of the culture medium with beta-mercaptoethanol increased GH immunoassayability by about 5-fold. Taken together, the results show that high mol wt GH aggregates are contained in secretory granules of certain somatotrophs and are also released in aggregate form from these cells in vitro.

  6. Dielectric modelling of erythrocyte aggregation in blood

    International Nuclear Information System (INIS)

    The dielectric spectrum of whole blood is markedly changed by aggregation of erythrocytes, the so-called rouleau formation. The dielectric behaviour has been simulated using an erythrocyte model that is a disc covered with a thin membrane and an erythrocyte aggregate model that is a pile of the discs with regular spacing ds. The effective complex permittivity of a cubic system including one of the models was calculated by a numerical technique based on the three-dimensional finite-difference method. Both the models have anisotropic dielectric properties depending on whether the rotational axis of the separate or the aggregate model is parallel (the parallel orientation) or perpendicular (the perpendicular orientation) to the direction of the applied electric field. The models both showed a single dielectric relaxation, which was different in intensity and characteristic frequency between the two orientations. For the erythrocyte aggregate model, the relaxation intensity Δε increased and the characteristic frequency fc decreased with decreasing ds in the perpendicular orientation, whereas the opposite ds-dependence was found for Δε and fc in the parallel orientation. Increasing the number of cells in the aggregate model enhanced these effects. The difference in dielectric spectrum between the separate and the aggregate models represented well the dielectric spectrum change caused by rouleau formation

  7. Detection of ubiquitinated huntingtin species in intracellular aggregates

    Directory of Open Access Journals (Sweden)

    Katrin eJuenemann

    2015-01-01

    Full Text Available Protein conformation diseases, including polyglutamine diseases, result from the accumulation and aggregation of misfolded proteins. Huntington’s disease is one of nine diseases caused by an expanded polyglutamine repeat within the affected protein and is hallmarked by intracellular inclusion bodies composed of aggregated N-terminal huntingtin fragments and other sequestered proteins. Fluorescence microscopy and filter trap assay are conventional methods to study protein aggregates, but cannot be used to analyze the presence and levels of post-translational modifications of aggregated huntingtin such as ubiquitination. Ubiquitination of proteins can be a signal for degradation and intracellular localization, but also affects protein activity and protein-protein interactions. The function of ubiquitination relies on its mono- and polymeric isoforms attached to protein substrates. Studying the ubiquitination pattern of aggregated huntingtin fragments offers an important possibility to understand huntingtin degradation and aggregation processes within the cell. For the identification of aggregated huntingtin and its ubiquitinated species, solubilization of the cellular aggregates is mandatory. Here we describe methods to identify post-translational modifications such as ubiquitination of aggregated mutant huntingtin. This approach is specifically described for use with mammalian cell culture and is suitable to study other disease-related proteins prone to aggregate.

  8. N-Acetylcysteine potentiates inhibition of platelet aggregation by nitroglycerin.

    OpenAIRE

    Loscalzo, J

    1985-01-01

    Platelet aggregation is currently felt to play an important role in the pathogenesis of ischemic vascular disorders. The smooth muscle relaxant, nitroglycerin, has been shown to inhibit platelet aggregation in vitro, but at concentrations that were felt to be unattainable in vivo. Because the in vivo action of nitroglycerin on smooth muscle cells has been shown to depend on the presence of reduced cytosolic sulfhydryl groups, the inhibitory effect of nitroglycerin on platelet aggregation was ...

  9. Effects of ultraviolet radiation on aggregation of human erythrocytes

    International Nuclear Information System (INIS)

    Aggregation of erythrocytes induced by Alcian blue is increased under small UV-irradiation doses. Rouleaux formation in dextran solution remained unchanged. Under UV-irradiation blood plasma acquires a greater ability to induce rouleaux formation of native cells. This is, apparently, due to protein aggregates formed in plasma. Erythrocytes irradiated by high dose lose the aggregation ability in the presence of Alcian blue. The effect is enhanced postirradiation, its base is peroxidation of membrane lipids. (orig.)

  10. Effects of ultraviolet radiation on aggregation of human erythrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Murina, M.A.; Roshchupkin, D.I. (2nd Moscow Medical Institute, Moscow (USSR). Dept. of Biophysics)

    1984-01-01

    Aggregation of erythrocytes induced by Alcian blue is increased under small UV-irradiation doses. Rouleaux formation in dextran solution remained unchanged. Under UV-irradiation blood plasma acquires a greater ability to induce rouleaux formation of native cells. This is, apparently, due to protein aggregates formed in plasma. Erythrocytes irradiated by high dose lose the aggregation ability in the presence of Alcian blue. The effect is enhanced postirradiation, its base is peroxidation of membrane lipids.

  11. Aggregation on heterogeneous surface

    Institute of Scientific and Technical Information of China (English)

    Lu Hang-Jun; Wu Feng-Min; Fang Yun-Zhang

    2004-01-01

    Chessboard-like substrates are introduced in this paper, in order to study the diffusion-limited aggregation (DLA)and the motion of poly-atoms on heterogeneous surfaces. The effect of morphology of such substrates upon the cluster aggregation is investigated using the Monte Carlo simulation. It is found that the growth process and the cluster morphology are governed by the energetic topography of the substrates. Our simulation also indicate that the island density and the fractal dimension of the clusters depend strongly on the substrate topography and the activation energy.

  12. Report on waste burial charges: Escalation of decommissioning waste disposal costs at low-level waste burial facilities

    International Nuclear Information System (INIS)

    One of the requirements placed upon nuclear power reactor licensees by the US Nuclear Regulatory Commission (NRC) is for the licensees to periodically adjust the estimate of the cost of decommissioning their plant, in dollars of the current year, as part of the process to provide reasonable assurance that adequate funds for decommissioning will be available when added. This report, which is scheduled to be revised annually, contains the development of a formula for escalating decommissioning cost estimates that is acceptable to the NRC. The sources of information to be used in the escalation formula are identified, and the values developed for the escalation of radioactive waste burial costs, by site and by year, are given in this report. The licensees may use the formula, the coefficients, and the burial escalation factors from this report in their escalation analysis, or may use an escalation rate at least equal to the escalation approach presented herein. The formula and its coefficients, together with guidance to the appropriate sources of data, are summarized in Chapter 2. The development of the formula and its coefficients are presented in Chapter 3. Price schedules for burial for the year of issue of this report are given in Appendix A, for currently operating burial sites. The calculations performed to determine the burial cost escalation factors, Bx, for each site for the year 1988 are summarized in Appendix B. 4 refs., 6 tabs

  13. Aggregates, broccoli and cauliflower

    Science.gov (United States)

    Grey, Francois; Kjems, Jørgen K.

    1989-09-01

    Naturally grown structures with fractal characters like broccoli and cauliflower are discussed and compared with DLA-type aggregates. It is suggested that the branching density can be used to characterize the growth process and an experimental method to determine this parameter is proposed.

  14. Diffusion in aggregated soil.

    NARCIS (Netherlands)

    Rappoldt, C.

    1992-01-01

    The structure of an aggregated soil is characterized by the distribution of the distance from an arbitrary point in the soil to the nearest macropore or crack. From this distribution an equivalent model system is derived to which a diffusion model can be more easily applied. The model system consist

  15. Non-coplanar beam intensity modulation allows large dose escalation in stage III lung cancer

    International Nuclear Information System (INIS)

    Purpose: To evaluate the feasibility of dose escalation in stage III non-small cell lung cancer, we compared standard coplanar (2D) with non-coplanar beam arrangements, without (3D) and with beam intensity modulation (3D-BIM). Materials and methods: This study was a planning effort performed on a non-selected group of 10 patients. Starting from a serial CT scan, treatment planning was performed using Sherouse's GRATISTM 3D planning system. Two target volumes were defined; gross tumor volume (GTV) defined a high-dose target volume that had to receive a dose of at least 80 Gy and GTV plus the lymph node regions with >10% probability of invasion defined an intermediate-dose target volume (GTV+N). It was our intention to irradiate GTV+N up to 56 Gy or more. If the prescribed doses on GTV and GTV+N could not be reached with either the 2D or 3D technique, a 3D-BIM plan was performed. The 3D-BIM plan was a class solution involving identical gantry angles, segment arrangements and relative segment weights for all patients. Dose volume histograms for GTV, GTV+N, lung and spinal cord were calculated. Criteria for tolerance were met if no points inside the spinal cord exceeded 50 Gy and if at least 50% of the lung volume received less than 20 Gy. Under these constraints, maximal achievable doses to GTV and GTV+N were calculated. Results: In all 2D plans, spinal cord was the limiting factor and the prescribed doses for GTV and GTV+N could not be reached in any patient. The non-coplanar 3D plan resulted in a satisfying solution in 4 out of 10 patients under the same constraints. In comparison with 2D, the minimum dose in GTV+N was increased. Six patients had to be planned with the 3D-BIM technique. The theoretical minimum dose to GTV+N ranged between 56 and 98 Gy. The delivery of 80 Gy or more to GTV was possible in all patients. For a minimal dose of 80 Gy to GTV, the maximal dose to any point of the spinal cord varied between 27 and 46 Gy. The lung volume receiving more than

  16. Escalation of Agitative Rhetoric: A Case Study of Mattachine Midwest, 1967-1970.

    Science.gov (United States)

    Darsey, James

    This paper examines the adequacy of Bowers and Ochs' theory of social movements as applied to the escalating agitative strategies of a dissident group, the homosexual-rights organization Mattachine Midwest. The group's activities are described chronologically, in terms of the strategies employed: petition, promulgation, polarization,…

  17. Silent Escalation: Salaries of Senior University Administrators in Ontario, 1996-2006

    Science.gov (United States)

    Essaji, Azim; Horton, Sue

    2010-01-01

    The real compensation of senior university administrators in Ontario has increased by over 43% in the last decade. The escalation is especially pronounced for presidents and provosts: their pay has risen by 63% in real terms between 1996 and 2006. These trends have been evident in universities of all types, for both genders and for professional as…

  18. Symptom Induction and De-escalation in the Treatment of Panic Attacks.

    Science.gov (United States)

    Dattilio, Frank M.

    1990-01-01

    Describes technique known as symptom induction and de-escalation for panic attacks in which goal is to reproduce the type of situation that may precipitate an attack and then to show the client how the attacks can be "turned on" as well as "turned off." (ABL)

  19. Some Take the Glass Escalator, Some Hit the Glass Ceiling? Career Consequences of Occupational Sex Segregation.

    Science.gov (United States)

    Hultin, Mia

    2003-01-01

    Analysis of Swedish longitudinal data (1,535 men, 1,584 women) showed that men in female-dominated occupations have substantially better internal promotion opportunities than equally qualified women. In male-dominated occupations, men and women have equal internal promotion chances. Results suggest a "glass escalator" advantage for men but not a…

  20. Compartment-specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition

    DEFF Research Database (Denmark)

    Miller, Stephanie Bm; Ho, Chi-Ting; Winkler, Juliane;

    2015-01-01

    Disruption of the functional protein balance in living cells activates protective quality control systems to repair damaged proteins or sequester potentially cytotoxic misfolded proteins into aggregates. The established model based on Saccharomyces cerevisiae indicates that aggregating proteins i...

  1. Radiation dose escalation for loco-regional recurrence of breast cancer after mastectomy

    International Nuclear Information System (INIS)

    Radiation is a standard component of treatment for patients with locoregional recurrence (LRR) of breast cancer following mastectomy. The current study reports the results of a 10% radiation dose escalation in these patients. 159 patients treated at MD Anderson Cancer Center between 1994-2006 with isolated LRR after mastectomy alone were reviewed. Patients in the standard treatment group (65 pts, 40.9%) were treated to 50 Gy comprehensively plus a boost of 10 Gy. The dose escalated group (94 pts, 59.1%) was treated to 54 Gy comprehensively and a minimum 12 Gy boost. Median dose in the standard dose and dose escalated group was 60 Gy (±1 Gy, 95% CI) and 66 Gy (±0.5 Gy, 95% CI) respectively. Median follow up for living patients was 94 months from time of recurrence. The actuarial five year locoregional control (LRC) rate was 77% for the entire study population. The five year overall survival and disease-free survival was 55% and 41%, respectively. On multivariate analysis, initial tumor size (p = 0.03), time to initial LRR (p = 0.03), absence of gross tumor at the time of radiation (p = 0.001) and Her2 status (p = 0.03) were associated with improved LRC. Five year LRC rates were similar in patients with a complete response to chemotherapy without surgery and patients with a complete surgical excision (77% vs 83%, p = NS), compared to a 63% LRC rate in patients with gross disease at the time of radiation (p = 0.024). LRC rates were 80% in the standard dose group and 75% in the dose escalated group (p = NS). While LRR following mastectomy is potentially curable, distant metastasis and local control rates remain suboptimal. Radiation dose escalation did not appear to improve LRC. Given significant local failure rates, these patients are good candidates for additional strategies to improve their outcomes

  2. Shaping the Growth Behaviour of Biofilms Initiated from Bacterial Aggregates.

    Science.gov (United States)

    Melaugh, Gavin; Hutchison, Jaime; Kragh, Kasper Nørskov; Irie, Yasuhiko; Roberts, Aled; Bjarnsholt, Thomas; Diggle, Stephen P; Gordon, Vernita D; Allen, Rosalind J

    2016-01-01

    Bacterial biofilms are usually assumed to originate from individual cells deposited on a surface. However, many biofilm-forming bacteria tend to aggregate in the planktonic phase so that it is possible that many natural and infectious biofilms originate wholly or partially from pre-formed cell aggregates. Here, we use agent-based computer simulations to investigate the role of pre-formed aggregates in biofilm development. Focusing on the initial shape the aggregate forms on the surface, we find that the degree of spreading of an aggregate on a surface can play an important role in determining its eventual fate during biofilm development. Specifically, initially spread aggregates perform better when competition with surrounding unaggregated bacterial cells is low, while initially rounded aggregates perform better when competition with surrounding unaggregated cells is high. These contrasting outcomes are governed by a trade-off between aggregate surface area and height. Our results provide new insight into biofilm formation and development, and reveal new factors that may be at play in the social evolution of biofilm communities. PMID:26934187

  3. Aggregation Algorithms in Heterogeneous Tables

    OpenAIRE

    Titus Felix FURTUNA; Ivan, Ion; Marian DARDALA

    2006-01-01

    The heterogeneous tables are most used in the problem of aggregation. A solution for this problem is to standardize these tables of figures. In this paper, we proposed some methods of aggregation based on the hierarchical algorithms.

  4. Phase 1 Dose- Escalation Trial of Clofarabine Followed by Escalating Dose of Fractionated Cyclophosphamide in Adults with Relapsed or Refractory Acute Leukaemias

    OpenAIRE

    Zeidan, Amer M.; Ricklis, Rebecca M.; Carraway, Hetty E.; Yun, Hyun D.; Greer, Jacqueline M.; Smith, B. Douglas; Levis, Mark J.; McDevitt, Michael A.; Pratz, Keith W.; Showel, Margaret M.; Gladstone, Douglas E; Gore, Steven D.; Judith E Karp

    2012-01-01

    The prognosis of patients with relapsed and refractory acute leukaemia (RRAL) is very poor. Forty patients with RRAL were enrolled (28 acute myeloid leukaemia [AML], 12 acute lymphoblastic leukaemia [ALL]) in this Phase 1 dose-escalation trial of daily-infused clofarabine (CLO) followed by cyclophosphamide (CY) for 4 consecutive days (CLO-CYx4). The median age was 48.5 years. The median number of prior regimens was 2 (range 1–5), and 6/40 patients (15%) had prior allogeneic haematopoietic ste...

  5. ASSESSMENT OF RECYCLED AGGREGATE CONCRETE

    OpenAIRE

    Ahmad Mujahid Ahmad Zaidi

    2009-01-01

    Used of recycled aggregate (RA) in concrete can be described in environmental protection and economical terms. The application of recycled aggregate to use in construction activities have been practice by developed European countries and also of some Asian countries. This paper reports the results of an experimental study on the mechanical properties of recycled aggregate concrete (RAC) as compared to natural aggregate concrete (NAC). The effects of size of RA on compressive strength were dis...

  6. Judgement aggregation and distributed thinking

    OpenAIRE

    Spiekermann, Kai

    2010-01-01

    In recent years, judgement aggregation has emerged as an important area of social choice theory. Judgement aggregation is concerned with aggregating sets of individual judgements over logically connected propositions into a set of collective judgements. It has been shown that even seemingly weak conditions on the aggregation function make it impossible to find functions that produce rational collective judgements from all possible rational individual judgements. This implies...

  7. Aggregating governance indicators

    OpenAIRE

    Kaufmann, Daniel; Kraay, Aart; Zoido-Lobaton, Pablo

    1999-01-01

    In recent years the growing interest of academics and policymakers in governance has been reflected in the proliferation of cross-country indices measuring various aspects of governance. The authors explain how a simple variant of an unobserved components model can be used to combine the information from these different sources into aggregate governance indicators. The main advantage of this method us that it allows quantification of the precision of both individual sources of governance data...

  8. Study of Recycled Concrete Aggregates

    OpenAIRE

    Jitender Sharma; Sandeep Singla

    2014-01-01

    This paper describes the introduction and production of recycled concrete aggregates and its various applications in the construction industry. In this paper, properties of recycled aggregates and its comparison with the natural aggregates are also mentioned. Future recommendations about RCA are also included.

  9. Proteins aggregation and human diseases

    Science.gov (United States)

    Hu, Chin-Kun

    2015-04-01

    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease.

  10. Lanosterol reverses protein aggregation in cataracts.

    Science.gov (United States)

    Zhao, Ling; Chen, Xiang-Jun; Zhu, Jie; Xi, Yi-Bo; Yang, Xu; Hu, Li-Dan; Ouyang, Hong; Patel, Sherrina H; Jin, Xin; Lin, Danni; Wu, Frances; Flagg, Ken; Cai, Huimin; Li, Gen; Cao, Guiqun; Lin, Ying; Chen, Daniel; Wen, Cindy; Chung, Christopher; Wang, Yandong; Qiu, Austin; Yeh, Emily; Wang, Wenqiu; Hu, Xun; Grob, Seanna; Abagyan, Ruben; Su, Zhiguang; Tjondro, Harry Christianto; Zhao, Xi-Juan; Luo, Hongrong; Hou, Rui; Perry, J Jefferson P; Gao, Weiwei; Kozak, Igor; Granet, David; Li, Yingrui; Sun, Xiaodong; Wang, Jun; Zhang, Liangfang; Liu, Yizhi; Yan, Yong-Bin; Zhang, Kang

    2015-07-30

    The human lens is comprised largely of crystallin proteins assembled into a highly ordered, interactive macro-structure essential for lens transparency and refractive index. Any disruption of intra- or inter-protein interactions will alter this delicate structure, exposing hydrophobic surfaces, with consequent protein aggregation and cataract formation. Cataracts are the most common cause of blindness worldwide, affecting tens of millions of people, and currently the only treatment is surgical removal of cataractous lenses. The precise mechanisms by which lens proteins both prevent aggregation and maintain lens transparency are largely unknown. Lanosterol is an amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. Here we identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Both of these mutations affect highly conserved amino acid residues and impair key catalytic functions of LSS. Engineered expression of wild-type, but not mutant, LSS prevents intracellular protein aggregation of various cataract-causing mutant crystallins. Treatment by lanosterol, but not cholesterol, significantly decreased preformed protein aggregates both in vitro and in cell-transfection experiments. We further show that lanosterol treatment could reduce cataract severity and increase transparency in dissected rabbit cataractous lenses in vitro and cataract severity in vivo in dogs. Our study identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment. PMID:26200341

  11. Evidence Why Paroxetine Dose Escalation is Not Effective in Major Depressive Disorder: A Randomized Controlled Trial With Assessment of Serotonin Transporter Occupancy

    NARCIS (Netherlands)

    H.G. Ruhé; J. Booij; H.C.V. Weert; J.B. Reitsma; E.J.F. Fransen; M.C. Michel; A.H. Schene

    2009-01-01

    Dose escalation is often used in depressed patients who fail to respond to standard doses of selective serotonin reuptake inhibitors, but clinical efficacy is equivocal. We aimed to reassess the efficacy of paroxetine dose escalation and quantify whether paroxetine dose escalation increases occupanc

  12. Antipsychotic dose escalation as a trigger for Neuroleptic Malignant Syndrome (NMS: literature review and case series report

    Directory of Open Access Journals (Sweden)

    Langan Julie

    2012-11-01

    Full Text Available Abstract Background “Neuroleptic malignant syndrome” (NMS is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifically defined. Description We aimed to identify cases of NMS and review risk factors for its development with a particular focus on rapid dose escalation in the 30 days prior to onset. A review of the literature on rapid dose escalation was undertaken and a pragmatic definition of “rapid dose escalation” was made. NMS cases were defined using DSM-IV criteria and systematically identified within a secondary care mental health service. A ratio of titration rate was calculated for each NMS patient and “rapid escalators” and “non rapid escalators” were compared. 13 cases of NMS were identified. A progressive mean dose increase 15 days prior to the confirmed episode of NMS was observed (241.7 mg/day during days 1–15 to 346.9 mg/day during days 16–30 and the mean ratio of dose escalation for NMS patients was 1.4. Rapid dose escalation was seen in 5/13 cases and non rapid escalators had markedly higher daily cumulative antipsychotic dose compared to rapid escalators. Conclusions Rapid dose escalation occurred in less than half of this case series (n = 5, 38.5%, although there is currently no consensus on the precise definition of rapid dose escalation. Cumulative antipsychotic dose – alongside other known risk factors - may also be important in the development of NMS.

  13. Developmental competence of porcine chimeric embryos produced by aggregation

    DEFF Research Database (Denmark)

    Li, Juan; Jakobsen, Jannik E.; Xiong, Qiang;

    2015-01-01

    either by parthenogenetic activation (PA) or handmade cloning (HMC). Results showed that the developmental competence of chimeric embryos, evaluated based on their blastocyst rate and total cell number per blastocyst, was increased when two whole 2-cell stage embryos (PA or HMC) were aggregated. In...... comparison, when two blastomeres were aggregated, the developmental competence of the chimeric embryos decreased if the blastomeres were either from PA or from HMC embryos, but not if they were from different sources, i.e. one PA and one HMC blastomere. To evaluate the cell contribution in embryo formation......The purpose of our study was to compare the developmental competence and blastomere allocation of porcine chimeric embryos formed by micro-well aggregation. Chimeras were created by aggregating either two blastomeres originating from 2-cell embryos or two whole embryos, where embryos were produced...

  14. Structure and aggregation in model tetramethylurea solutions

    International Nuclear Information System (INIS)

    The structure of model aqueous tetramethylurea (TMU) solutions is investigated employing large-scale (32 000, 64 000 particles) molecular dynamics simulations. Results are reported for TMU mole fractions, Xt, ranging from infinite dilution up to 0.07, and for two temperatures, 300 and 330 K. Two existing force fields for TMU-water solutions are considered. These are the GROMOS 53A6 united-atom TMU model combined with SPC/E water [TMU(GROMOS-UA)/W(SPC/E)], and the more frequently employed AMBER03 all-atom force field for TMU combined with the TIP3P water model [TMU(AMBER-AA)/W(TIP3P)]. It is shown that TMU has a tendency towards aggregation for both models considered, but the tendency is significantly stronger for the [TMU(AMBER-AA)/W(TIP3P)] force field. For this model signs of aggregation are detected at Xt = 0.005, aggregation is a well established feature of the solution at Xt = 0.02, and the aggregates increase further in size with increasing concentration. This is in agreement with at least some experimental studies, which report signals of aggregation in the low concentration regime. The TMU aggregates exhibit little structure and are simply loosely ordered, TMU-rich regions of solution. The [TMU(GROMOS-UA)/W(SPC/E)] model shows strong signs of aggregation only at higher concentrations (Xt ≳ 0.04), and the aggregates appear more loosely ordered, and less well-defined than those occurring in the [TMU(AMBER-AA)/W(TIP3P)] system. For both models, TMU aggregation increases when the temperature is increased from 300 to 330 K, consistent with an underlying entropy driven, hydrophobic interaction mechanism. At Xt = 0.07, the extra-molecular correlation length expected for microheterogeneous solutions has become comparable with the size of the simulation cell for both models considered, indicating that even the systems simulated here are sufficiently large only at low concentrations

  15. Absorption Spectra of Astaxanthin Aggregates

    CERN Document Server

    Olsina, Jan; Minofar, Babak; Polivka, Tomas; Mancal, Tomas

    2012-01-01

    Carotenoids in hydrated polar solvents form aggregates characterized by dramatic changes in their absorption spectra with respect to monomers. Here we analyze absorption spectra of aggregates of the carotenoid astaxanthin in hydrated dimethylsulfoxide. Depending on water content, two types of aggregates were produced: H-aggregates with absorption maximum around 390 nm, and J-aggregates with red-shifted absorption band peaking at wavelengths >550 nm. The large shifts with respect to absorption maximum of monomeric astaxanthin (470-495 nm depending on solvent) are caused by excitonic interaction between aggregated molecules. We applied molecular dynamics simulations to elucidate structure of astaxanthin dimer in water, and the resulting structure was used as a basis for calculations of absorption spectra. Absorption spectra of astaxanthin aggregates in hydrated dimethylsulfoxide were calculated using molecular exciton model with the resonance interaction energy between astaxanthin monomers constrained by semi-e...

  16. Two views of the comparative escalation of nuclear and coal-fired power plant costs

    International Nuclear Information System (INIS)

    Doan L. Phung critiques Charles Komanoff's 1981 book Power Plant Cost Escalation, which compares new nuclear plant costs unfavorably with those of new coal plants because of the increase in capital costs. Phung blames prophets of doom who ignore the escalating costs throughout the economy and now focus their anti-nuclear attacks in economic terms. Proposals by Alvin Weinberg and others to concentrate on reactor-safety improvements are used to conclude that these efforts will further expand the capital costs of nuclear plants and make them noncompetitive. Phung questions whether Komanoff's modeling considers enough of the political, regulatory, and technological factors to determine future costs. Komanoff replies by explaining his method of analysis and denying a bias against nuclear power. A postscript by Phung reiterates his criticism of simplistic calculations and extrapolations. 17 references

  17. Mitigation of fire damage and escalation by fireproofing: A risk-based strategy

    International Nuclear Information System (INIS)

    Passive fire protection by the application of fireproofing materials is a crucial safety barrier in the prevention of the escalation of fire scenarios. Fireproofing improves the capacity of process items and of support structures to maintain their structural integrity during a fire, preventing or at least delaying the collapse of structural elements. Maintenance and cost issues require, however, to apply such protection only where an actual risk of severe fire scenarios is present. Available methodologies for fireproofing application in on-shore installation do not consider the effect of jet-fires. In the present study, a risk-based methodology aimed at the protection from both pool fire and jet fire escalation was developed. The procedure addresses both the prevention of domino effect and the mitigation of asset damage due to the primary fire scenario. The method is mainly oriented to early design application, allowing the identification of fireproofing zones in the initial phases of lay-out definition.

  18. Aggregation and sinking behaviour of resuspended fluffy layer material

    Science.gov (United States)

    Ziervogel, Kai; Forster, Stefan

    2005-09-01

    The influence of pelagic diatom addition ( Skeletonema costatum) on aggregation dynamics of resuspended fluffy layer material containing natural microorganism assemblages (bacteria and pennate diatoms) was studied during two roller table experiments. Sediment samples were taken at a fine sand site (16 m water depth) located in Mecklenburg Bight, south-western Baltic Sea. Fluff was experimentally resuspended from sediment cores and aggregation processes with and without S. costatum were studied in rotating tanks. Total particulate matter was incorporated into artificial aggregates in equal shares after both roller table experiments. However, biogenic parameters (particulate organic carbon, particulate organic nitrogen, and carbohydrate equivalents), as well as cell numbers of bacteria and pennate diatoms were found in higher percentages in S. costatum aggregates compared to aggregates without S. costatum. Transparent exopolymer particles were apparently irrelevant in the aggregation process during both experiments. Settling velocities of S. costatum aggregates exceeding 1000 μm in diameter showed a significantly higher mean settling velocity compared to aggregates without S. costatum of the same size. The pronounced effect of pelagic diatoms on aggregation processes of fluff in terms of particle attributes, size, and therewith sinking velocities could be demonstrated and may lead to further insight into near bed particle transport in coastal waters.

  19. Intrapatient Dose Escalation of Anti–CTLA-4 Antibody in Patients With Metastatic Melanoma

    OpenAIRE

    Maker, Ajay V; Yang, James C.; Sherry, Richard M.; Topalian, Suzanne L.; Kammula, Udai S; Royal, Richard E.; Hughes, Marybeth; Yellin, Michael J.; Haworth, Leah R.; Levy, Catherine; Allen, Tamika; Mavroukakis, Sharon A.; Attia, Peter; Rosenberg, Steven A.

    2006-01-01

    We previously reported our experience in treating 56 patients with metastatic melanoma using a human anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody. Durable tumor regressions were seen that correlated with the induction of autoimmune toxicities. In this study, we treated 46 additional patients using an intrapatient dose escalation schema to test whether higher doses of anti–CTLA-4 antibody would induce increased autoimmunity and concomitant tumor regression. Twenty-three patients sta...

  20. The social process of escalation: a promising focus for crisis management research

    Directory of Open Access Journals (Sweden)

    Bergström Johan

    2012-06-01

    Full Text Available Abstract Background This study identifies a promising, new focus for the crisis management research in the health care domain. After reviewing the literature on health care crisis management, there seems to be a knowledge-gap regarding organisational change and adaption, especially when health care situations goes from normal, to non-normal, to pathological and further into a state of emergency or crisis. Discussion Based on studies of escalating situations in obstetric care it is suggested that two theoretical perspectives (contingency theory and the idea of failure as a result of incomplete interaction tend to simplify the issue of escalation rather than attend to its complexities (including the various power relations among the stakeholders involved. However studying the process of escalation as inherently complex and social allows us to see the definition of a situation as normal or non-normal as an exercise of power in itself, rather than representing a putatively correct response to a particular emergency. Implications The concept of escalation, when treated this way, can help us further the analysis of clinical and institutional acts and competence. It can also turn our attention to some important elements in a class of social phenomenon, crises and emergencies, that so far have not received the attention they deserve. Focusing on organisational choreography, that interplay of potential factors such as power, professional identity, organisational accountability, and experience, is not only a promising focus for future naturalistic research but also for developing more pragmatic strategies that can enhance organisational coordination and response in complex events.

  1. Team Coordination in Escalating Situations: An Empirical Study Using Mid-Fidelity Simulation

    OpenAIRE

    Bergström, Johan; Dahlström, Nicklas; Henriqson, Eder; Dekker, Sidney

    2010-01-01

    The performance of teams, with different levels of domain and crisis management experience, managing unexpected and escalating situations was observed using a mid-fidelity ship-bridge simulation and analysed by applying the central concepts of joint activity coordination as well as Woods’s theory building on data overload. The coordination strategies used by the teams were evaluated by applying coordination process indicators and the concept of control. The paper discusses how different aspect...

  2. Personal and Contextual Factors in the Escalation of Driving after Drinking Across the College Years

    OpenAIRE

    Quinn, Patrick D.; Fromme, Kim

    2012-01-01

    College students continue to drive after drinking at alarmingly high rates. Age trends suggest that driving after drinking increases from late adolescence across the college years, largely mirroring trends in binge drinking. Relatively little research, however, has examined change over time in driving after drinking among college students or tested whether some students might be at greater risk of escalations in driving after drinking. Using a sample of 1,833 non-abstaining students who compl...

  3. Use of pagers with an alarm escalation system to reduce cardiac monitor alarm signals.

    Science.gov (United States)

    Cvach, Maria M; Frank, Robert J; Doyle, Pete; Stevens, Zeina Khouri

    2014-01-01

    Alarm fatigue desensitizes nurses to alarm signals and presents potential for patient harm. This project describes an innovative method of communicating cardiac monitor alarms to pagers using an alarm escalation algorithm. This innovation was tested on 2 surgical progressive care units over a 6-month period. There was a significant decrease in mean frequency and duration of high-priority monitor alarms and improvement in nurses' perception of alarm response time, using this method of alarm communication. PMID:23963169

  4. Real Option Method and Escalation of Commitment in the Evaluation of Investment Projects

    OpenAIRE

    Mehrdad Karami; Farshid A. Farsani

    2011-01-01

    Problem statement: This study applies an experimental method to find out whether using the real option method along with the discounted cash flow techniques can reduce the decision-makers Escalation of Commitment (EC hereafter) or their desire to keep up their commitment to a failed project. Approach: The real option method used for the evaluation of long-term projects also measures the flexibility value which may be produced during the implementation of the project. Results: The results indi...

  5. Escalation of drug self-administration as a hallmark of persistent addiction liability

    OpenAIRE

    Edwards, Scott; Koob, George F.

    2013-01-01

    Drug addiction is a progressive, relapsing disease comprised of interlocking stages of disordered motivation. Numerous animal models describing various stages of the addiction process have been developed over the past few decades, providing considerable advantages for the modeling of drug addiction compared with other complex psychiatric disease states. Escalation of drug self-administration has emerged as a widely accepted operant conditioning model of excessive drug intake. We further argue...

  6. Escalated handling of young C57BL/6 mice results in altered Morris water maze performance

    OpenAIRE

    Fridgeirsdottir, Gudrun Andrea; Hillered, Lars; Clausen, Fredrik

    2014-01-01

    Background The handling of experimental animals prior to experimental interventions is often poorly described, even though it may affect the final functional outcome. This study explores how the use of repeated handling of C57BL/6 mice prior to Morris water maze (MWM) tests can affect the performance. Methods and materials The handled animals were subjected to the escalating handling protocol, with the investigator spending 5 min per day per cage for 8 days prior to the MWM test. On the last ...

  7. Familial aggregation of bladder cancer

    Directory of Open Access Journals (Sweden)

    Ilić Milena

    2011-01-01

    Full Text Available Background. Except for smoking and certain occupational exposures, the etiology of bladder cancer is largely unknown. Several case reports have described familial aggregation of transitional cell carcinoma of the bladder. Although the majority of patients with bladder cancer do not have family history of transitional cell carcinoma of the urinary tract, the study of familial transitional cell carcinoma may lead to the knowledge on the pathogenesis of this disease. The purpose of this study was to describe three cases of urinary bladder cancer in a single three-member family, i.e. in two generations (mother and son and a family member related by marriage (the patient’s wife. Case report. Three cases of urinary bladder cancer occurred in a three-member family within the interval of 5 years. The following common characteristics were detected in our patients: old age (over 60, working as farmers for more than 50 years, negative personal medical history on relevant health disorders, place of birth - village, place of residence - village, the same water supply, similar nutrition, positive family history on urinary bladder cancer or other malignant tumors, the first sign of illness was macroscopic hematuria in all the patients and the same pathohistological type of cancer - carcinoma papillare transitiocellulare. Conclusion. The stated common characteristics in our cases indicate, above all, the impact of exposure to external surrounding factors on the occurrence of urinary bladder cancer.

  8. Aggregate Demand and Supply

    OpenAIRE

    Farmer, Roger E.A.

    2007-01-01

    This paper is part of a broader project that provides a microfoundation to the General Theory of J.M. Keynes. I call this project 'old Keynesian economics' to distinguish it from new-Keynesian economics, a theory that is based on the idea that to make sense of Keynes we must assume that prices are sticky. I describe a multi-good model in which I interpret the definitions of aggregate demand and supply found in the General Theory through the lens of a search theory of the labor market. I argue...

  9. Aggregation of smooth preferences

    OpenAIRE

    Norman Schofield

    1998-01-01

    Suppose p is a smooth preference profile (for a society, N) belonging to a domain PN. Let be a voting rule, and (p)(x) be the set of alternatives in the space, W, which is preferred to x. The equilibrium E((p)) is the set {x∈W:(p)(x) is empty}. A sufficient condition for existence of E((p)) when p is convex is that a "dual", or generalized gradient, d(p)(x), is non-empty at all x. Under certain conditions the dual "field", d(p), admits a "social gradient field" (p). is called an "aggregator" ...

  10. Concrete = aggregate, cement, water?

    International Nuclear Information System (INIS)

    Concrete for the Temelin nuclear power plant is produced to about 70 different formulae. For quality production, homogeneous properties of aggregates, accurate proportioning devices, technological discipline and systematic inspections and tests should be assured. The results are reported of measuring compression strength after 28 days for different concrete samples. The results of such tests allow reducing the proportion of cement, which brings about considerable savings. Reduction in cement quantities can also be achieved by adding ash to the concrete mixes. Ligoplast, a plasticizer addition is used for improving workability. (M.D). 8 figs

  11. Multi-modality functional image guided dose escalation in the presence of uncertainties

    International Nuclear Information System (INIS)

    Background and purpose: In order to increase local tumour control by radiotherapy without increasing toxicity, it appears promising to harness functional imaging (FI) to guide dose to sub-volumes of the target with a high tumour load and perhaps de-escalate dose to low risk volumes, in order to maximise the efficiency of the deposited radiation dose. Methods and materials: A number of problems have to be solved to make focal dose escalation (FDE) efficient and safe: (1) how to combine ambiguous information from multiple imaging modalities; (2) how to take into account uncertainties of FI based tissue classification; (3) how to account for geometric uncertainties in treatment delivery; (4) how to add complementary FI modalities to an existing scheme. A generic optimisation concept addresses these points and is explicitly designed for clinical efficacy and for lowering the implementation threshold to FI-guided FDE. It combines classic tumour control probability modelling with a multi-variate logistic regression model of FI accuracy and an uncomplicated robust optimisation method. Results: Its key elements are (1) that dose is deposited optimally when it achieves equivalent expected effect everywhere in the target volume and (2) that one needs to cap the certainty about the absence of tumour anywhere in the target region. For illustration, an example of a PET/MR-guided FDE in prostate cancer is given. Conclusions: FDE can be safeguarded against FI uncertainties, at the price of a limit on the sensible dose escalation

  12. Mucosal healing in inflammatory bowel disease: Maintain or de-escalate therapy.

    Science.gov (United States)

    Cintolo, Marcello; Costantino, Giuseppe; Pallio, Socrate; Fries, Walter

    2016-02-15

    In the past decade, thanks to the introduction of biologic therapies, a new therapeutic goal, mucosal healing (MH), has been introduced. MH is the expression of an arrest of disease progression, resulting in minor hospitalizations, surgeries, and prolonged clinical remission. MH may be achieved with several therapeutic strategies reaching success rates up to 80% for both, ulcerative colitis (UC) and Crohn's disease (CD). Various scoring systems for UC and for the transmural CD, have been proposed to standardize the definition of MH. Several attempts have been undertaken to de-escalate therapy once MH is achieved, thus, reducing the risk of adverse events. In this review, we analysed the available studies regarding the achievement of MH and the subsequent treatment de-escalation according to disease type and administered therapy, together with non-invasive markers proposed as predictors for relapse. The available data are not encouraging since de-escalation after the achievement of MH is followed by a high number of clinical relapses reaching up to 50% within one year. Unclear is also another question, in case of combination therapies, which drug is more appropriate to stop, in order to guarantee a durable remission. Predictors of unfavourable outcome such as disease extension, perianal disease, or early onset disease appear to be inadequate to foresee behaviour of disease. Further studies are warranted to investigate the role of histologic healing for the further course of disease. PMID:26909224

  13. Macroevolutionary patterns of glucosinolate defense and tests of defense-escalation and resource availability hypotheses.

    Science.gov (United States)

    Cacho, N Ivalú; Kliebenstein, Daniel J; Strauss, Sharon Y

    2015-11-01

    We explored macroevolutionary patterns of plant chemical defense in Streptanthus (Brassicaceae), tested for evolutionary escalation of defense, as predicted by Ehrlich and Raven's plant-herbivore coevolutionary arms-race hypothesis, and tested whether species inhabiting low-resource or harsh environments invest more in defense, as predicted by the resource availability hypothesis (RAH). We conducted phylogenetically explicit analyses using glucosinolate profiles, soil nutrient analyses, and microhabitat bareness estimates across 30 species of Streptanthus inhabiting varied environments and soils. We found weak to moderate phylogenetic signal in glucosinolate classes and no signal in total glucosinolate production; a trend toward evolutionary de-escalation in the numbers and diversity of glucosinolates, accompanied by an evolutionary increase in the proportion of aliphatic glucosinolates; some support for the RAH relative to soil macronutrients, but not relative to serpentine soil use; and that the number of glucosinolates increases with microhabitat bareness, which is associated with increased herbivory and drought. Weak phylogenetic signal in chemical defense has been observed in other plant systems. A more holistic approach incorporating other forms of defense might be necessary to confidently reject escalation of defense. That defense increases with microhabitat bareness supports the hypothesis that habitat bareness is an underappreciated selective force on plants in harsh environments. PMID:26192213

  14. Terrorist attacks escalate in frequency and fatalities preceding highly lethal attacks.

    Directory of Open Access Journals (Sweden)

    Andy Martens

    Full Text Available Highly lethal terrorist attacks, which we define as those killing 21 or more people, account for 50% of the total number of people killed in all terrorist attacks combined, yet comprise only 3.5% of terrorist attacks. Given the disproportionate influence of these incidents, uncovering systematic patterns in attacks that precede and anticipate these highly lethal attacks may be of value for understanding attacks that exact a heavy toll on life. Here we examined whether the activity of terrorist groups escalates--both in the number of people killed per attack and in the frequency of attacks--leading up to highly lethal attacks. Analyses of terrorist attacks drawn from a state-of-the-art international terrorism database (The Global Terrorism Database showed evidence for both types of escalation leading up to highly lethal attacks, though complexities to the patterns emerged as well. These patterns of escalation do not emerge among terrorist groups that never commit a highly lethal attack.

  15. Crime scene analysis and the escalation of violence in serial rape.

    Science.gov (United States)

    Warren, J; Reboussin, R; Hazelwood, R R; Gibbs, N A; Trumbetta, S L; Cummings, A

    1999-03-15

    The current study examines the crime scene behavior manifest by 108 serial rapists responsible for the perpetration of 565 rapes across various cities within the US. The goal of the current study is to identify which aspects of crime scene behavior reported to law enforcement by the victim are most useful in predicting, early in a series of offenses, which rapists are most likely to escalate into higher and, at times, life threatening levels of violence. Using 58 scales that quantify the verbal, physical, and sexual behavior manifest by a rapist in his interaction with his victim during his first reported rape and 36 modal variables that summarized approach, timing, demographics, and weapon usage across the series of rapes, the study attempts to differentiate between those rapists who escalate in their use of blunt force (Increasers) from those who do not (Non-Increasers). A logistic regression indicates that rapists who are white rather than of minority status and who, at the time of their first reported rape, rape their victims for longer periods of time and use more profanity are more likely to escalate in their level of blunt force than those rapists who do not exhibit these behaviors. The relevance of this type of predictive framework for law enforcement in its attempts to prioritize particular investigations is discussed. PMID:10356773

  16. Escalating dose-multiple binge methamphetamine exposure results in degeneration of the neocortex and limbic system in the rat.

    Science.gov (United States)

    Kuczenski, Ronald; Everall, Ian P; Crews, Leslie; Adame, Anthony; Grant, Igor; Masliah, Eliezer

    2007-09-01

    Abuse of stimulant drugs such as methamphetamine (METH) and cocaine has been associated with long-lasting persistent behavioral alterations. Although METH-induced changes in the striatal dopaminergic system might play a role in these effects, the potential underlying neuroanatomical substrate for the chronic cognitive dysfunction in METH users is unclear. To investigate the involvement of non-dopaminergic systems in the neurotoxic effects of METH, we treated rats with an escalating dose-multiple binge regimen, which we have suggested may more closely simulate human METH exposure profiles. Combined neuropathological and stereological analyses showed that 30 days after the last binge, there was shrinkage and degeneration in the pyramidal cell layers of the frontal cortex and in the hippocampal CA3 region. Further immunocytochemical analysis showed that METH exposure resulted in loss of calbindin interneurons in the neocortex and selective damage to pyramidal neurons in the CA3 region of the hippocampus and granular cells in the dentate gyrus that was accompanied by microglial activation. Taken together, these studies suggest that selective degeneration of pyramidal neurons and interneurons in the neocortex and limbic system might be involved in the cognitive alterations in METH users. PMID:17603040

  17. Optimizing cancer radiotheraphy with 2-deoxy-D-glucose. Dose escalation studies in patients with glioblastoma multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Singh, D.; Gupta, J.P. [Dharmshila Cancer Hospital, New Delhi (India); Banerji, A.K. [Vidyasagar Inst. of Mental Health and Neurosciences, New Delhi (India); Dwarakanath, B.S.; Tripathi, R.P.; Mathew, T.L.; Ravindranath, T. [Institute of Nuclear Medicine and Allied Sciences, Delhi (India); Jain, V. [Wright State University, Dayton, OH (United States). Kettering Medical Center

    2005-08-01

    Background and purpose: Higher rates of glucose utilization and glycolysis generally correlate with poor prognosis in several types of malignant tumors. Own earlier studies on model systems demonstrated that the nonmetabolizable glucose analog 2-deoxy-D-glucose (2-DG) could enhance the efficacy of radiotherapy in a dose-dependent manner by selectively sensitizing cancer cells while protecting normal cells. Phase I/II clinical trials indicated that the combination of 2-DG, at an oral dose of 200 mg/kg body weight (BW), with large fractions of {gamma}-radiation was well tolerated in cerebral glioma patients. Since higher 2-DG doses are expected to improve the therapeutic gain, present studies were undertaken to examine the tolerance and safety of escalating 2-DG dose during combined treatment (2-DG + radiotherapy) in glioblastoma multiforme patients. Patients and methods: Untreated patients with histologically proven glioblastoma multiforme (WHO criteria) were included in the study. Seven weekly fractions of {sup 60}C {gamma}-rays (5 Gy/fraction) were delivered to the tumor volume (presurgical CT/MRI evaluation) plus 3 cm margin. Escalating 2-DG doses (200-250-300 mg/kg BW) were administered orally 30 min before irradiation after overnight fasting. Acute toxicity and tolerance were studied by monitoring the vital parameters and side effects. Late radiation damage and treatment responses were studied radiologically and clinically in surviving patients. Results: Transient side effects similar to hypoglycemia were observed in most of the patients. Tolerance and patient compliance to the combined treatment were very good up to a 2-DG dose of 250 mg/kg BW. However, at the higher dose of 300 mg/kg BW, two out of six patients were very restless and could not complete treatment, though significant changes in the vital parameters were not observed even at this dose. No significant damage to the normal brain tissue was observed during follow-up in seven out of ten patients who

  18. Dielectric approach to investigation of erythrocyte aggregation. II. Kinetics of erythrocyte aggregation-disaggregation in quiescent and flowing blood.

    Science.gov (United States)

    Pribush, A; Meiselman, H J; Meyerstein, D; Meyerstein, N

    2000-01-01

    A method based on dielectric properties of dispersed systems was applied to investigate the kinetics of RBC aggregation and the break-up of the aggregates. Experimentally, this method consists of measuring the capacitance at a frequency in the beginning of the beta-dispersion. Two experimental protocols were used to investigate the aggregation process. In the first case, blood samples were fully dispersed and then the flow was decreased or stopped to promote RBC aggregation. It was found that the initial phases of RBC aggregation are not affected by the shear rate. This finding indicates that RBC aggregation is a slow coagulation process. In the second case, RBCs aggregated under flow conditions at different shear rates and after the capacitance reached plateau levels, the flow was ceased. The steady-state capacitance of the quiescent blood and the kinetics of RBC aggregation after stoppage of shearing depend on the prior shear rate. To clarify the reasons for this effect, the kinetics of the disaggregation process was studied. In these experiments, time courses of the capacitance were recorded under different flow conditions and then a higher shear stress was applied to break up RBC aggregates. It was found that the kinetics of the disaggregation process depend on both the prior and current shear stresses. Results obtained in this study and their analysis show that the kinetics of RBC aggregation in stasis consists of two consecutive phases: At the onset, red blood cells interact face-to-face to form linear aggregates and then, after an accumulation of an appropriate concentration of these aggregates, branched rouleaux are formed via reactions of ends of the linear rouleaux with sides of other rouleaux (face-to-side interactions). Branching points are broken by low shear stresses whereas dispersion of the linear rouleaux requires significantly higher energy. PMID:11204548

  19. Fc block treatment, dead cells exclusion, and cell aggregates discrimination concur to prevent phenotypical artifacts in the analysis of subpopulations of tumor-infiltrating CD11b(+) myelomonocytic cells.

    Science.gov (United States)

    Kuonen, Francois; Touvrey, Cedric; Laurent, Julien; Ruegg, Curzio

    2010-11-01

    It is well established that cancer cells can recruit CD11b(+) myeloid cells to promote tumor angiogenesis and tumor growth. Increasing interest has emerged on the identification of subpopulations of tumor-infiltrating CD11b(+) myeloid cells using flow cytometry techniques. In the literature, however, discrepancies exist on the phenotype of these cells (Coffelt et al., Am J Pathol 2010;176:1564-1576). Since flow cytometry analysis requires particular precautions for accurate sample preparation and trustable data acquisition, analysis, and interpretation, some discrepancies might be due to technical reasons rather than biological grounds. We used the syngenic orthotopic 4T1 mammary tumor model in immunocompetent BALB/c mice to analyze and compare the phenotype of CD11b(+) myeloid cells isolated from peripheral blood and from tumors, using six-color flow cytometry. We report here that the nonspecific antibody binding through Fc receptors, the presence of dead cells and cell doublets in tumor-derived samples concur to generate artifacts in the phenotype of tumor-infiltrating CD11b(+) subpopulations. We show that the heterogeneity of tumor-infiltrating CD11b(+) subpopulations analyzed without particular precautions was greatly reduced upon Fc block treatment, dead cells, and cell doublets exclusion. Phenotyping of tumor-infiltrating CD11b(+) cells was particularly sensitive to these parameters compared to circulating CD11b(+) cells. Taken together, our results identify Fc block treatment, dead cells, and cell doublets exclusion as simple but crucial steps for the proper analysis of tumor-infiltrating CD11b(+) cell populations. PMID:20824631

  20. Lack of motor prediction, rather than perceptual conflict, evokes an odd sensation upon stepping onto a stopped escalator

    OpenAIRE

    Gomi, Hiroaki; Sakurada, Takeshi; Fukui, Takao

    2014-01-01

    When stepping onto a stopped escalator, we often perceive an “odd sensation” that is never felt when stepping onto stairs. The sight of an escalator provides a strong contextual cue that, in expectation of the backward acceleration when stepping on, triggers an anticipatory forward postural adjustment driven by a habitual and implicit motor process. Here we contrast two theories about why this postural change leads to an odd sensation. The first theory links the odd sensation to a lack of sen...

  1. Lack of motor prediction, rather than perceptual conflict, evokes an odd sensation upon stepping onto a stopped escalator

    OpenAIRE

    Hiroaki eGomi; Takeshi eSakurada; Takao eFukui

    2014-01-01

    When stepping onto a stopped escalator, we often perceive an odd sensation that is never felt when stepping onto stairs. The sight of an escalator provides a strong contextual cue that, in expectation of the backward acceleration when stepping on, triggers an anticipatory forward postural adjustment driven by a habitual and implicit motor process. . Here we contrast two theories about why this postural change leads to an odd sensation. The first theory links the odd sensation to a lack of se...

  2. Report on waste burial charges. Escalation of decommissioning waste disposal costs at low-level waste burial facilities, Revision 4

    International Nuclear Information System (INIS)

    One of the requirements placed upon nuclear power reactor licensees by the U.S. Nuclear Regulatory Commission (NRC) is for the licensees to periodically adjust the estimate of the cost of decommissioning their plants, in dollars of the current year, as part of the process to provide reasonable assurance that adequate funds for decommissioning will be available when needed. This report, which is scheduled to be revised periodically, contains the development of a formula for escalating decommissioning cost estimates that is acceptable to the NRC. The sources of information to be used in the escalation formula are identified, and the values developed for the escalation of radioactive waste burial costs, by site and by year, are given. The licensees may use the formula, the coefficients, and the burial escalation factors from this report in their escalation analyses, or they may use an escalation rate at least equal to the escalation approach presented herein. This fourth revision of NUREG-1307 contains revised spreadsheet results for the disposal costs for the reference PWR and the reference BWR and the ratios of disposal costs at the Washington, Nevada, and South Carolina sites for the years 1986, 1988, 1991 and 1993, superseding the values given in the May 1993 issue of this report. Burial cost surcharges mandated by the Low-Level Radioactive Waste Policy Amendments Act of 1985 (LLRWPAA) have been incorporated into the revised ratio tables for those years. In addition, spreadsheet results for the disposal costs for the reference reactors and ratios of disposal costs at the two remaining burial sites in Washington and South Carolina for the year 1994 are provided. These latter results do not include any LLRWPAA surcharges, since those provisions of the Act expired at the end of 1992. An example calculation for escalated disposal cost is presented, demonstrating the use of the data contained in this report

  3. Attenuating the escalation of commitment to a faltering project in decision-making groups : An implementation intention approach

    OpenAIRE

    Wieber, Frank; Thürmer, J. Lukas; Gollwitzer, Peter M.

    2015-01-01

    When groups receive negative feedback on their progress toward a set goal, they often escalate rather than temper their commitment. To attenuate such escalation, we suggest initiating a self-distancing response (i.e., taking the perspective of a neutral observer) by forming implementation intentions when, where, and how to act (i.e., making if-then plans). Implementation intentions should help groups to translate a self-distancing intention into action. In line with this reasoning, only group...

  4. Report on waste burial charges: Escalation of decommissioning waste disposal costs at Low-Level Waste Burial facilities. Revision 5

    International Nuclear Information System (INIS)

    One of the requirements placed upon nuclear power reactor licensees by the US Nuclear Regulatory Commission (NRC) is for the licensees to periodically adjust the estimate of the cost of decommissioning their plants, in dollars of the current year, as part of the process to provide reasonable assurance that adequate funds for decommissioning will be available when needed. This report, which is scheduled to be revised periodically, contains the development of a formula for escalating decommissioning cost estimates that is acceptable to the NRC. The sources of information to be used in the escalation formula are identified, and the values developed for the escalation of radioactive waste burial costs, by site and by year, are given. The licensees may use the formula, the coefficients, and the burial escalation factors from this report in their escalation analyses, or they may use an escalation rate at least equal to the escalation approach presented herein. This fifth revision of NUREG-1307 contains revised spreadsheet results for the disposal costs for the reference PWR and the reference BWR and the ratios of disposal costs at the Washington, Nevada, and South Carolina sites for the years 1986, 1988, 1991, 1993, and 1994, superseding the values given in the June 1994 issue of this report. Burial cost surcharges mandated by the Low-Level Radioactive Waste Policy Amendments Act of 1985 (LLRWPAA) have been incorporated into the revised ratio tables for those years. In addition, spreadsheet results for the disposal costs for the reference reactors and ratios of disposal costs at the two remaining burial sites in Washington and South Carolina for the year 1995 are provided. These latter results do not include any LLRWPAA surcharges, since those provisions of the Act expired at the end of 1992. An example calculation for escalated disposal cost is presented, demonstrating the use of the data contained in this report

  5. Tumor Necrosis Factor-Blocker Dose Escalation in Rheumatoid Arthritis Patients in a Pharmacy Benefit Management Setting

    OpenAIRE

    Blume, Steven W; Fox, Kathleen M.; Joseph, George; Chuang, Chien-Chia; Thomas, Jessy; Gandra, Shravanthi R

    2013-01-01

    Introduction Dose escalation with tumor necrosis factor (TNF)-blockers is poorly characterized in pharmacy benefit management (PBM) settings. Methods This retrospective study used integrated pharmacy and medical claims from the PBM Medco to characterize dose escalation among rheumatoid arthritis (RA) patients treated with etanercept and adalimumab. Data from adults with RA with pharmacy claims for etanercept or adalimumab between 1/1/2007 and 12/31/2009 and continuous enrollment for ≥6 months...

  6. Carrier Aggregation for LTE-Advanced

    DEFF Research Database (Denmark)

    Pedersen, Klaus Ingemann; Frederiksen, Frank; Rosa, Claudio;

    2011-01-01

    aggregated. This paper presents a summary of the supported CA scenarios as well as an overview of the CA functionality for LTE-Advanced with special emphasis on the basic concept, control mechanisms, and performance aspects. The discussion includes definitions of the new terms primary cell (PCell) and......Carrier aggregation (CA) is one of the key features for LTE-Advanced. By means of CA, users gain access to a total bandwidth of up to 100 MHz in order to meet the IMT-Advanced requirements. The system bandwidth may be contiguous, or composed of several non-contiguous bandwidth chunks, which are...... secondary cell (SCell), mechanisms for activation and deactivation of CCs, and the new cross-CC scheduling functionality for improved control channel optimizations. We also demonstrate how CA can be used as an enabler for simple yet effective frequency domain interference management schemes. In particular...

  7. Holographic characterization of protein aggregates

    Science.gov (United States)

    Wang, Chen; Zhong, Xiao; Ruffner, David; Stutt, Alexandra; Philips, Laura; Ward, Michael; Grier, David

    Holographic characterization directly measures the size distribution of subvisible protein aggregates in suspension and offers insights into their morphology. Based on holographic video microscopy, this analytical technique records and interprets holograms of individual aggregates in protein solutions as they flow down a microfluidic channel, without requiring labeling or other exceptional sample preparation. The hologram of an individual protein aggregate is analyzed in real time with the Lorenz-Mie theory of light scattering to measure that aggregate's size and optical properties. Detecting, counting and characterizing subvisible aggregates proceeds fast enough for time-resolved studies, and lends itself to tracking trends in protein aggregation arising from changing environmental factors. No other analytical technique provides such a wealth of particle-resolved characterization data in situ. Holographic characterization promises accelerated development of therapeutic protein formulations, improved process control during manufacturing, and streamlined quality assurance during storage and at the point of use. Mrsec and MRI program of the NSF, Spheryx Inc.

  8. Frequency, Size, and Localization of Bacterial Aggregates on Bean Leaf Surfaces

    Science.gov (United States)

    Monier, J.-M.; Lindow, S. E.

    2004-01-01

    Using epifluorescence microscopy and image analysis, we have quantitatively described the frequency, size, and spatial distribution of bacterial aggregates on leaf surfaces of greenhouse-grown bean plants inoculated with the plant-pathogenic bacterium Pseudomonas syringae pv. syringae strain B728a. Bacterial cells were not randomly distributed on the leaf surface but occurred in a wide range of cluster sizes, ranging from single cells to over 104 cells per aggregate. The average cluster size increased through time, and aggregates were more numerous and larger when plants were maintained under conditions of high relative humidity levels than under dry conditions. The large majority of aggregates observed were small (less than 100 cells), and aggregate sizes exhibited a strong right-hand-skewed frequency distribution. While large aggregates are not frequent on a given leaf, they often accounted for the majority of cells present. We observed that up to 50% of cells present on a leaf were located in aggregates containing 103 cells or more. Aggregates were associated with several different anatomical features of the leaf surface but not with stomates. Aggregates were preferentially associated with glandular trichomes and veins. The biological and ecological significance of aggregate formation by epiphytic bacteria is discussed. PMID:14711662

  9. Aggregation in Large Dynamic Panels

    OpenAIRE

    Pesaran, Mohammad Hashem; Chudik, Alexander

    2011-01-01

    This paper considers the problem of aggregation in the case of large linear dynamic panels, where each micro unit is potentially related to all other micro units, and where micro innovations are allowed to be cross sectionally dependent. Following Pesaran (2003), an optimal aggregate function is derived, and the limiting behavior of the aggregation error is investigated as N (the number of cross section units) increases. Certain distributional features of micro parameters are also identi...

  10. Modifiers of mutant huntingtin aggregation

    OpenAIRE

    Teuling, Eva; Bourgonje, Annika; Veenje, Sven; Thijssen, Karen; Boer, Jelle de; van der Velde, Joeri; Swertz, Morris; Nollen, Ellen

    2011-01-01

    Protein aggregation is a common hallmark of a number of age-related neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and polyglutamine-expansion disorders such as Huntington’s disease, but how aggregation-prone proteins lead to pathology is not known. Using a genome-wide RNAi screen in a C. elegans-model for polyglutamine aggregation, we previously identified 186 genes that suppress aggregation. Using an RNAi screen for human orthologs of these genes, we here present 26 human g...

  11. Aggregation dynamics of rigid polyelectrolytes

    Science.gov (United States)

    Tom, Anvy Moly; Rajesh, R.; Vemparala, Satyavani

    2016-01-01

    Similarly charged polyelectrolytes are known to attract each other and aggregate into bundles when the charge density of the polymers exceeds a critical value that depends on the valency of the counterions. The dynamics of aggregation of such rigid polyelectrolytes are studied using large scale molecular dynamics simulations. We find that the morphology of the aggregates depends on the value of the charge density of the polymers. For values close to the critical value, the shape of the aggregates is cylindrical with height equal to the length of a single polyelectrolyte chain. However, for larger values of charge, the linear extent of the aggregates increases as more and more polymers aggregate. In both the cases, we show that the number of aggregates decrease with time as power laws with exponents that are not numerically distinguishable from each other and are independent of charge density of the polymers, valency of the counterions, density, and length of the polyelectrolyte chain. We model the aggregation dynamics using the Smoluchowski coagulation equation with kernels determined from the molecular dynamics simulations and justify the numerically obtained value of the exponent. Our results suggest that once counterions condense, effective interactions between polyelectrolyte chains short-ranged and the aggregation of polyelectrolytes are diffusion-limited.

  12. Novel aspects of platelet aggregation

    Directory of Open Access Journals (Sweden)

    Roka-Moya Y. M.

    2014-01-01

    Full Text Available The platelet aggregation is an important process, which is critical for the hemostatic plug formation and thrombosis. Recent studies have shown that the platelet aggregation is more complex and dynamic than it was previously thought. There are several mechanisms that can initiate the platelet aggregation and each of them operates under specific conditions in vivo. At the same time, the influence of certain plasma proteins on this process should be considered. This review intends to summarize the recent data concerning the adhesive molecules and their receptors, which provide the platelet aggregation under different conditions.

  13. Fractal Aggregation Under Rotation

    Institute of Scientific and Technical Information of China (English)

    WUFeng-Min; WULi-Li; LUHang-Jun; LIQiao-Wen; YEGao-Xiang

    2004-01-01

    By means of the Monte Carlo simulation, a fractal growth model is introduced to describe diffusion-limited aggregation (DLA) under rotation. Patterns which are different from the classical DLA model are observed and the fractal dimension of such clusters is calculated. It is found that the pattern of the clusters and their fractal dimension depend strongly on the rotation velocity of the diffusing particle. Our results indicate the transition from fractal to non-fractal behavior of growing cluster with increasing rotation velocity, i.e. for small enough angular velocity ω; thefractal dimension decreases with increasing ω;, but then, with increasing rotation velocity, the fractal dimension increases and the cluster becomes compact and tends to non-fractal.

  14. Fractal Aggregation Under Rotation

    Institute of Scientific and Technical Information of China (English)

    WU Feng-Min; WU Li-Li; LU Hang-Jun; LI Qiao-Wen; YE Gao-Xiang

    2004-01-01

    By means of the Monte Carlo simulation, a fractal growth model is introduced to describe diffusion-limited aggregation (DLA) under rotation. Patterns which are different from the classical DLA model are observed and the fractal dimension of such clusters is calculated. It is found that the pattern of the clusters and their fractal dimension depend strongly on the rotation velocity of the diffusing particle. Our results indicate the transition from fractal to non-fractal behavior of growing cluster with increasing rotation velocity, i.e. for small enough angular velocity ω the fractal dimension decreases with increasing ω, but then, with increasing rotation velocity, the fractal dimension increases and the cluster becomes compact and tends to non-fractal.

  15. Inhibition of UCH-L1 in oligodendroglial cells results in microtubule stabilization and prevents α-synuclein aggregate formation by activating the autophagic pathway: implications for multiple system atrophy

    Directory of Open Access Journals (Sweden)

    Katharina Pukaß

    2015-05-01

    Full Text Available α-Synuclein (α-syn positive glial cytoplasmic inclusions (GCI originating in oligodendrocytes are a characteristic hallmark in multiple system atrophy. Their occurrence may be linked to a failure of the ubiquitin proteasome system (UPS or the autophagic pathway. For proteasomal degradation, proteins need to be covalently modified by ubiquitin, and deubiquitinated by deubiquitinating enzymes before proteolytic degradation is performed. The deubiquitinating enzyme UCH-L1 is a component of the UPS, it is abundantly expressed in neuronal brain cells and has been connected to Parkinson`s disease. It interacts with α-syn and tubulin. The present study was undertaken to investigate whether UCH-L1 is a constituent of oligodendrocytes, the myelin forming cells of the CNS, and is associated with GCIs in MSA. Furthermore, LDN-57444 (LDN, a specific UCH-L1 inhibitor, was used to analyze its effects on cell morphology, microtubule organization and the proteolytic degradation system. Towards this an oligodendroglial cell line (OLN cells, stably transfected with α-syn or with α-syn and GFP-LC3, to monitor the autophagic flux, was used. The data show that UCHL-1 is expressed in oligodendrocytes derived from the brains of newborn rats and colocalizes with α-syn in GCIs of MSA brain sections. LDN treatment had a direct impact on the microtubule network by affecting tubulin posttranslational modifications, i.e. acetylation and tyrosination. An increase in α-tubulin detyrosination was observed and detyrosinated microtubules were abundantly recruited to the cellular extensions. Furthermore, small α-syn aggregates, which are constitutively expressed in OLN cells overexpressing α-syn, were abolished, and LDN caused the upregulation of the autophagic pathway. Our data add to the knowledge that the UPS and the autophagy-lysosomal pathway are tightly balanced, and that UCH-L1 and its regulation may play a role in neurodegenerative diseases with oligodendroglia

  16. Research on Judgment Aggregation Based on Logic

    OpenAIRE

    Li Dai; Jihua Zhang

    2014-01-01

    Preference aggregation and judgment aggregation are two basic research models of group decision making. And preference aggregation has been deeply studied in social choice theory. However, researches of social choice theory gradually focus on judgment aggregation which appears recently. Judgment aggregation focuses on how to aggregate many consistent logical formulas into one, from the perspective of logic. We try to start with judgment aggregation model based on logic and then explore differ...

  17. Dose Escalation and Healthcare Resource Use among Ulcerative Colitis Patients Treated with Adalimumab in English Hospitals: An Analysis of Real-World Data.

    Directory of Open Access Journals (Sweden)

    Christopher M Black

    Full Text Available To describe the real-world use of adalimumab for maintenance treatment of ulcerative colitis (UC and associated healthcare costs in English hospitals.Retrospective cohort study.Analysis of NHS Hospital Episode Statistics linked with pharmacy dispensing data in English hospitals.Adult UC patients receiving ≥240mg during adalimumab treatment induction, subsequently maintained on adalimumab.Frequency and pattern of adalimumab use and dose escalation during maintenance treatment and associated healthcare costs (prescriptions and hospital visits.191 UC patients completed adalimumab treatment induction. 83 (43.46% dose escalated during maintenance treatment by ≥100% (equivalent to weekly dosing (median time to dose escalation: 139 days. 56 patients (67.47% subsequently de-escalated by ≥50% (median time to dose de-escalation: 21 days. Mean all-cause healthcare costs for all patients ≤12 months of index were £13,892. Dose escalators incurred greater mean healthcare costs than non-escalators ≤12 months of index (£14,596 vs. £13,351. Prescriptions accounted for 96.49% of UC-related healthcare costs (£11,090 of £11,494 in all patients.Within the cohort, 43.46% of UC patients escalated their adalimumab dose by ≥100% and incurred greater costs than non-escalators. The apparent underestimation of adalimumab dose escalation in previous studies may have resulted in underestimated costs in healthcare systems.

  18. Topics in Probabilistic Judgment Aggregation

    Science.gov (United States)

    Wang, Guanchun

    2011-01-01

    This dissertation is a compilation of several studies that are united by their relevance to probabilistic judgment aggregation. In the face of complex and uncertain events, panels of judges are frequently consulted to provide probabilistic forecasts, and aggregation of such estimates in groups often yield better results than could have been made…

  19. J-aggregates, v.2

    CERN Document Server

    Kobayashi, Takayoshi

    2012-01-01

    This work deals with J-aggregates, which have a long history of research. The volume covers electronic states, linear and nonlinear optical properties. Various properties and processes of J-aggregates, such as super-radiance, excitons, photon echo, geometrical structure, electron transfer and femtosecond spectroscopy, are discussed.

  20. Suppression of Platelet Aggregation by Bordetella pertussis Adenylate Cyclase Toxin

    OpenAIRE

    Iwaki, Masaaki; Kamachi, Kazunari; Heveker, Nikolaus; Konda, Toshifumi

    1999-01-01

    The effect of Bordetella pertussis adenylate cyclase toxin (ACT) on platelet aggregation was investigated. This cell-invasive adenylate cyclase completely suppressed ADP (10 μM)-induced aggregation of rabbit platelets at 3 μg/ml and strongly suppressed thrombin (0.2 U/ml)-induced aggregation at 10 μg/ml. The suppression was accompanied by marked increase in platelet intracellular cyclic AMP (cAMP) content and was diminished by the anti-ACT monoclonal antibody B7E11. A catalytically inactive p...

  1. Skills escalator in allied health: a time for reflection and refocus

    Directory of Open Access Journals (Sweden)

    Gilmore LG

    2011-09-01

    Full Text Available Lisa G Gilmore1, Joanne H Morris1, Karen Murphy2, Karen Grimmer-Somers3, Saravana Kumar31The Canberra Hospital, ACT Government Health Directorate, Canberra, ACT; 2ACT Government Health Directorate, Canberra, ACT; 3International Centre for Allied Evidence, University of South Australia, Adelaide, SA, AustraliaAbstract: It is abundantly clear that the health workforce of tomorrow will meet a number of unique challenges. There are a number of drivers for this, including the changing demographics of patients and health professionals, changing working patterns and mobility of the health workforce, evolving models of care, emerging evidence base, altering funding models, and the need to underpin health care service delivery with safety, effectiveness, patient centeredness, efficiency, equity, and timeliness. It is in this time of change that role extension within health disciplines is seen as an important tool to meet some of these challenges. Role extension is viewed as a skills escalator, where practitioners move up the skills escalator within the scope of their discipline, to advance it and then, with training, extend it. Within allied health, in some disciplines, advanced and extended scope of practice initiatives have mushroomed. Often these initiatives have been ad hoc, and opportunistically created in response to local needs and requirements. As these initiatives are local and context-dependent, to date there is very little uniformity or congruency between these initiatives. This has led to variability in implementation, lack of rigorous evaluations and, ultimately, poor long-term sustainability. In this paper, we reflect on a number of key issues, drawing on our own experiences in undertaking such initiatives, which need to be taken into account when considering advanced and extended scope of practice for allied health.Keywords: allied health, skill escalation, extended scope of practice, advanced scope of practice

  2. Dose escalation of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma

    International Nuclear Information System (INIS)

    Objective: To define the maximum-tolerated dose (MTD) and observe the side effect of escalating cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma in Chinese, with toxicity studied. Methods: Previously untreated fifteen Chinese patients suffering from esophageal carcinoma received conventional fractionation radiotherapy, with 5 daily fractions of 2.0 Gy per week. The total radiation dose was 60 Gy. Concurrent chemotherapy dose escalation was given by the relatively safe and kidney-sparing modified Fibonacci sequence. The starting dose was cisplatin 37.5 mg/m2 D1 and 5-fluorouracil 500 mg/m2 D1-5, respectively. This regimen was repeated 4 times every 28 days. Escalation dose was cisplatin 7.5 mg/m2 and 5- fluorouracil 100 mg/m2. Every. cohort contained at least 3 patients. If no dose-limiting toxicity(DLT) was observed, the next dose level was opened for entry. These courses were repeated until DLT appeared. MTD was declared as one dose level below which DLT appeared. Results: DLT was defined as grade 3 radiation-induced esophagitis at the level of cisplatin 60 mg/m2, 5-fluorouracil 700 mg/m2. MTD was defined as cisplatin 52.5 mg/m2, 5- fiuorouracil 700 mg/m2. The major side effect were radiation-induced esophagitis, leucopenia, nausea, vomiting and anorexia. Conclusion: Maximun tolerated dose of cisplatin with 5-fiuorouracil in concurrent ehemoradiotherapy in the Chinese people with esophageal carcinoma were eisplatin 52.5 mg/m2 D1,5-fluorouracil 700 mg/m2 D1-5, repeated 4 times every 28 days. (authors)

  3. Validation of treatment escalation as a definition of atopic eczema flares.

    Directory of Open Access Journals (Sweden)

    Kim S Thomas

    Full Text Available Atopic eczema (AE is a chronic disease with flares and remissions. Long-term control of AE flares has been identified as a core outcome domain for AE trials. However, it is unclear how flares should be defined and measured.To validate two concepts of AE flares based on daily reports of topical medication use: (i escalation of treatment and (ii days of topical anti-inflammatory medication use (topical corticosteroids and/or calcineurin inhibitors.Data from two published AE studies (studies A (n=336 and B (n=60 were analysed separately. Validity and feasibility of flare definitions were assessed using daily global bother (scale 0 to 10 as the reference standard. Intra-class correlations were reported for continuous variables, and odds ratios and area under the receiver operator characteristic (ROC curve for binary outcome measures.Good agreement was found between both AE flare definitions and change in global bother: area under the ROC curve for treatment escalation of 0.70 and 0.73 in studies A and B respectively, and area under the ROC curve of 0.69 for topical anti-inflammatory medication use (Study A only. Significant positive relationships were found between validated severity scales (POEM, SASSAD, TIS and the duration of AE flares occurring in the previous week - POEM and SASSAD rose by half a point for each unit increase in number of days in flare. Smaller increases were observed on the TIS scale. Completeness of daily diaries was 95% for Study A and 60% for Study B over 16 weeks.Both definitions were good proxy indicators of AE flares. We found no evidence that 'escalation of treatment' was a better measure of AE flares than 'use of topical anti-inflammatory medications'. Capturing disease flares in AE trials through daily recording of medication use is feasible and appears to be a good indicator of long-term control.Current Controlled Trials ISRCTN71423189 (Study A.

  4. Biological modelling of the radiation dose escalation effect of regional hyperthermia in cervical cancer

    International Nuclear Information System (INIS)

    Locoregional hyperthermia combined with radiotherapy significantly improves locoregional control and overall survival for cervical tumors compared to radiotherapy alone. In this study biological modelling is applied to quantify the effect of radiosensitization for three cervical cancer patients to evaluate the improvement in equivalent dose for the combination treatment with radiotherapy and hyperthermia. The Linear-Quadratic (LQ) model extended with temperature-dependent LQ-parameters α and β was used to model radiosensitization by hyperthermia and to calculate the conventional radiation dose that is equivalent in biological effect to the combined radiotherapy and hyperthermia treatment. External beam radiotherapy planning was performed based on a prescription dose of 46Gy in 23 fractions of 2Gy. Hyperthermia treatment using the AMC-4 system was simulated based on the actual optimized system settings used during treatment. The simulated hyperthermia treatments for the 3 patients yielded a T50 of 40.1 °C, 40.5 °C, 41.1 °C and a T90 of 39.2 °C, 39.7 °C, 40.4 °C, respectively. The combined radiotherapy and hyperthermia treatment resulted in a D95 of 52.5Gy, 55.5Gy, 56.9Gy in the GTV, a dose escalation of 7.3–11.9Gy compared to radiotherapy alone (D95 = 45.0–45.5Gy). This study applied biological modelling to evaluate radiosensitization by hyperthermia as a radiation-dose escalation for cervical cancer patients. This model is very useful to compare the effectiveness of different treatment schedules for combined radiotherapy and hyperthermia treatments and to guide the design of clinical studies on dose escalation using hyperthermia in a multi-modality setting

  5. Molecular aggregation of humic substances

    Science.gov (United States)

    Wershaw, R. L.

    1999-01-01

    Humic substances (HS) form molecular aggregates in solution and on mineral surfaces. Elucidation of the mechanism of formation of these aggregates is important for an understanding of the interactions of HS in soils arid natural waters. The HS are formed mainly by enzymatic depolymerization and oxidation of plant biopolymers. These reactions transform the aromatic and lipid plant components into amphiphilic molecules, that is, molecules that consist of separate hydrophobic (nonpolar) and hydrophilic (polar) parts. The nonpolar parts of the molecules are composed of relatively unaltered segments of plant polymers and the polar parts of carboxylic acid groups. These amphiphiles form membrane-like aggregates on mineral surfaces and micelle-like aggregates in solution. The exterior surfaces of these aggregates are hydrophilic, and the interiors constitute separate hydrophobic liquid-like phases.

  6. Immunogenicity of Therapeutic Protein Aggregates.

    Science.gov (United States)

    Moussa, Ehab M; Panchal, Jainik P; Moorthy, Balakrishnan S; Blum, Janice S; Joubert, Marisa K; Narhi, Linda O; Topp, Elizabeth M

    2016-02-01

    Therapeutic proteins have a propensity for aggregation during manufacturing, shipping, and storage. The presence of aggregates in protein drug products can induce adverse immune responses in patients that may affect safety and efficacy, and so it is of concern to both manufacturers and regulatory agencies. In this vein, there is a lack of understanding of the physicochemical determinants of immunological responses and a lack of standardized analytical methods to survey the molecular properties of aggregates associated with immune activation. In this review, we provide an overview of the basic immune mechanisms in the context of interactions with protein aggregates. We then critically examine the literature with emphasis on the underlying immune mechanisms as they relate to aggregate properties. Finally, we highlight the gaps in our current understanding of this issue and offer recommendations for future research. PMID:26869409

  7. DRAG ON SUBMICRON NANOPARTICLE AGGREGATES

    Institute of Scientific and Technical Information of China (English)

    F.; Einar; Kruis

    2005-01-01

    A new procedure was developed for estimating the effective collision diameter of an aggregate composed of primary particles of any size. The coagulation coefficient of two oppositely charged particles was measured experimentally and compared with classic Fuchs theory, including a new method to account for particle non-sphericity. A second set of experiments were performed on well-defined nanoparticle aggregates at different stages of sintering, i.e. from the aggregate to the fully sintered stage. Here, electrical mobility was used to characterize the particle drag. The aggregates are being built from two different size-fractionated nanoparticle aerosols, the non-aggregated particles are discarded by an electrofilter and then they are passed through a furnace at concentrations low enough not to induce coagulation.

  8. Mechanics of fire ant aggregations

    Science.gov (United States)

    Tennenbaum, Michael; Liu, Zhongyang; Hu, David; Fernandez-Nieves, Alberto

    2016-01-01

    Fire ants link their bodies to form aggregations; these can adopt a variety of structures, they can drip and spread, or withstand applied loads. Here, by using oscillatory rheology, we show that fire ant aggregations are viscoelastic. We find that, at the lowest ant densities probed and in the linear regime, the elastic and viscous moduli are essentially identical over the spanned frequency range, which highlights the absence of a dominant mode of structural relaxation. As ant density increases, the elastic modulus rises, which we interpret by alluding to ant crowding and subsequent jamming. When deformed beyond the linear regime, the aggregation flows, exhibiting shear-thinning behaviour with a stress load that is comparable to the maximum load the aggregation can withstand before individual ants are torn apart. Our findings illustrate the rich, collective mechanical behaviour that can arise in aggregations of active, interacting building blocks.

  9. Feasibility of extreme dose escalation for glioblastoma multiforme using 4π radiotherapy

    International Nuclear Information System (INIS)

    Glioblastoma multiforme (GBM) frequently recurs at the same location after radiotherapy. Further dose escalation using conventional methods is limited by normal tissue tolerance. 4π non-coplanar radiotherapy has recently emerged as a new potential method to deliver highly conformal radiation dose using the C-arm linacs. We aim to study the feasibility of very substantial GBM dose escalation while maintaining normal tissue tolerance using 4π. 11 GBM patients previously treated with volumetric modulated arc therapy (VMAT/RapidArc) on the NovalisTx™ platform to a prescription dose of either 59.4 Gy or 60 Gy were included. All patients were replanned with 30 non-coplanar beams using a 4π radiotherapy platform, which inverse optimizes both beam angles and fluence maps. Four different prescriptions were used including original prescription dose and PTV (4πPTVPD), 100 Gy to the PTV and GTV (4πPTV100Gy), 100 Gy to the GTV only while maintaining prescription dose to the rest of the PTV (4πGTV100Gy), and a 5 mm margin expansion plan (4πPTVPD+5mm). OARs included in the study are the normal brain (brain – PTV), brainstem, chiasm, spinal cord, eyes, lenses, optical nerves, and cochleae. The 4π plans resulted in superior dose gradient indices, as indicated by >20% reduction in the R50, compared to the clinical plans. Among all of the 4π cases, when compared to the clinical plans, the maximum and mean doses were significantly reduced (p < 0.05) by a range of 47.01-98.82% and 51.87-99.47%, respectively, or unchanged (p > 0.05) for all of the non-brain OARs. Both the 4πPTVPD and 4π GTV100GYplans reduced the mean normal brain mean doses. 4π non-coplanar radiotherapy substantially increases the dose gradient outside of the PTV and better spares critical organs. Dose escalation to 100 Gy to the GTV or additional margin expansion while meeting clinical critical organ dose constraints is feasible. 100 Gy to the PTV result in higher normal brain doses but may be tolerated

  10. Tomotherapy PET-guided dose escalation. A dosimetric feasibility study for patients with malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    The aim of this study was to investigate whether a safe escalation of the dose to the pleural cavity and PET/CT-positive areas in patients with unresectable malignant pleural mesothelioma (MPM) is possible using helical tomotherapy (HT). We selected 12 patients with MPM. Three planning strategies were investigated. In the first strategy (standard treatment), treated comprised a prescribed median dose to the planning target volume (PTV) boost (PTV1) of 64.5 Gy (range: 56 Gy/28 fractions to 66 Gy/30 fractions) and 51 Gy (range: 50.4 Gy/28 fractions to 54 Gy/30 fractions) to the pleura PTV (PTV2). Thereafter, for each patient, two dose escalation plans were generated prescribing 62.5 and 70 Gy (2.5 and 2.8 Gy/fraction, respectively) to the PTV1 and 56 Gy (2.24 Gy/fraction) to the PTV2, in 25 fractions. Dose-volume histogram (DVH) constraints and normal tissue complication probability (NTCP) calculations were used to evaluate the differences between the plans. For all plans, the 95 % PTVs received at least 95 % of the prescribed dose. For all patients, it was possible to perform the dose escalation in accordance with the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) constraints for organs at risk (OARs). The average contralateral lung dose was < 8 Gy. NTCP values for OARs did not increase significantly compared with the standard treatment (p > 0.05), except for the ipsilateral lung. For all plans, the lung volume ratio was strongly correlated with the V20, V30, and V40 DVHs of the lung (p < 0.0003) and with the lung mean dose (p < 0.0001). The results of this study suggest that by using HT it is possible to safely escalate the dose delivery to at least 62.5 Gy in PET-positive areas while treating the pleural cavity to 56 Gy in 25 fractions without significantly increasing the dose to the surrounding normal organs. (orig.)

  11. Dose escalated radiotherapy for T1 and T2 nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Nasopharyngeal carcinoma (NPC) is most prevalent in the Guangzhou province in southern China, in Hong Kong and in Singapore. It also occurs in Europe and North America, partly due to its epidemiological association with the woodworking and shoe manufacturing industry. Because of its anatomical location, i.e. so close to vital organs at risk, such as the brain stem and eyes, the technique of radiotherapy and dose/fractionation prescription is of extreme importance. This communication describes our experience with dose escalation radiotherapy for stages T1 and T2 of NPC. (author)

  12. Regional-employment impact of rapidly escalating energy costs. [Riverside-San Bernardino SMSA

    Energy Technology Data Exchange (ETDEWEB)

    Kolk, D.X.

    1983-04-01

    This paper presents a methodology for incorporating price-induced technological substitution into a regional input-output forecasting model. The model was used to determine the employment impacts of rapidly escalating energy costs on the Riverside-San Bernardino (California) SMSA. The results indicate that the substitution effect between energy and other goods was dominated by the income effect. A reallocation of consumer expenditures from labor-intensive to energy-intensive goods occurred, resulting in a two- to threefold increase in the unemployment rate among low-skilled individuals. 18 references, 5 tables.

  13. Who rides the glass escalator? Gender, race and nationality in the national nursing assistant study

    OpenAIRE

    Kim Price-Glynn; Carter Rakovski

    2012-01-01

    Evidence for Christine Williams’s ‘glass escalator’ effect documents how professional men entering female-dominated occupations may advance more quickly toward authority positions and higher salaries. However, studies of men’s benefits from occupational segregation have neglected low-wage and diverse groups of workers. Using the representative US National Nursing Assistant Study (NNAS), the article examines organizational measures of inequality and discrimination – wages, benefits a...

  14. RankAggreg, an R package for weighted rank aggregation

    Directory of Open Access Journals (Sweden)

    Datta Susmita

    2009-02-01

    Full Text Available Abstract Background Researchers in the field of bioinformatics often face a challenge of combining several ordered lists in a proper and efficient manner. Rank aggregation techniques offer a general and flexible framework that allows one to objectively perform the necessary aggregation. With the rapid growth of high-throughput genomic and proteomic studies, the potential utility of rank aggregation in the context of meta-analysis becomes even more apparent. One of the major strengths of rank-based aggregation is the ability to combine lists coming from different sources and platforms, for example different microarray chips, which may or may not be directly comparable otherwise. Results The RankAggreg package provides two methods for combining the ordered lists: the Cross-Entropy method and the Genetic Algorithm. Two examples of rank aggregation using the package are given in the manuscript: one in the context of clustering based on gene expression, and the other one in the context of meta-analysis of prostate cancer microarray experiments. Conclusion The two examples described in the manuscript clearly show the utility of the RankAggreg package in the current bioinformatics context where ordered lists are routinely produced as a result of modern high-throughput technologies.

  15. Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation

    Science.gov (United States)

    López, Laura C.; Varea, Olga; Navarro, Susanna; Carrodeguas, José A.; Sanchez de Groot, Natalia; Ventura, Salvador; Sancho, Javier

    2016-01-01

    Human Amylin, or islet amyloid polypeptide (hIAPP), is a small hormone secreted by pancreatic β-cells that forms aggregates under insulin deficiency metabolic conditions, and it constitutes a pathological hallmark of type II diabetes mellitus. In type II diabetes patients, amylin is abnormally increased, self-assembled into amyloid aggregates, and ultimately contributes to the apoptotic death of β-cells by mechanisms that are not completely understood. We have screened a library of approved drugs in order to identify inhibitors of amylin aggregation that could be used as tools to investigate the role of amylin aggregation in type II diabetes or as therapeutics in order to reduce β-cell damage. Interestingly, three of the compounds analyzed—benzbromarone, quercetin, and folic acid—are able to slow down amylin fiber formation according to Thioflavin T binding, turbidimetry, and Transmission Electron Microscopy assays. In addition to the in vitro assays, we have tested the effect of these compounds in an amyloid toxicity cell culture model and we have found that one of them, quercetin, has the ability to partly protect cultured pancreatic insulinoma cells from the cytotoxic effect of amylin. Our data suggests that quercetin can contribute to reduce oxidative damage in pancreatic insulinoma β cells by modulating the aggregation propensity of amylin. PMID:27322259

  16. Liver tissue engineering based on aggregate assembly: efficient formation of endothelialized rat hepatocyte aggregates and their immobilization with biodegradable fibres

    International Nuclear Information System (INIS)

    To realize long-term in vitro culture of hepatocytes at a high density while maintaining a high hepatic function for aggregate-based liver tissue engineering, we report here a novel culture method whereby endothelialized rat hepatocyte aggregates were formed using a PDMS microwell device and cultured in a perfusion bioreactor by introducing spacers between aggregates to improve oxygen and nutrient supply. Primary rat hepatocyte aggregates around 100 µm in diameter coated with human umbilical vein endothelial cells were spontaneously and quickly formed after 12 h of incubation, thanks to the continuous supply of oxygen by diffusion through the PDMS honeycomb microwell device. Then, the recovered endothelialized rat hepatocyte aggregates were mixed with biodegradable poly-l-lactic acid fibres in suspension and packed into a PDMS-based bioreactor. Perfusion culture of 7 days was successfully achieved with more than 73.8% cells retained in the bioreactor. As expected, the fibres acted as spacers between aggregates, which was evidenced from the enhanced albumin production and more spherical morphology compared with fibre-free packing. In summary, this study shows the advantages of using PDMS-based microwells to form heterotypic aggregates and also demonstrates the feasibility of spacing tissue elements for improving oxygen and nutrient supply to tissue engineering based on modular assembly. (paper)

  17. Perspectives on Preference Aggregation.

    Science.gov (United States)

    Regenwetter, Michel

    2009-07-01

    For centuries, the mathematical aggregation of preferences by groups, organizations, or society itself has received keen interdisciplinary attention. Extensive theoretical work in economics and political science throughout the second half of the 20th century has highlighted the idea that competing notions of rational social choice intrinsically contradict each other. This has led some researchers to consider coherent democratic decision making to be a mathematical impossibility. Recent empirical work in psychology qualifies that view. This nontechnical review sketches a quantitative research paradigm for the behavioral investigation of mathematical social choice rules on real ballots, experimental choices, or attitudinal survey data. The article poses a series of open questions. Some classical work sometimes makes assumptions about voter preferences that are descriptively invalid. Do such technical assumptions lead the theory astray? How can empirical work inform the formulation of meaningful theoretical primitives? Classical "impossibility results" leverage the fact that certain desirable mathematical properties logically cannot hold in all conceivable electorates. Do these properties nonetheless hold true in empirical distributions of preferences? Will future behavioral analyses continue to contradict the expectations of established theory? Under what conditions do competing consensus methods yield identical outcomes and why do they do so? PMID:26158988

  18. SU-E-T-622: Identification and Improvement of Patients Eligible for Dose Escalation with Matched Plans

    Energy Technology Data Exchange (ETDEWEB)

    Bush, K; Holcombe, C; Kapp, D; Buyyounouski, M; Hancock, S; Xing, L; Atwood, T; King, M [Department of Radiation Oncology, Stanford School of Medicine, Stanford, CA (United States)

    2014-06-15

    Purpose: Radiation-therapy dose-escalation beyond 80Gy may improve tumor control rates for patients with localized prostate cancer. Since toxicity remains a concern, treatment planners must achieve dose-escalation while still adhering to dose-constraints for surrounding structures. Patientmatching is a machine-learning technique that identifies prior patients that dosimetrically match DVH parameters of target volumes and critical structures prior to actual treatment planning. We evaluated the feasibility of patient-matching in (1)identifying candidates for safe dose-escalation; and (2)improving DVH parameters for critical structures in actual dose-escalated plans. Methods: We analyzed DVH parameters from 319 historical treatment plans to determine which plans could achieve dose-escalation (8640cGy) without exceeding Zelefsky dose-constraints (rectal and bladder V47Gy<53%, and V75.6Gy<30%, max-point dose to rectum of 8550cGy, max dose to PTV< 9504cGy). We then estimated the percentage of cases that could achieve safe dose-escalation using software that enables patient matching (QuickMatch, Siris Medical, Mountain View, CA). We then replanned a case that had violated DVH constraints with DVH parameters from patient matching, in order to determine whether this previously unacceptable plan could be made eligible with this automated technique. Results: Patient-matching improved the percentage of patients eligible for dose-escalation from 40% to 63% (p=4.7e-4, t-test). Using a commercial optimizer augmented with patient-matching, we demonstrated a case where patient-matching improved the toxicity-profile such that dose-escalation would have been possible; this plan was rapidly achieved using patientmatching software. In this patient, all lower-dose constraints were met with both the denovo and patient-matching plan. In the patient-matching plan, maximum dose to the rectum was 8385cGy, while the denovo plan failed to meet the maximum rectal constraint at 8571c

  19. Regulation of aggregate size and pattern by adenosine and caffeine in cellular slime molds

    Directory of Open Access Journals (Sweden)

    Jaiswal Pundrik

    2012-01-01

    Full Text Available Abstract Background Multicellularity in cellular slime molds is achieved by aggregation of several hundreds to thousands of cells. In the model slime mold Dictyostelium discoideum, adenosine is known to increase the aggregate size and its antagonist caffeine reduces the aggregate size. However, it is not clear if the actions of adenosine and caffeine are evolutionarily conserved among other slime molds known to use structurally unrelated chemoattractants. We have examined how the known factors affecting aggregate size are modulated by adenosine and caffeine. Result Adenosine and caffeine induced the formation of large and small aggregates respectively, in evolutionarily distinct slime molds known to use diverse chemoattractants for their aggregation. Due to its genetic tractability, we chose D. discoideum to further investigate the factors affecting aggregate size. The changes in aggregate size are caused by the effect of the compounds on several parameters such as cell number and size, cell-cell adhesion, cAMP signal relay and cell counting mechanisms. While some of the effects of these two compounds are opposite to each other, interestingly, both compounds increase the intracellular glucose level and strengthen cell-cell adhesion. These compounds also inhibit the synthesis of cAMP phosphodiesterase (PdsA, weakening the relay of extracellular cAMP signal. Adenosine as well as caffeine rescue mutants impaired in stream formation (pde4- and pdiA- and colony size (smlA- and ctnA- and restore their parental aggregate size. Conclusion Adenosine increased the cell division timings thereby making large number of cells available for aggregation and also it marginally increased the cell size contributing to large aggregate size. Reduced cell division rates and decreased cell size in the presence of caffeine makes the aggregates smaller than controls. Both the compounds altered the speed of the chemotactic amoebae causing a variation in aggregate size

  20. Describing Myxococcus xanthus Aggregation Using Ostwald Ripening Equations for Thin Liquid Films

    OpenAIRE

    Fatmagül Bahar; Philip C. Pratt-Szeliga; Stuart Angus; Jiaye Guo; Welch, Roy D.

    2014-01-01

    When starved, a swarm of millions of Myxococcus xanthus cells coordinate their movement from outward swarming to inward coalescence. The cells then execute a synchronous program of multicellular development, arranging themselves into dome shaped aggregates. Over the course of development, about half of the initial aggregates disappear, while others persist and mature into fruiting bodies. This work seeks to develop a quantitative model for aggregation that accurately simulates which will disa...