WorldWideScience

Sample records for period prp paradigm

  1. Modularity beyond Perception: Evidence from the PRP Paradigm

    Science.gov (United States)

    Magen, Hagit; Cohen, Asher

    2010-01-01

    The Dimension Action (DA) model asserts that the visual system is modular, and that each task involves multiple-response mechanisms rather than a unitary-response selection mechanism. The model has been supported by evidence from single-task interference paradigms. We use the psychological refractory period paradigm and show that dual-task…

  2. Exceptions to the PRP Effect? A Comparison of Prepared and Unconditioned Reflexes

    Science.gov (United States)

    Janczyk, Markus; Pfister, Roland; Wallmeier, Gloria; Kunde, Wilfried

    2014-01-01

    Psychological research has documented again and again marked performance decrements whenever humans perform 2 or more tasks at the same time. In fact, the available evidence seems to suggest that any type of behavior is subject to such limitations. The present experiments employed the psychological refractory period (PRP) paradigm to identify a…

  3. Backward Response-Level Crosstalk in the Psychological Refractory Period Paradigm

    Science.gov (United States)

    Miller, Jeff; Alderton, Mark

    2006-01-01

    Bottleneck models of psychological refractory period (PRP) tasks suggest that a Task 1 response should be unaffected by the Task 2 response in the same trial, because selection of the former finishes before selection of the latter begins. Contrary to this conception, the authors found backward response-level crosstalk effects in which Task 2…

  4. On the importance of Task 1 and error performance measures in PRP dual-task studies

    Science.gov (United States)

    Strobach, Tilo; Schütz, Anja; Schubert, Torsten

    2015-01-01

    The psychological refractory period (PRP) paradigm is a dominant research tool in the literature on dual-task performance. In this paradigm a first and second component task (i.e., Task 1 and Task 2) are presented with variable stimulus onset asynchronies (SOAs) and priority to perform Task 1. The main indicator of dual-task impairment in PRP situations is an increasing Task 2-RT with decreasing SOAs. This impairment is typically explained with some task components being processed strictly sequentially in the context of the prominent central bottleneck theory. This assumption could implicitly suggest that processes of Task 1 are unaffected by Task 2 and bottleneck processing, i.e., decreasing SOAs do not increase reaction times (RTs) and error rates of the first task. The aim of the present review is to assess whether PRP dual-task studies included both RT and error data presentations and statistical analyses and whether studies including both data types (i.e., RTs and error rates) show data consistent with this assumption (i.e., decreasing SOAs and unaffected RTs and/or error rates in Task 1). This review demonstrates that, in contrast to RT presentations and analyses, error data is underrepresented in a substantial number of studies. Furthermore, a substantial number of studies with RT and error data showed a statistically significant impairment of Task 1 performance with decreasing SOA. Thus, these studies produced data that is not primarily consistent with the strong assumption that processes of Task 1 are unaffected by Task 2 and bottleneck processing in the context of PRP dual-task situations; this calls for a more careful report and analysis of Task 1 performance in PRP studies and for a more careful consideration of theories proposing additions to the bottleneck assumption, which are sufficiently general to explain Task 1 and Task 2 effects. PMID:25904890

  5. On the importance of Task 1 and error performance measures in PRP dual-task studies.

    Science.gov (United States)

    Strobach, Tilo; Schütz, Anja; Schubert, Torsten

    2015-01-01

    The psychological refractory period (PRP) paradigm is a dominant research tool in the literature on dual-task performance. In this paradigm a first and second component task (i.e., Task 1 and Task 2) are presented with variable stimulus onset asynchronies (SOAs) and priority to perform Task 1. The main indicator of dual-task impairment in PRP situations is an increasing Task 2-RT with decreasing SOAs. This impairment is typically explained with some task components being processed strictly sequentially in the context of the prominent central bottleneck theory. This assumption could implicitly suggest that processes of Task 1 are unaffected by Task 2 and bottleneck processing, i.e., decreasing SOAs do not increase reaction times (RTs) and error rates of the first task. The aim of the present review is to assess whether PRP dual-task studies included both RT and error data presentations and statistical analyses and whether studies including both data types (i.e., RTs and error rates) show data consistent with this assumption (i.e., decreasing SOAs and unaffected RTs and/or error rates in Task 1). This review demonstrates that, in contrast to RT presentations and analyses, error data is underrepresented in a substantial number of studies. Furthermore, a substantial number of studies with RT and error data showed a statistically significant impairment of Task 1 performance with decreasing SOA. Thus, these studies produced data that is not primarily consistent with the strong assumption that processes of Task 1 are unaffected by Task 2 and bottleneck processing in the context of PRP dual-task situations; this calls for a more careful report and analysis of Task 1 performance in PRP studies and for a more careful consideration of theories proposing additions to the bottleneck assumption, which are sufficiently general to explain Task 1 and Task 2 effects.

  6. On the importance of Task 1 and error performance measures in PRP dual-task studies

    Directory of Open Access Journals (Sweden)

    Tilo eStrobach

    2015-04-01

    Full Text Available The Psychological Refractory Period (PRP paradigm is a dominant research tool in the literature on dual-task performance. In this paradigm a first and second component task (i.e., Task 1 and 2 are presented with variable stimulus onset asynchronies (SOAs and priority to perform Task 1. The main indicator of dual-task impairment in PRP situations is an increasing Task 2-RT with decreasing SOAs. This impairment is typically explained with some task components being processed strictly sequentially in the context of the prominent central bottleneck theory. This assumption could implicitly suggest that processes of Task 1 are unaffected by Task 2 and bottleneck processing, i.e. decreasing SOAs do not increase RTs and error rates of the first task. The aim of the present review is to assess whether PRP dual-task studies included both RT and error data presentations and statistical analyses and whether studies including both data types (i.e., RTs and error rates show data consistent with this assumption (i.e., decreasing SOAs and unaffected RTs and/ or error rates in Task 1. This review demonstrates that, in contrast to RT presentations and analyses, error data is underrepresented in a substantial number of studies. Furthermore, a substantial number of studies with RT and error data showed a statistically significant impairment of Task 1 performance with decreasing SOA. Thus, these studies produced data that is not primarily consistent with the strong assumption that processes of Task 1 are unaffected by Task 2 and bottleneck processing in the context of PRP dual-task situations; this calls for a more careful report and analysis of Task 1 performance in PRP studies and for a more careful consideration of theories proposing additions to the bottleneck assumption, which are sufficiently general to explain Task 1 and Task 2 effects.

  7. Long-term trends in invasive Haemophilus influenzae type B disease among indigenous Australian children following use of PRP-OMP and PRP-T vaccines.

    Science.gov (United States)

    Menzies, Robert Ian; Bremner, Kyla Margaret; Wang, Han; Beard, Frank Hudson; McIntyre, Peter Bruce

    2015-06-01

    Among indigenous populations with high incidence and early onset of invasive Haemophilus influenzae type b (Hib) disease, PRP-OMP vaccines are used in the United States and PRP-T vaccines in Canada. In Australia, PRP-OMP vaccines were exclusively used in indigenous children from 1993 until they were replaced by PRP-T between late 2005 and 2009. Analytic descriptive study of 20 years of enhanced surveillance data (1993-2013) for invasive Hib disease in Australian children PRP-OMP period (1993-1996) to 6.2 (95% CI: 4.0, 9.2) and 4.7 (95% CI: 1.7, 10.3) in the later PRP-OMP (1996-2009) and PRP-T periods (2009-2013), respectively. The indigenous:nonindigenous incidence rate ratio increased to 43 (95% CI: 16, 145) and 58 (95% CI: 7, 2660) in the later PRP-OMP and PRP-T periods, respectively, more than 10-fold higher than in lesser-incidence Australian regions. We found no change in Hib incidence among indigenous Australian children living in high-incidence regions in the first 4 years following a change to PRP-T-containing combination vaccines. This may be of relevance to North American indigenous populations characterized by suboptimal living conditions and young age of onset for whom PRP-OMP continues to be recommended, such as Alaska Natives.

  8. Quantitating PrP Polymorphisms Present in Prions from Heterozygous Scrapie-Infected Sheep.

    Science.gov (United States)

    Silva, Christopher J; Erickson-Beltran, Melissa L; Hui, Colleen; Badiola, Juan José; Nicholson, Eric M; Requena, Jesús R; Bolea, Rosa

    2017-01-03

    Scrapie is a prion (PrP Sc ) disease of sheep. The incubation period of sheep scrapie is strongly influenced by polymorphisms at positions 136, 154, and 171 of a sheep's normal cellular prion protein (PrP C ). Chymotrypsin was used to digest sheep recombinant PrP to identify a set of characteristic peptides [M 132 LGSXMSRPL 141 (X = A or V), Y 153 XENMY 158 (X,= H or R), and Y 166 RPVDXY 172 (X = H, K, Q, or R)] that could be used to detect and quantitate polymorphisms at positions 136, 154, and 171 of sheep PrP C or PrP Sc . These peptides were used to develop a multiple reaction monitoring method (MRM) to detect the amounts of a particular polymorphism in a sample of PrP Sc isolated from sheep heterozygous for their PrP C proteins. The limit of detection for these peptides was less than 50 attomole. Spinal cord tissue from heterozygous (ARQ/VRQ or ARH/ARQ) scrapie-infected Rasa Aragonesa sheep was analyzed using this MRM method. Both sets of heterozygotes show the presence of both polymorphisms in PrP Sc . This was true for samples containing both proteinase K (PK)-sensitive and PK-resistant PrP Sc and samples containing only the PK-resistant PrP Sc . These results show that heterozygous animals contain PrP Sc that is composed of significant amounts of both PrP polymorphisms.

  9. Decision Making during the Psychological Refractory Period

    NARCIS (Netherlands)

    Zylberberg, Ariel; Ouellette, Brian; Sigman, Mariano; Roelfsema, Pieter R.

    2012-01-01

    In spite of its massively parallel architecture [1], the human brain is fundamentally limited if required to perform two tasks at the same time [2, 3]. This limitation can be studied with the psychological refractory period (PRP) paradigm, where two stimuli that require speeded responses occur in

  10. Hyperuricemic PRP in Tendon Cells

    Directory of Open Access Journals (Sweden)

    I. Andia

    2014-01-01

    Full Text Available Platelet-rich plasma (PRP is injected within tendons to stimulate healing. Metabolic alterations such as the metabolic syndrome, diabetes, or hyperuricemia could hinder the therapeutic effect of PRP. We hypothesise that tendon cells sense high levels of uric acid and this could modify their response to PRP. Tendon cells were treated with allogeneic PRPs for 96 hours. Hyperuricemic PRP did not hinder the proliferative actions of PRP. The gene expression pattern of inflammatory molecules in response to PRP showed absence of IL-1b and COX1 and modest expression of IL6, IL8, COX2, and TGF-b1. IL8 and IL6 proteins were secreted by tendon cells treated with PRP. The synthesis of IL6 and IL8 proteins induced by PRP is decreased significantly in the presence of hyperuricemia (P = 0.017 and P = 0.012, resp.. Concerning extracellular matrix, PRP-treated tendon cells displayed high type-1 collagen, moderate type-3 collagen, decorin, and hyaluronan synthase-2 expression and modest expression of scleraxis. Hyperuricemia modified the expression pattern of extracellular matrix proteins, upregulating COL1 (P = 0.036 and COMP (P = 0.012 and downregulating HAS2 (P = 0.012. Positive correlations between TGF-b1 and type-1 collagen (R = 0.905, P = 0.002 and aggrecan (R = 0.833, P = 0.010 and negative correlations between TGF-b1 and IL6 synthesis (R = −0.857, P = 0.007 and COX2 (R = −0.810, P = 0.015 were found.

  11. Can PRP effectively treat injured tendons?

    Science.gov (United States)

    Wang, James H-C

    2014-01-01

    PRP is widely used to treat tendon and other tissue injuries in orthopaedics and sports medicine; however, the efficacy of PRP treatment on injured tendons is highly controversial. In this commentary, I reason that there are many PRP- and patient-related factors that influence the outcomes of PRP treatment on injured tendons. Therefore, more basic science studies are needed to understand the mechanism of PRP on injured tendons. Finally, I suggest that better understanding of the PRP action mechanism will lead to better use of PRP for the effective treatment of tendon injuries in clinics.

  12. Phase diagram of Pr-P system

    International Nuclear Information System (INIS)

    Mironov, K.E.

    1981-01-01

    An area of the Pr-P system, adjoining to the Pr ordinate, is plotted up by the DTA method. Presence of P solid solution in Pr is established. Data on thermal stability of PrP, PrP 2 , PrP 5 and PrP 7 are generalized. The diagram of phase transformations in Pr-P system is plotted up proceeding from the whole complex of the data, presented. A supposition is made on a possible formation of solid solutions between the highest polyphosphide and phosphorus [ru

  13. Effects of Frequency and Motion Paradigm on Perception of Tilt and Translation During Periodic Linear Acceleration

    Science.gov (United States)

    Beaton, K. H.; Holly, J. E.; Clement, G. R.; Wood, Scott J.

    2009-01-01

    Previous studies have demonstrated an effect of frequency on the gain of tilt and translation perception. Results from different motion paradigms are often combined to extend the stimulus frequency range. For example, Off-Vertical Axis Rotation (OVAR) and Variable Radius Centrifugation (VRC) are useful to test low frequencies of linear acceleration at amplitudes that would require impractical sled lengths. The purpose of this study was to compare roll-tilt and lateral translation motion perception in 12 healthy subjects across four paradigms: OVAR, VRC, sled translation and rotation about an earth-horizontal axis. Subjects were oscillated in darkness at six frequencies from 0.01875 to 0.6 Hz (peak acceleration equivalent to 10 deg, less for sled motion below 0.15 Hz). Subjects verbally described the amplitude of perceived tilt and translation, and used a joystick to indicate the direction of motion. Consistent with previous reports, tilt perception gain decreased as a function of stimulus frequency in the motion paradigms without concordant canal tilt cues (OVAR, VRC and Sled). Translation perception gain was negligible at low stimulus frequencies and increased at higher frequencies. There were no significant differences between the phase of tilt and translation, nor did the phase significantly vary across stimulus frequency. There were differences in perception gain across the different paradigms. Paradigms that included actual tilt stimuli had the larger tilt gains, and paradigms that included actual translation stimuli had larger translation gains. In addition, the frequency at which there was a crossover of tilt and translation gains appeared to vary across motion paradigm between 0.15 and 0.3 Hz. Since the linear acceleration in the head lateral plane was equivalent across paradigms, differences in gain may be attributable to the presence of linear accelerations in orthogonal directions and/or cognitive aspects based on the expected motion paths.

  14. Enhanced healing of mitomycin C-treated healing-impaired wounds in rats with PRP-containing fragmin/protamine microparticles (PRP&F/P MPs).

    Science.gov (United States)

    Takikawa, Megumi; Ishihara, Masayuki; Takabayashi, Yuki; Sumi, Yuki; Takikawa, Makoto; Yoshida, Ryuichi; Nakamura, Shingo; Hattori, Hidemi; Yanagibayashi, Satoshi; Yamamoto, Naoto; Kiyosawa, Tomoharu

    2015-04-13

    The purpose of this study was to evaluate the accelerating effects of platelet-rich plasma-containing (PRP&) fragmin/protamine microparticles (F/P MPs) for repairing mitomycin C-treated healing-impaired wounds. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL-staining) showed that apoptosis of dermal fibroblast cells (DFCs) and epidermal keratinocyte cells (EKCs) were significantly induced in the skin of the mitomycin C-treated rats. Full-thickness skin defects were made on the back of rats and mitomycin C was applied on the wounds to prepare a healing-impaired wound. After washing out the mitomycin C, saline (control), F/P MPs alone, PRP alone, and PRP&F/P MPs were injected around the wounds. The rats were later euthanised and histological sections of the wounds were then prepared at indicated time periods after the treatment. These results indicated the numbers of large, medium, and small capillary lumens 7 days after injection of PRP&F/P MPs were significantly higher than those after injection of PRP or F/P MPs alone. Furthermore, epithelium and granulation tissue formations were significantly stimulated in the healing-impaired wounds treated with PRP&F/P MPs 3, 7 and 14 days after injection of PRP&F/P MPs.

  15. Ionic mechanisms of action of prion protein fragment PrP(106-126) in rat basal forebrain neurons.

    Science.gov (United States)

    Alier, Kwai; Li, Zongming; Mactavish, David; Westaway, David; Jhamandas, Jack H

    2010-08-01

    Prion diseases are neurodegenerative disorders that are characterized by the presence of the misfolded prion protein (PrP). Neurotoxicity in these diseases may result from prion-induced modulation of ion channel function, changes in neuronal excitability, and consequent disruption of cellular homeostasis. We therefore examined PrP effects on a suite of potassium (K(+)) conductances that govern excitability of basal forebrain neurons. Our study examined the effects of a PrP fragment [PrP(106-126), 50 nM] on rat neurons using the patch clamp technique. In this paradigm, PrP(106-126) peptide, but not the "scrambled" sequence of PrP(106-126), evoked a reduction of whole-cell outward currents in a voltage range between -30 and +30 mV. Reduction of whole-cell outward currents was significantly attenuated in Ca(2+)-free external media and also in the presence of iberiotoxin, a blocker of calcium-activated potassium conductance. PrP(106-126) application also evoked a depression of the delayed rectifier (I(K)) and transient outward (I(A)) potassium currents. By using single cell RT-PCR, we identified the presence of two neuronal chemical phenotypes, GABAergic and cholinergic, in cells from which we recorded. Furthermore, cholinergic and GABAergic neurons were shown to express K(v)4.2 channels. Our data establish that the central region of PrP, defined by the PrP(106-126) peptide used at nanomolar concentrations, induces a reduction of specific K(+) channel conductances in basal forebrain neurons. These findings suggest novel links between PrP signalling partners inferred from genetic experiments, K(+) channels, and PrP-mediated neurotoxicity.

  16. PrP Knockout Cells Expressing Transmembrane PrP Resist Prion Infection.

    Science.gov (United States)

    Marshall, Karen E; Hughson, Andrew; Vascellari, Sarah; Priola, Suzette A; Sakudo, Akikazu; Onodera, Takashi; Baron, Gerald S

    2017-01-15

    Glycosylphosphatidylinositol (GPI) anchoring of the prion protein (PrP C ) influences PrP C misfolding into the disease-associated isoform, PrP res , as well as prion propagation and infectivity. GPI proteins are found in cholesterol- and sphingolipid-rich membrane regions called rafts. Exchanging the GPI anchor for a nonraft transmembrane sequence redirects PrP C away from rafts. Previous studies showed that nonraft transmembrane PrP C variants resist conversion to PrP res when transfected into scrapie-infected N2a neuroblastoma cells, likely due to segregation of transmembrane PrP C and GPI-anchored PrP res in distinct membrane environments. Thus, it remained unclear whether transmembrane PrP C might convert to PrP res if seeded by an exogenous source of PrP res not associated with host cell rafts and without the potential influence of endogenous expression of GPI-anchored PrP C To further explore these questions, constructs containing either a C-terminal wild-type GPI anchor signal sequence or a nonraft transmembrane sequence containing a flexible linker were expressed in a cell line derived from PrP knockout hippocampal neurons, NpL2. NpL2 cells have physiological similarities to primary neurons, representing a novel and advantageous model for studying transmissible spongiform encephalopathy (TSE) infection. Cells were infected with inocula from multiple prion strains and in different biochemical states (i.e., membrane bound as in brain microsomes from wild-type mice or purified GPI-anchorless amyloid fibrils). Only GPI-anchored PrP C supported persistent PrP res propagation. Our data provide strong evidence that in cell culture GPI anchor-directed membrane association of PrP C is required for persistent PrP res propagation, implicating raft microdomains as a location for conversion. Mechanisms of prion propagation, and what makes them transmissible, are poorly understood. Glycosylphosphatidylinositol (GPI) membrane anchoring of the prion protein (PrP C

  17. A shared cortical bottleneck underlying Attentional Blink and Psychological Refractory Period.

    Science.gov (United States)

    Marti, Sébastien; Sigman, Mariano; Dehaene, Stanislas

    2012-02-01

    Doing two things at once is difficult. When two tasks have to be performed within a short interval, the second is sharply delayed, an effect called the Psychological Refractory Period (PRP). Similarly, when two successive visual targets are briefly flashed, people may fail to detect the second target (Attentional Blink or AB). Although AB and PRP are typically studied in very different paradigms, a recent detailed neuromimetic model suggests that both might arise from the same serial stage during which stimuli gain access to consciousness and, as a result, can be arbitrarily routed to any other appropriate processor. Here, in agreement with this model, we demonstrate that AB and PRP can be obtained on alternate trials of the same cross-modal paradigm and result from limitations in the same brain mechanisms. We asked participants to respond as fast as possible to an auditory target T1 and then to a visual target T2 embedded in a series of distractors, while brain activity was recorded with magneto-encephalography (MEG). For identical stimuli, we observed a mixture of blinked trials, where T2 was entirely missed, and PRP trials, where T2 processing was delayed. MEG recordings showed that PRP and blinked trials underwent identical sensory processing in visual occipito-temporal cortices, even including the non-conscious separation of targets from distractors. However, late activations in frontal cortex (>350 ms), strongly influenced by the speed of task-1 execution, were delayed in PRP trials and absent in blinked trials. Our findings suggest that PRP and AB arise from similar cortical stages, can occur with the same exact stimuli, and are merely distinguished by trial-by-trial fluctuations in task processing. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. PRP and Articular Cartilage: A Clinical Update

    Science.gov (United States)

    Rossi, Roberto; Castoldi, Filippo; Michielon, Gianni

    2015-01-01

    The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis. Recent evidences in literature have shown that PRP may be helpful both as an adjuvant for surgical treatment of cartilage defects and as a therapeutic tool by intra-articular injection in patients affected by osteoarthritis. In this review, the authors introduce the trophic and anti-inflammatory properties of PRP and the different products of the available platelet concentrates. Then, in a complex scenario made of a great number of clinical variables, they resume the current literature on the PRP applications in cartilage surgery as well as the use of intra-articular PRP injections for the conservative treatment of cartilage degenerative lesions and osteoarthritis in humans, available as both case series and comparative studies. The result of this review confirms the fascinating biological role of PRP, although many aspects yet remain to be clarified and the use of PRP in a clinical setting has to be considered still exploratory. PMID:26075244

  19. PRP and Articular Cartilage: A Clinical Update

    Directory of Open Access Journals (Sweden)

    Antonio Marmotti

    2015-01-01

    Full Text Available The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis. Recent evidences in literature have shown that PRP may be helpful both as an adjuvant for surgical treatment of cartilage defects and as a therapeutic tool by intra-articular injection in patients affected by osteoarthritis. In this review, the authors introduce the trophic and anti-inflammatory properties of PRP and the different products of the available platelet concentrates. Then, in a complex scenario made of a great number of clinical variables, they resume the current literature on the PRP applications in cartilage surgery as well as the use of intra-articular PRP injections for the conservative treatment of cartilage degenerative lesions and osteoarthritis in humans, available as both case series and comparative studies. The result of this review confirms the fascinating biological role of PRP, although many aspects yet remain to be clarified and the use of PRP in a clinical setting has to be considered still exploratory.

  20. Portable Radiation Package (PRP) Instrument Handbook

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, R Michael [Remote Measurements and Research Company, Seattle, WA (United States)

    2017-08-03

    The Portable Radiation Package (PRP) was developed to provide basic radiation information in locations such as ships at sea where proper exposure is remote and difficult, the platform is in motion, and azimuth alignment is not fixed. Development of the PRP began at Brookhaven National Laboratory (BNL) in the mid-1990s and versions of it were deployed on ships in the U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Climate Research Facility’s Nauru-99 project. The PRP was deployed on ships in support of the National Aeronautics and Space Administration (NASA) Sensor Intercomparison for Marine Biological and Interdisciplinary Ocean Studies (SIMBIOS) program. Over the years the measurements have remained the same while the post-processing data analysis, especially for the FRSR, has evolved. This document describes the next-generation Portable Radiation Package (PRP2) that was developed for the DOE ARM Facility, under contract no. 9F-31462 from Argonne National Laboratory (ANL). The PRP2 has the same scientific principles that were well validated in prior studies, but has upgraded electronic hardware. The PRP2 approach is completely modular, both in hardware and software. Each sensor input is treated as a separate serial stream into the data collection computer. In this way the operator has complete access to each component of the system for purposes of error checking, calibration, and maintenance. The resulting system is more reliable, easier to install in complex situations, and more amenable to upgrade.

  1. Mitigating the effects of in-vehicle distractions through use of the Psychological Refractory Period paradigm.

    Science.gov (United States)

    Hibberd, Daryl L; Jamson, Samantha L; Carsten, Oliver M J

    2013-01-01

    Modern driving involves frequent and potentially detrimental interactions with distracting in-vehicle tasks. Distraction has been shown to slow brake reaction time and decrease lateral and longitudinal vehicle control. It is likely that these negative effects will become more prevalent in the future as advances are made in the functionality, availability, and number of in-vehicle systems. This paper addresses this problem by considering ways to manage in-vehicle task presentation to mitigate their distracting effects. A driving simulator experiment using 48 participants was performed to investigate the existence of the Psychological Refractory Period in the driving context and its effect on braking performance. Drivers were exposed to lead vehicle braking events in isolation (single-task) and with a preceding surrogate in-vehicle task (dual-task). In dual-task scenarios, the time interval between the in-vehicle and braking tasks was manipulated. Brake reaction time increased when drivers were distracted. The in-vehicle task interfered with the performance of the braking task in a manner that was dependent on the interval between the two tasks, with slower reactions following a shorter inter-task interval. This is the Psychological Refractory Period effect. These results have implications for driver safety during in-vehicle distraction. The findings are used to develop recommendations regarding the timing of in-vehicle task presentation so as to reduce their potentially damaging effects on braking performance. In future, these guidelines could be incorporated into a driver workload management system to minimise the opportunity for a driver to be distracted from the ongoing driving task. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Prion protein (PrP) gene-knockout cell lines: insight into functions of the PrP

    OpenAIRE

    Sakudo, Akikazu; Onodera, Takashi

    2015-01-01

    Elucidation of prion protein (PrP) functions is crucial to fully understand prion diseases. A major approach to studying PrP functions is the use of PrP gene-knockout (Prnp ?/?) mice. So far, six types of Prnp ?/? mice have been generated, demonstrating the promiscuous functions of PrP. Recently, other PrP family members, such as Doppel and Shadoo, have been found. However, information obtained from comparative studies of structural and functional analyses of these PrP family proteins do not ...

  3. PRP: a FORTRAN IV interactive plotting program

    Science.gov (United States)

    Andrew, A. S.; Linde, J.

    A computer program, PRP, has been designed to plot any arithmetic combination selected from a set of major and trace element data on a y- x graph. y and x are defined and entered as a program string (y, x) which is interpreted sequentially. Operators ( +, -, ∗, /, ( unary) , square root, log 10, In c, antilog 10, exponential, integer, absolute value, (,),,) and integer or real numbers may be included. Axis lengths and scales are determined by the user. Five different plotting symbols are available.

  4. Periodontal tissue regeneration with PRP incorporated gelatin hydrogel sponges.

    Science.gov (United States)

    Nakajima, Dai; Tabata, Yasuhiko; Sato, Soh

    2015-10-20

    Gelatin hydrogels have been designed and prepared for the controlled release of the transforming growth factor (TGF-b1) and the platelet-derived growth factor (PDGF-BB). PRP (Platelet rich plasma) contains many growth factors including the PDGF and TGF-b1. The objective of this study was to evaluate the regeneration of periodontal tissue following the controlled release of growth factors in PRP. For the periodontal ligament cells and osteoblast, PRP of different concentrations was added. The assessment of DNA, mitochondrial activity and ALP activity were measured. To evaluate the TGF-β1 release from PRP incorporated gelatin sponge, amounts of TGF-β1 in each supernatant sample were determined by the ELISA. Transplantation experiments to prepare a bone defect in a rat alveolar bone were an implanted gelatin sponge incorporated with different concentration PRP. In DNA assay and MTT assay, after the addition of PRP to the periodontal ligament cells and osteoblast, the cell count and mitochondrial activity had increased the most in the group with the addition of 5  ×  PRP. In the ALP assay, after the addition of PRP to the periodontal ligament cells, the cell activity had increased the most in the group with the addition of 3  ×  PRP. In the transplantation, the size of the bone regenerated in the defect with 3  ×  PRP incorporated gelatin sponge was larger than that of the other group.

  5. Periodontal tissue regeneration with PRP incorporated gelatin hydrogel sponges

    International Nuclear Information System (INIS)

    Nakajima, Dai; Tabata, Yasuhiko; Sato, Soh

    2015-01-01

    Gelatin hydrogels have been designed and prepared for the controlled release of the transforming growth factor (TGF-b1) and the platelet-derived growth factor (PDGF-BB). PRP (Platelet rich plasma) contains many growth factors including the PDGF and TGF-b1. The objective of this study was to evaluate the regeneration of periodontal tissue following the controlled release of growth factors in PRP. For the periodontal ligament cells and osteoblast, PRP of different concentrations was added. The assessment of DNA, mitochondrial activity and ALP activity were measured. To evaluate the TGF-β1 release from PRP incorporated gelatin sponge, amounts of TGF-β1 in each supernatant sample were determined by the ELISA. Transplantation experiments to prepare a bone defect in a rat alveolar bone were an implanted gelatin sponge incorporated with different concentration PRP. In DNA assay and MTT assay, after the addition of PRP to the periodontal ligament cells and osteoblast, the cell count and mitochondrial activity had increased the most in the group with the addition of 5  ×  PRP. In the ALP assay, after the addition of PRP to the periodontal ligament cells, the cell activity had increased the most in the group with the addition of 3  ×  PRP. In the transplantation, the size of the bone regenerated in the defect with 3  ×  PRP incorporated gelatin sponge was larger than that of the other group. (paper)

  6. Prion protein (PrP) gene-knockout cell lines: insight into functions of the PrP

    Science.gov (United States)

    Sakudo, Akikazu; Onodera, Takashi

    2015-01-01

    Elucidation of prion protein (PrP) functions is crucial to fully understand prion diseases. A major approach to studying PrP functions is the use of PrP gene-knockout (Prnp−/−) mice. So far, six types of Prnp−/− mice have been generated, demonstrating the promiscuous functions of PrP. Recently, other PrP family members, such as Doppel and Shadoo, have been found. However, information obtained from comparative studies of structural and functional analyses of these PrP family proteins do not fully reveal PrP functions. Recently, varieties of Prnp−/− cell lines established from Prnp−/− mice have contributed to the analysis of PrP functions. In this mini-review, we focus on Prnp−/− cell lines and summarize currently available Prnp−/− cell lines and their characterizations. In addition, we introduce the recent advances in the methodology of cell line generation with knockout or knockdown of the PrP gene. We also discuss how these cell lines have provided valuable insights into PrP functions and show future perspectives. PMID:25642423

  7. The relative kicking frequency of infants born full-term and preterm during learning and short-term and long-term memory periods of the mobile paradigm.

    Science.gov (United States)

    Heathcock, Jill C; Bhat, Anjana N; Lobo, Michele A; Galloway, James C

    2005-01-01

    Infants born preterm differ in their spontaneous kicking, as well as their learning and memory abilities in the mobile paradigm, compared with infants born full-term. In the mobile paradigm, a supine infant's ankle is tethered to a mobile so that leg kicks cause a proportional amount of mobile movement. The purpose of this study was to investigate the relative kicking frequency of the tethered (right) and nontethered (left) legs in these 2 groups of infants. Ten infants born full-term and 10 infants born preterm (infants participated in the study. The relative kicking frequencies of the tethered and nontethered legs were analyzed during learning and short-term and long-term memory periods of the mobile paradigm. Infants born full-term showed an increase in the relative kicking frequency of the tethered leg during the learning period and the short-term memory period but not for the long-term memory period. Infants born preterm did not show a change in kicking pattern for learning or memory periods, and consistently kicked both legs in relatively equal amounts. Infants born full-term adapted their baseline kicking frequencies in a task-specific manner to move the mobile and then retained this adaptation for the short-term memory period. In contrast, infants born preterm showed no adaptation, suggesting a lack of purposeful leg control. This lack of control may reflect a general decrease in the ability of infants born preterm to use their limb movements to interact with their environment. As such, the mobile paradigm may be clinically useful in the early assessment and intervention of infants born preterm and at risk for future impairment.

  8. Experimental Models of Inherited PrP Prion Diseases.

    Science.gov (United States)

    Watts, Joel C; Prusiner, Stanley B

    2017-11-01

    The inherited prion protein (PrP) prion disorders, which include familial Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia, constitute ∼10%-15% of all PrP prion disease cases in humans. Attempts to generate animal models of these disorders using transgenic mice expressing mutant PrP have produced variable results. Although many lines of mice develop spontaneous signs of neurological illness with accompanying prion disease-specific neuropathological changes, others do not. Furthermore, demonstrating the presence of protease-resistant PrP species and prion infectivity-two of the hallmarks of the PrP prion disorders-in the brains of spontaneously sick mice has proven particularly challenging. Here, we review the progress that has been made toward developing accurate mouse models of the inherited PrP prion disorders. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  9. PRP as an Adjunct to Rotator Cuff Tendon Repair.

    Science.gov (United States)

    Barber, F Alan

    2018-06-01

    Arthroscopic rotator cuff repair is a commonly performed repair. Technical developments provide surgeons the tools to create biomechanically robust repairs. How can the biological response mirror the strong and stable surgery? Platelet-rich plasma (PRP) is a supraphysiological platelet concentration which may positively augment rotator cuff healing. Not all PRPs are the same. High leukocyte levels and thrombin activation may be detrimental to tendon healing. Thrombin activation triggers an immediate release of growth factors and may actually inhibit some parts of the healing response. Clear differences exist between liquid PRP (products released within hours after activation) and solid fibrin PRP which slowly releases factors over days. The heterogenicity data and grouping liquid and solid PRP together make systematic reviews confusing. Solid PRP fibrin constructs are often associated with increased tendon healing. PRP fibrin matrix offers the greatest promise for improving clinical success after rotator cuff tendon repair.

  10. PRP in OA knee - update, current confusions and future options.

    Science.gov (United States)

    Dhillon, Mandeep S; Patel, Sandeep; John, Rakesh

    2017-01-01

    Positive results have been uniformly observed by various researchers for platelet-rich plasma (PRP) in early osteoarthritis (OA) knee in the past few years. PRP has clearly demonstrated its supremacy in comparison to hyaluronic acid (HA) and placebo in various clinical trials and is undoubtedly the best option available for symptomatic treatment in early OA. The release of growth factors from PRP occurs immediately and lasts for around three weeks and the clinical effect tends to wane down by the end of the year. Prolonged and sustained release of growth factors from platelets could possibly help in much better biological healing and sustained clinical effects. PRP in combination with biocompatible carriers could be one way of achieving this. Gelatin hydrogel PRP and chitosan PRP seem to be promising based on early in vitro studies and animal studies. PRP in combination with hyaluronic acid also seems to be additive. This article intends to discuss the present status of the PRP, confusions surrounding its use, upcoming trends and ideas for improvising PRP for use early OA knees based on available evidence. © The Authors, published by EDP Sciences, 2017.

  11. Split face comparative study of microneedling with PRP versus microneedling with vitamin C in treating atrophic post acne scars

    Directory of Open Access Journals (Sweden)

    Simran Chawla

    2014-01-01

    Full Text Available Introduction: Acne scars are largely preventable complications of acne. 95% of the scars occur over the face thus impacting the quality of life. Correction of scars is the priority for acne patients. Materials and Methods: Thirty patients with post acne atrophic facial scars attending the OPD during the period from April to October 2013 were offered four sittings of microneedling with PRP on one side and microneedling with vitamin C on other side of the face at an interval of 1 month. Results: Twenty-seven out of the total 30 patients completed the treatment schedule. Two patients were lost to follow up and one dropped out of the study due to severe PIH. Mean age of the patients was 27.5 years. Out of 30 patients, 23 achieved reduction in scarring by one or two grades. Excellent response was seen in five (18.5% patients with platelet-rich plasma (PRP as compared to two (7% patients who received treatment with vitamin C according to physician′s assessment. As far as up gradation by 1 score is considered, i.e., good response, it was similar in both cases. Vitamin C did not prove to be as efficacious as PRP since 10 (37% patients had poor response in vitamin C-treated area compared to only 6 (22.2% patients who underwent PRP therapy, but vitamin C proved to be efficacious in dealing with post inflammatory hyper-pigmentation secondary to acne. Patients were more satisfied with PRP as compared to vitamin C. The results were evaluated and statistical analysis was done using SPSS 16.0.2. Conclusions: Overall results were better with microneedling and PRP. Vitamin C combined with microneedling also showed improvement with respect to firmness and smoothness of skin; as well as post inflammatory hyper-pigmentation. Microneedling combined with PRP proved to be good in treating boxcar and rolling scars but had limited efficacy in dealing with ice pick scars.

  12. Platlet Rich Plasma (PRP) Improves Fat Grafting Outcomes.

    Science.gov (United States)

    Modarressi, Ali

    2013-01-01

    Autologous fat transfer offers many qualities of a ideal soft tissue filler. Main advantages of fat grafting ensue from the fact that the lipoaspirate tissue is an abundant source of regenerative pluripotential cells. However, the reported rates of fat cell survival vary greatly in the medical literature (10-90%). Different techniques of harvesting, processing, and reinjecting the fat cells are so claimed to be responsible for these differences, without any agreement concerning the best way to process. To address this important disadvantage, we propose the addition of autologous platelet rich plasma (PRP) which is known as a natural reservoir of growth factors stimulating tissue repair and regeneration. This approach is completely autologous and immediately employed without any type of preconditioning. Platelets rich plasma (PRP) preparation included bleeding of 8 ml of blood from patient's peripheral vein in Regen Lab© tubes containing sodium citrate anticoagulant. The whole blood was centrifugated at 1500 g during 3 min. As Regen-tubes contained a special gel separator, 99 % of red blood cells were discarded from the plasma at the bottom of the gel, and >90% of platelets were harvested in 4 ml of plasma on the top of the gel, called the platelet-rich plasma (PRP). The purified fat prepared by Coleman technique was mixed with different amount of PRP for in vitro, in vivo (mice) and clinical experiments: >50% of PRP for skin rejuvenation, superficial scars correction, infraorbital region, ..., and for 20% of PRP with 80% of purified fat for deep filler indication (nasolabial folds, lips, or soft tissue defect). In vitro studies demonstrated that PRP increased fat cells survival rate and stem cells differentiation. Animal models showed that fat graft survival rate was significantly increased by addition of PRP. Several clinical cases confirmed the improvement of wound healing and fat grafting survival in facial reconstruction and aesthetic cases by association of

  13. Is PRP useful in alveolar cleft reconstruction? Platelet-rich plasma in secondary alveoloplasty.

    Science.gov (United States)

    Luaces-Rey, Ramon; Arenaz-Búa, Jorge; Lopez-Cedrún-Cembranos, José-Luis; Herrero-Patiño, Susana; Sironvalle-Soliva, Sheyla; Iglesias-Candal, Emma; Pombo-Castro, María

    2010-07-01

    Cleft lip and palate is a congenital facial malformation with an established treatment protocol. Mixed dentition period is the best moment for correct maxillary bone defect with an alveoloplasty. The aim of this surgical procedure is to facilitate dental eruption, re-establish maxillary arch, close any oro-nasal communication, give support to nasal ala, and in some cases allow dental rehabilitation with osteointegrated implants. Twenty cleft patients who underwent secondary alveoloplasty were included. In 10 of them autogenous bone graft were used and in other 10 autogenous bone and platelet-rich plasma (PRP) obtained from autogenous blood. Bone formation was compared by digital orthopantomography made on immediate post-operatory and 3 and 6 months after the surgery. No significant differences were found between both therapeutic groups on bone regeneration. We do not find justified the use of PRP for alveoloplasty in cleft patients' treatment protocol.

  14. Effect of intralesional platelet-rich plasma (PRP) treatment on clinical and ultrasonographic parameters in equine naturally occurring superficial digital flexor tendinopathies - a randomized prospective controlled clinical trial.

    Science.gov (United States)

    Geburek, Florian; Gaus, Moritz; van Schie, Hans T M; Rohn, Karl; Stadler, Peter M

    2016-09-07

    Regenerative and anti-inflammatory effects on tendinopathies have been attributed to blood-derived biologicals. To date the evidence for the efficacy of autologous platelet-rich plasma (PRP) treatment of naturally occurring equine tendinopathies is limited. The purpose of this placebo-controlled clinical trial was to describe the effect of a single treatment of equine superficial digital flexor tendon (SDFT) disease with PRP on clinical and ultrasonographic parameters. Twenty horses with naturally occurring tendinopathies of forelimb SDFTs were randomly assigned to the PRP-treated group (n = 10) or control group (n = 10) after clinical and ultrasonographic examination. The SDFTs received an intralesional treatment with autologous PRP or were injected with saline, respectively (day 0). All horses participated in a standardized exercise programme and were re-examined clinically, with B-mode ultrasonography (5 times at regular intervals) and ultrasound tissue characterization (week 12 and 24 after treatment) until week 24. Long-term performance was estimated via telephone inquiry. Compared to day 0, lameness decreased significantly by week 8 after treatment with PRP and by week 12 in the control group. Ultrasonographically there was no difference in the summarized cross sectional area between the groups at any time point. Ultrasound tissue characterization showed that echo types representing disorganized matrix decreased significantly throughout the observation period in the PRP-treated group. Echo type II, representing discontinuous fascicles, not yet aligned into lines of stress was significantly higher 24 weeks after PRP treatment. Eighty percent of the PRP treated horses reached their previous or a higher level of performance after 12 months compared to 50 % in the CG. After 24 months these proportions were 60 % and 50 %, respectively. A single intralesional treatment with PRP up to 8 weeks after onset of clinical signs of tendinopathy contributes

  15. [Platelet rich plasma (PRP): potentialities and techniques of extraction].

    Science.gov (United States)

    Pacifici, L; Casella, F; Maggiore, C

    2002-01-01

    This paper describes the various techniques of platelet-rich plasma (PRP) extraction codified in recent years and their use potential is evaluated. PRP is one of the techniques with which at the moment it is attempted to modulate and facilitate the cure of a wound. The use of PRP is based on the theoretical premise that by concentrating platelets the effects of the growth factors (PDGF, TGF-beta, IGF-I and -II) so released will be increased. Marx's original technique is described above all. This prescribes the sampling of a unit of blood (450-500 ml) and the use of a cell separator. We then analysed the technique of Marx and Hannon in which the quantity of blood sampled is reduced to 150 ml, and the two simplified techniques of the Sacchi and Bellanda group. Finally, a new PRP extraction technique is described. We conclude that platelet gel allows access to autologous growth factors which by definition are neither toxic nor immunogenic and are capable of accelerating the normal processes of bone regeneration. PRP can thus be considered a useful instrument for increasing the quality and final quantity of regenerated bone in oral and maxillo-facial surgery operations.

  16. CONTAMINATED PROBLEMATIC SKIN WOUNDS IN DIABETIC PATIENTS TREATED WITH AUTOLOGOUS PLATELET-RICH PLASMA (PRP: A case series study

    Directory of Open Access Journals (Sweden)

    Tsvetan Sokolov

    2016-03-01

    Full Text Available OBJECTIVE: To study the effect of platelet-rich plasma (PRP on contaminated problematic skin ulcers in patients with diabetes. MATERIAL AND METHODS: A total of 6 patients had been treated within the period from 2012 to 2014; they had various types of problematic wounds and diabetes type 2. Patients’ distribution by sex was as follows: 1 man and 5 women; mean age- 68 years. Ulcer types: acute (2 patients, hard-to-heal (2 patients and chronic (2 patients ulcers. The mean size of the skin and soft tissue defect was 9,5 cm2. Pathogenic microflora was isolated in 4 patients - S. aureus in three and Е. Coli in one. Based on a scheme developed by us, all cases were treated by administering platelet-rich plasma, derived by PRGF Endoret system. Follow-up period was within 4 – 6 months (4,5 on average. We used platelet rich plasma derived by PRGF Endoret system, applied on the wound bed on a weekly basis. RESULTS: Application of PRP allowed successful closure of all wounds. There were no complications associated with treatment of PRP. Epithelialization of the wound took 15 weeks on average for all patients. One patient presented with hyperkeratosis. Initial score of followed wounds, based on the scales are as follows: Total wound score – 10 p. Total anatomic score – 8 p. Total score – 15 p. at the initial stage. At the end of the treatment period scores were as follows - 0 p., which means excellent results CONCLUSION: We believe that the application of PRP may become optimal therapy in the treatment of contaminated problematic wounds in diabetic patients. PRP not only stimulates wound healing, but also has antimicrobial properties, which may contribute to the prevention of infections.

  17. CLINICAL RESULTS FROM THE TREATMENT OF CHRONIC SKIN WOUNDS WITH PLATELET RICH PLASMA (PRP

    Directory of Open Access Journals (Sweden)

    Pencho Kossev

    2015-12-01

    Full Text Available PURPOSE: To show platelet rich plasma (PRP application of chronic skin wounds and to evaluate the results from the treatment. MATERIAL AND METHODS: A total of 14 patients with problematic skin wounds had been treated at the clinic for a period of five years (from May 2009 to December 2014 with the following patient sex ratio: male patients - 5 and female patients - 9. Average age - 48,5 (30-76. Patients with Type 2 Diabetes - 4, with decubitus ulcers - 6, traumatic - 8, with infection - 5. Based on a scheme developed by us, all cases were treated by administering platelet-rich plasma, derived by PRGF Endoret system. Follow-up period was within 4 - 6 months (4,5 on average. RESULTS: The results have been evaluated based on the following functional scoring systems - Total wound score, Total anatomic score and Total score (20. The baseline values at the very beginning of the follow-up period were as follows: Total wound score - 12 p.; Total anatomic score - 10 p., Total score - 17 p. By the end of the treatment period the score was 0 p., which means excellent results, i.e. complete healing of the wounds. CONCLUSION: We believe that the application of PRP may become optimal therapy in the treatment of difficult to heal wounds around joints, bone, subject tendons, plantar surface of the foot, etc., as it opens new perspectives in the field of human tissue regeneration.

  18. Intra-articular laser treatment plus Platelet Rich Plasma (PRP) significantly reduces pain in many patients who had failed prior PRP treatment

    Science.gov (United States)

    Prodromos, Chadwick C.; Finkle, Susan; Dawes, Alexander; Dizon, Angelo

    2018-02-01

    INTRODUCTION: In our practice Platelet Rich Plasma (PRP) injections effectively reduce pain in most but not all arthritic patients. However, for patients who fail PRP treatment, no good alternative currently exists except total joint replacement surgery. Low level laser therapy (LLLT) on the surface of the skin has not been helpful for arthritis patients in our experience. However, we hypothesized that intra-articular laser treatment would be an effective augmentation to PRP injection and would increase its efficacy in patients who had failed prior PRP injection alone. METHODS: We offered Intra-articular Low Level Laser Therapy (IAL) treatment in conjunction with repeat PRP injection to patients who had received no benefit from PRP injection alone at our center. They were the treatment group. They were not charged for PRP or IAL. They also served as a historical control group since they had all had failed PRP treatment alone. 28 patients (30 joints) accepted treatment after informed consent. 22 knees, 4 hips, 2 shoulder glenohumeral joints and 1 first carpo-metacarpal (1st CMC) joint were treated RESULTS: All patients were followed up at 1 month and no adverse events were seen from the treatment. At 6 months post treatment 46% of patients had good outcomes, and at 1 year 17% still showed improvement after treatment. 11 patients failed treatment and went on to joint replacement. DISCUSSION: A single treatment of IAL with PRP salvaged 46% of patients who had failed PRP treatment alone, allowing avoidance of surgery and good pain control.

  19. Purification and Fibrillation of Full-Length Recombinant PrP

    OpenAIRE

    Makarava, Natallia; Baskakov, Ilia V.

    2012-01-01

    Misfolding and aggregation of prion protein (PrP) is related to several neurodegenerative diseases in humans such as Creutzfeldt–Jacob disease, fatal familial insomnia, and Gerstmann–Straussler–Sheinker disease. Certain applications in prion area require recombinant PrP of high purity and quality. Here, we report an experimental procedure for expression and purification of full-length mammalian PrP. This protocol has been proved to yield PrP of extremely high purity that lac...

  20. The influence of training on the attentional blink and psychological refractory period.

    Science.gov (United States)

    Garner, K G; Tombu, M N; Dux, P E

    2014-05-01

    A growing body of research suggests that dual-task interference in sensory consolidation (e.g., the attentional blink, AB) and response selection (e.g., the psychological refractory period, PRP) stems from a common central bottleneck of information processing. With regard to response selection, it is well known that training reduces dual-task interference. We tested whether training that is known to be effective for response selection can also reduce dual-task interference in sensory consolidation. Over two experiments, performance on a PRP paradigm (Exp. 1) and on AB paradigms (differing in their stimuli and task demands, Exps. 1 and 2) was examined after participants had completed a relevant training regimen (T1 practice for both paradigms), an irrelevant training regimen (comparable sensorimotor training, not related to T1 for both tasks), a visual-search training regimen (Exp. 2 only), or after participants had been allocated to a no-training control group. Training that had shown to be effective for reducing dual-task interference in response selection was also found to be effective for reducing interference in sensory consolidation. In addition, we found some evidence that training benefits transferred to the sensory consolidation of untrained stimuli. Collectively, these findings show that training benefits can transfer across cognitive operations that draw on the central bottleneck in information processing. These findings have implications for theories of the AB and for the design of cognitive-training regimens that aim to produce transferable training benefits.

  1. PRP: The Proven Solution for Cleaning Up Oil Spills

    Science.gov (United States)

    2006-01-01

    The basic technology behind PRP is thousands of microcapsules, tiny balls of beeswax with hollow centers. Water cannot penetrate the microcapsule s cell, but oil is absorbed right into the beeswax spheres as they float on the water s surface. This way, the contaminants, chemical compounds that originally come from crude oil such as fuels, motor oils, or petroleum hydrocarbons, are caught before they settle. PRP works well as a loose powder for cleaning up contaminants in lakes and other ecologically fragile areas. The powder can be spread over a contaminated body of water or soil, and it will absorb contaminants, contain them in isolation, and dispose of them safely. In water, it is important that PRP floats and keeps the oil on the surface, because, even if oil exposure is not immediately lethal, it can cause long-term harm if allowed to settle. Bottom-dwelling fish exposed to compounds released after oil spills may develop liver disease, in addition to reproductive and growth problems. This use of PRP is especially effective for environmental cleanup in sensitive areas like coral reefs and mangroves.

  2. PrP Conformational Transitions Alter Species Preference of a PrP-specific antibody

    NARCIS (Netherlands)

    Zou, W.Q.; Langeveld, J.P.M.; Xiao, X.; Chen, S.; McGeer, P.L.; Yuan, J.; Payne, M.C.; Kang, H.E.; McGeehan, J.M.; Sy, M.S.; Greenspan, N.S.; Kaplan, D.; Wang, G.X.; Parchi, P.; Hoover, E.A.; Kneale, G.; Telling, G.; Surewicz, W.; Kong, Q.; Guo, J.

    2010-01-01

    The epitope of the 3F4 antibody most commonly used in human prion disease diagnosis is believed to consist of residues Met-Lys-His-Met (MKHM) corresponding to human PrP-(109–112). This assumption is based mainly on the observation that 3F4 reacts with human and hamster PrP but not with PrP from

  3. Contingent capture of visual-spatial attention depends on capacity-limited central mechanisms: evidence from human electrophysiology and the psychological refractory period.

    Science.gov (United States)

    Brisson, Benoit; Leblanc, Emilie; Jolicoeur, Pierre

    2009-02-01

    It has recently been demonstrated that a lateralized distractor that matches the individual's top-down control settings elicits an N2pc wave, an electrophysiological index of the focus of visual-spatial attention, indicating that contingent capture has a visual-spatial locus. Here, we investigated whether contingent capture required capacity-limited central resources by incorporating a contingent capture task as the second task of a psychological refractory period (PRP) dual-task paradigm. The N2pc was used to monitor where observers were attending while they performed concurrent central processing known to cause the PRP effect. The N2pc elicited by the lateralized distractor that matched the top-down control settings was attenuated in high concurrent central load conditions, indicating that although involuntary, the deployment of visual-spatial attention occurring during contingent capture depends on capacity-limited central resources.

  4. Identification of PrP sequences essential for the interaction between the PrP polymers and Aβ peptide in a yeast-based assay

    OpenAIRE

    Rubel, Aleksandr A; Ryzhova, Tatyana A; Antonets, Kirill S; Chernoff, Yury O; Galkin, Alexey P

    2013-01-01

    Alzheimer disease is associated with the accumulation of oligomeric amyloid β peptide (Aβ), accompanied by synaptic dysfunction and neuronal death. Polymeric form of prion protein (PrP), PrPSc, is implicated in transmissible spongiform encephalopathies (TSEs). Recently, it was shown that the monomeric cellular form of PrP (PrPC), located on the neuron surface, binds Aβ oligomers (and possibly other β-rich conformers) via the PrP23–27 and PrP90–110 segments, acting as Aβ receptor. On the other...

  5. Ubiquitin Ligase gp78 Targets Unglycosylated Prion Protein PrP for Ubiquitylation and Degradation

    OpenAIRE

    Shao, Jia; Choe, Vitnary; Cheng, Haili; Tsai, Yien Che; Weissman, Allan M.; Luo, Shiwen; Rao, Hai

    2014-01-01

    Prion protein PrP is a central player in several devastating neurodegenerative disorders, including mad cow disease and Creutzfeltd-Jacob disease. Conformational alteration of PrP into an aggregation-prone infectious form PrPSc can trigger pathogenic events. How levels of PrP are regulated is poorly understood. Human PrP is known to be degraded by the proteasome, but the specific proteolytic pathway responsible for PrP destruction remains elusive. Here, we demonstrate that the ubiquitin ligas...

  6. Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models.

    Directory of Open Access Journals (Sweden)

    Gonglin Yuan

    Full Text Available Two new PRP conjugate Algorithms are proposed in this paper based on two modified PRP conjugate gradient methods: the first algorithm is proposed for solving unconstrained optimization problems, and the second algorithm is proposed for solving nonlinear equations. The first method contains two aspects of information: function value and gradient value. The two methods both possess some good properties, as follows: 1 βk ≥ 0 2 the search direction has the trust region property without the use of any line search method 3 the search direction has sufficient descent property without the use of any line search method. Under some suitable conditions, we establish the global convergence of the two algorithms. We conduct numerical experiments to evaluate our algorithms. The numerical results indicate that the first algorithm is effective and competitive for solving unconstrained optimization problems and that the second algorithm is effective for solving large-scale nonlinear equations.

  7. Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models.

    Science.gov (United States)

    Yuan, Gonglin; Duan, Xiabin; Liu, Wenjie; Wang, Xiaoliang; Cui, Zengru; Sheng, Zhou

    2015-01-01

    Two new PRP conjugate Algorithms are proposed in this paper based on two modified PRP conjugate gradient methods: the first algorithm is proposed for solving unconstrained optimization problems, and the second algorithm is proposed for solving nonlinear equations. The first method contains two aspects of information: function value and gradient value. The two methods both possess some good properties, as follows: 1) βk ≥ 0 2) the search direction has the trust region property without the use of any line search method 3) the search direction has sufficient descent property without the use of any line search method. Under some suitable conditions, we establish the global convergence of the two algorithms. We conduct numerical experiments to evaluate our algorithms. The numerical results indicate that the first algorithm is effective and competitive for solving unconstrained optimization problems and that the second algorithm is effective for solving large-scale nonlinear equations.

  8. Study of PrP - I heterogeneous equilibrium

    International Nuclear Information System (INIS)

    Vasil'eva, I.G.; Mironov, K.E.; Tarasenko, A.D.

    1976-01-01

    Using static methods the authors have measured the equilibrium vapor pressure in the system PrP+I 2 at different temperatures and different initial iodine concentrations. The equilibrium reactions in the system have been determined. The reaction of PrP with iodine is irreversible. The content of PrI 3 and I 2 in the gas phase is negligible. The pressure in the system is determined by the partial pressure of phosphorus

  9. Impact of local anaesthetics and needle calibres used for painless PRP injections on platelet functionality.

    Science.gov (United States)

    Bausset, Olivier; Magalon, Jeremy; Giraudo, Laurent; Louis, Marie-Laure; Serratrice, Nicolas; Frere, Corrine; Magalon, Guy; Dignat-George, Françoise; Sabatier, Florence

    2014-01-01

    The platelet-rich plasma (PRP) is an autologous biotherapy commonly used for its healing properties. Once activated, platelets released a real "cocktail" of growth factor and cytokines implied in numerous regenerative processes. However the impact of medical practices associated to PRP therapeutic use on platelets functionality remains poorly known. we evaluated the in vitro effects of two commonly used local anesthetics (Xylocaine(*) and Naropin(*)) on PRP functionality. We also investigated the quantity and quality of PRP that passed through the smallest gauge needle commercialized. PRP from 9 healthy volunteers were prepared using our previously described home made purification protocol. Platelet aggregation capacity was evaluated by aggregometry assays and the growth factor release was determined by ELISA after platelet activation. We also evaluated the platelet activation status, reactivity and stability of platelets by flow cytometry using the P-selectin expression marker. the association of local anaesthetics with PRP injections resulted in a significant decrease of platelets functionality, assessed by their capacity of aggregating. Local anaesthetics did not interfere with the growth factor release. The different needle sizes and calibres tested for PRP injections did not influence the platelet functionality. the use of local anaesthetics to prevent pain during PRP injections could compromise the therapeutic potential of PRP. These results suggest using carefully local anaesthetics or limiting their use as often is possible. To minimize injection pain, we recommend using 30 G needles. These data will lead to clinical recommendations for painless and controlled PRP injections.

  10. Interaction between 14-3-3β and PrP influences the dimerization of 14-3-3 and fibrillization of PrP106-126.

    Science.gov (United States)

    Han, Jun; Song, Qin-Qin; Sun, Peng; Zhang, Jin; Wang, Xu; Song, Juan; Li, Gong-Qi; Liu, Ying-Hui; Mei, Guo-Yong; Shi, Qi; Tian, Chan; Chen, Cao; Gao, Chen; Zhao, Bo; Dong, Xiao-Ping

    2014-02-01

    Proteins of the 14-3-3 family are universal participate in multiple cellular processes. However, their exact role in the pathogenesis of prion diseases remains unclear. In this study, we proposed that human PrP was able to form molecular complex with 14-3-3β. The domains responsible for the interactions between PrP and 14-3-3β were mapped at the segments of amino acid (aa) residues 106-126 within PrP and aa 1-38 within 14-3-3β. Homology modeling revealed that the key aa residues for molecular interaction were D22 and D23 in 14-3-3β as well as K110 in PrP. Mutations in these aa residues inhibited the interaction between the two proteins in vitro. Our results also showed that recombinant PrP encouraged 14-3-3β dimer formation, whereas PrP106-126 peptide inhibited it. Recombinant 14-3-3β disaggregated the mature PrP106-126 fibrils in vitro. Moreover, the PrP-14-3-3 protein complexes were observed in the brain tissues of normal and scrapie agent 263K infected hamsters. Colocalization of PrP and 14-3-3 was seen in the cytoplasm of human neuroblastoma cell line SH-SY5Y, as well as human cervical cancer cell line HeLa transiently expressing full-length human PrP. Our current data suggest the neuroprotection of PrPC and neuron damage caused by PrPSc may be associated with their functions of 14-3-3 dimerization regulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. PLATELET-RICH PLASMA (PRP FOR THE TREATMENT OF PROBLEMATIC SKIN WOUNDS

    Directory of Open Access Journals (Sweden)

    Tsvetan Sokolov

    2016-12-01

    Full Text Available OBJECTIVE: To show platelet-rich plasma (PRP application of problematic skin wounds and to evaluate the results from the treatment. MATERIAL AND METHODS: A total of 31 patients with problematic skin wounds had been treated at the clinic for a period of five years (from May 2010 to September 2015 with the following patient sex ratio: male patients– 13 and female patients– 18. Average age– 46,5 (22-82. Patients with Type 2 Diabetes– 10, with decubitus ulcers– 2, traumatic– 29, with infection– 12, acute– 15, chronic– 16. Based on a scheme developed by us, all cases were treated by administering platelet-rich plasma, derived by PRGF Endoret system. Follow-up period was within 4 – 6 months (4,5 on average. We used platelet rich plasma derived by PRGF Endoret system, applied on the wound bed on a weekly basis. RESULTS: The results have been evaluated based on the following functional scoring systems - Total wound score, Total anatomic score and Total score (20. The baseline values at the very beginning of the follow-up period were as follows: Total wound score – 10 p.; Total anatomic score – 8 p., Total score – 15 p. By the end of the treatment period the score was 0 p., which means excellent results, i.e. complete healing of the wounds. CONCLUSION: We believe that the application of PRP may become optimal therapy in the treatment of difficult to heal wounds around joints, bone, subject tendons, plantar surface of the foot, etc., as it opens new perspectives in the field of human tissue regeneration.

  12. Matrix metalloproteinase content and activity in low-platelet, low-leukocyte and high-platelet, high-leukocyte platelet rich plasma (PRP) and the biologic response to PRP by human ligament fibroblasts.

    Science.gov (United States)

    Pifer, Matthew A; Maerz, Tristan; Baker, Kevin C; Anderson, Kyle

    2014-05-01

    concentration (P = .002) compared with controls, but no difference in MMP-3 concentration was found. At 48 hours, there was a significantly higher concentration of MMP-9 in the cell culture media of ACP-treated cells compared with GPS-treated cells (P = .003). PRP prepared as both ACP and GPS contains MMP-2, -3, and -9, which is released over a period of at least 6 days. Furthermore, a large proportion of these MMPs are in their active form, and MMP activity is dependent on platelet count within the PRP preparation. Once exposed to ligament fibroblasts, both ACP and GPS cause the fibroblasts to release MMPs, most notably 24 hours after PRP exposure, and this release is dependent on prior IL-1β stimulation. The results of this study demonstrate that PRP therapy delivers ng/mL-range concentrations of catabolic proteases, which could perpetuate inflammation and inhibit tissue healing.

  13. HGF Mediates the Anti-inflammatory Effects of PRP on Injured Tendons

    Science.gov (United States)

    Zhang, Jianying; Middleton, Kellie K.; Fu, Freddie H.; Im, Hee-Jeong; Wang, James H-C.

    2013-01-01

    Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2. PMID:23840657

  14. HGF mediates the anti-inflammatory effects of PRP on injured tendons.

    Directory of Open Access Journals (Sweden)

    Jianying Zhang

    Full Text Available Platelet-rich plasma (PRP containing hepatocyte growth factor (HGF and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2.

  15. Cytosolic PrP Can Participate in Prion-Mediated Toxicity

    Science.gov (United States)

    Thackray, Alana M.; Zhang, Chang; Arndt, Tina

    2014-01-01

    ABSTRACT Prion diseases are characterized by a conformational change in the normal host protein PrPC. While the majority of mature PrPC is tethered to the plasma membrane by a glycosylphosphatidylinositol anchor, topological variants of this protein can arise during its biosynthesis. Here we have generated Drosophila transgenic for cytosolic ovine PrP in order to investigate its toxic potential in flies in the absence or presence of exogenous ovine prions. While cytosolic ovine PrP expressed in Drosophila was predominantly detergent insoluble and showed resistance to low concentrations of proteinase K, it was not overtly detrimental to the flies. However, Drosophila transgenic for cytosolic PrP expression exposed to classical or atypical scrapie prion inocula showed a faster decrease in locomotor activity than similar flies exposed to scrapie-free material. The susceptibility to classical scrapie inocula could be assessed in Drosophila transgenic for panneuronal expression of cytosolic PrP, whereas susceptibility to atypical scrapie required ubiquitous PrP expression. Significantly, the toxic phenotype induced by ovine scrapie in cytosolic PrP transgenic Drosophila was transmissible to recipient PrP transgenic flies. These data show that while cytosolic PrP expression does not adversely affect Drosophila, this topological PrP variant can participate in the generation of transmissible scrapie-induced toxicity. These observations also show that PrP transgenic Drosophila are susceptible to classical and atypical scrapie prion strains and highlight the utility of this invertebrate host as a model of mammalian prion disease. IMPORTANCE During prion diseases, the host protein PrPC converts into an abnormal conformer, PrPSc, a process coupled to the generation of transmissible prions and neurotoxicity. While PrPC is principally a glycosylphosphatidylinositol-anchored membrane protein, the role of topological variants, such as cytosolic PrP, in prion-mediated toxicity and

  16. Glycan-deficient PrP stimulates VEGFR2 signaling via glycosaminoglycan.

    Science.gov (United States)

    Gao, Zhenxing; Zhang, Huixia; Hu, Fei; Yang, Liheng; Yang, Xiaowen; Zhu, Ying; Sy, Man-Sun; Li, Chaoyang

    2016-06-01

    Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. Compared to fully-glycosylated PrP, glycan-deficient PrP preferentially partitions to lipid raft. In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. Accordingly, CHO cells expressing glycan-deficient PrP lacking the GAG binding motif or cells treated with heparinase to remove GAG show diminished Akt signaling. Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. CHO cells bearing glycan-deficient PrP also exhibit enhanced cellular adhesion and migration. Based on these findings, we propose a model in which glycan-deficient PrP, GAG, and VEGFR2 interact, activating VEGFR2 and resulting in changes in cellular behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Purification and Fibrillation of Full-Length Recombinant PrP.

    Science.gov (United States)

    Makarava, Natallia; Savtchenko, Regina; Baskakov, Ilia V

    2017-01-01

    Misfolding and aggregation of prion protein are related to several neurodegenerative diseases in humans such as Creutzfeldt-Jakob disease, fatal familial insomnia, and Gerstmann-Straussler-Scheinker disease. A growing number of applications in the prion field including assays for detection of PrP Sc and methods for production of PrP Sc de novo require recombinant prion protein (PrP) of high purity and quality. Here, we report an experimental procedure for expression and purification of full-length mammalian prion protein. This protocol has been proved to yield PrP of extremely high purity that lacks PrP adducts, oxidative modifications, or truncation, which is typically generated as a result of spontaneous oxidation or degradation. We also describe methods for preparation of amyloid fibrils from recombinant PrP in vitro. Recombinant PrP fibrils can be used as a noninfectious synthetic surrogate of PrP Sc for development of prion diagnostics including generation of PrP Sc -specific antibody.

  18. Characterization of barley Prp1 gene and its expression during seed development and under abiotic stress.

    Science.gov (United States)

    Jiang, Qian-Tao; Liu, Tao; Ma, Jian; Wei, Yu-Ming; Lu, Zhen-Xiang; Lan, Xiu-Jin; Dai, Shou-Fen; Zheng, You-Liang

    2011-10-01

    The pre-mRNA processing (Prp1) gene encodes a spliceosomal protein. It was firstly identified in fission yeast and plays a regular role during spliceosome activation and cell cycle. Plant Prp1 genes have only been identified from rice, Sorghum and Arabidopsis thaliana. In this study, we reported the identification and isolation of a novel Prp1 gene from barley, and further explored its expressional pattern by using real-time quantitative RTPCR, promoter prediction and analysis of microarray data. The putative barley Prp1 protein has a similar primary structure features to those of other known Prp1 protein in this family. The results of amino acid comparison indicated that Prp1 protein of barley and other plant species has a highly conserved 30 termnal region while their 50 sequences greatly varied. The results of expressional analysis revealed that the expression level of barley Prp1 gene is always stable in different vegetative tissues, except it is up-regulated at the mid- and late stages of seed development or under the condition of cold stress. This kind of expressional pattern for barley Prp1 is also supported by our results of comparison of microarray data from barley, rice and Arabidopsis. For the molecular mechanism of its expressional pattern, we conclude that the expression of Prp1 gene may be up-regulated by the increase of pre-mRNAs and not be constitutive or ubiquitous.

  19. An introduction to application of Platelet Rich Plasma (PRP in skin rejuvenation

    Directory of Open Access Journals (Sweden)

    Mahnaz Banihashemi

    2014-04-01

    Full Text Available Platelet-rich plasma (PRP is an autologous concentration of human platelets contained in a small volume of plasma characterized by haemostatic and tissue repairing effects. Tissue repairing effects and being enriched by various kind of growth factors, has made them the focus of attention for different procedures. PRP has been effective in bony defects, wound healing and recently for aesthetic procedures in plastic surgery. The purpose of this review is to evaluate and summarize the applications of PRP in the dermatology literature, with particular focus on rejuvenizaton process, advances and limitations of current PRP therapies. We studied literature related to PRP therapy, these include regeneration of soft tissue, skin aging mechanisms, as well as wound healing. Some studies have shown promising results, with favorable outcomes about PRP clinical application for skin rejuvenization. This article summarizes our current understanding regarding photoaging process and the role of PRP in the skin rejuvenization process. PRP has been shown to be useful in skin rejuvenization. Further studies are needed to elucidate both basic and clinical aspects of PRP therapies. In particular, platelet preparation methods, different application methods, platelet mechanism of action in rejuvenation field, interactions with the skin components, long-term efficacy and safety are necessary to be determined.

  20. Performance related pay (PRP) to social workers in Danish Job Centres

    DEFF Research Database (Denmark)

    Flensborg Jensen, Maya; Rosdahl, Anders

    This paper discusses two issues: - Why has some Danish local employment administrations introduced performance related pay (PRP) for social workers while others have not? - Does PRP to social workers imply better efforts to bring long-term recipients of social assistance into employment?......This paper discusses two issues: - Why has some Danish local employment administrations introduced performance related pay (PRP) for social workers while others have not? - Does PRP to social workers imply better efforts to bring long-term recipients of social assistance into employment?...

  1. Prion propagation in cells expressing PrP glycosylation mutants.

    Science.gov (United States)

    Salamat, Muhammad K; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

    2011-04-01

    Infection by prions involves conversion of a host-encoded cell surface protein (PrP(C)) to a disease-related isoform (PrP(Sc)). PrP(C) carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrP(C) glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrP(Sc) and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrP(Sc), while PrP(C) with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrP(C), were able to form infectious PrP(Sc). Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection.

  2. Enhanced Osteogenic Differentiation of Mesenchymal Stem Cells on Electrospun PES/PVA/PRP Nanofibrous Scaffolds.

    Science.gov (United States)

    Kashef-Saberi, Mahshid Sadat; Roodbari, Nasim Hayati; Parivar, Kazem; Vakilian, Saeid; Hanee-Ahvaz, Hana

    2018-03-28

    Over the last few decades, great advancements have been achieved in the field of bone tissue engineering (BTE). Containing a great number of growth factors needed in the process of osteogenesis, platelet rich plasma (PRP) has gained a great deal of attention. However, due to the contradictory results achieved in different studies, its effectiveness remains a mystery. Therefore, in this study, we investigated in vitro performance of co-electrospun PRP/poly ether sulfone/poly(vinyl) alcohol (PRP/PES/PVA) composite scaffolds for the osteogenic differentiation of human adipose-derived mesenchymal stem cells. The activated PRP was mixed with PVA solution to be used alongside PES solution for the electrospinning process. Fourier transform infrared spectroscopy, scanning electron microscopy and tensile tests were performed to evaluate the scaffolds. After confirmation of sustained release of protein, osteogenic potential of the co-electrospun PRP/polymer scaffolds was evaluated by measuring relative gene expression, calcium content, and alkaline phosphatase (ALP) activity. Alizarin red and Hematoxylin and Eosin staining were performed as well. The results of ALP activity and calcium content demonstrated the effectiveness of PRP when combined with PRP-incorporated scaffold in comparison with the other tested groups. In addition, the results of tensile mechanical testing indicated that addition of PRP improves the mechanical properties. Taking these results into account, it appears PES/PVA/PRP scaffold treated with PRP 5% enhances osteogenic differentiation most. In conclusion, incorporation of PRP into electrospun PES/PVA scaffold in this study had a positive influence on osteogenic differentiation of AdMSCs, and thus it may have great potential for BTE applications.

  3. Redox induces diverse effects on recombinant human wild-type PrP and mutated PrP with inserted or deleted octarepeats.

    Science.gov (United States)

    Shi, Qi; Chen, Cao; Zhang, Bao-Yun; Zhou, Wei; Xiao, Kang; Dong, Xiao-Ping

    2018-04-01

    Normal prion protein (PrP) contains two cysteines at amino acids 179 and 214, which may form intra‑ and interpeptide disulfide bonds. To determine the possible effects of this disulfide bridge on the biochemical features of PrP, prokaryotic recombinant human wild‑type PrP (PG5), and mutated PrPs with seven extra octarepeats (PG12) or with all five octarepeats removed (PG0), were subjected to redox in vitro. Sedimentation assays revealed a large portion of aggregation in redox‑treated PG5, but not in PG0 and PG12. Circular dichroism analysis detected increased β‑sheet and decreased α‑helix in PG5 subjected to redox, increased random‑coil and decreased β‑sheet in PG0, and increased random‑coil, but limited changes to β‑sheet content, in PG12. Thioflavin T fluorescence tests indicated that fluorescent value was increased in PG5 subjected to redox. In addition, proteinase K (PK) digestions indicated that PK resistance was stronger in PG12 and PG0 compared with in PG5; redox enhanced the PK resistance of all three PrP constructs, particularly PG0 and PG12. These data indicated that formation of a disulfide bond induces marked alterations in the secondary structure and biochemical characteristics of PrP. In addition, the octarepeat region within the PrP peptide markedly influences the effects of redox on the biochemical phenotypes of PrP, thus highlighting the importance of the number of octarepeats in the biological functions of PrP.

  4. Recommendations for the Involvement of Patient Research Partners (PRP) in OMERACT Working Groups. A Report from the OMERACT 2014 Working Group on PRP.

    Science.gov (United States)

    Cheung, Peter P; de Wit, Maarten; Bingham, Clifton O; Kirwan, John R; Leong, Amye; March, Lyn M; Montie, Pam; Scholte-Voshaar, Marieke; Gossec, Laure

    2016-01-01

    Patient participation in research is increasing; however, practical guidelines to enhance this participation are lacking. Specifically within the Outcome Measures in Rheumatology (OMERACT) organization, although patients have participated in OMERACT meetings since 2002, consensus about the procedures for involving patients in working groups has not been formalized. The objective is to develop a set of recommendations regarding patient research partner (PRP) involvement in research working groups. We conducted a systematic literature review on recommendations/guidelines of PRP involvement in research; elaborated a structured consensus process involving multiple participants to develop a set of recommendations; and sought endorsement of recommendations by OMERACT. In the 18 articles included in the literature review, there was general agreement on the broad concepts for recommendations covering PRP involvement in research although they were heterogeneous in detail. Most considered PRP involvement in all phases of research with early engagement, training, and support important, but details on the content were scarce. This review informed a larger consensus-building process regarding PRP inclusion in OMERACT research. Three overarching principles and 8 recommendations were developed, discussed, and refined at OMERACT 2014. The guiding principles were endorsed during the OMERACT plenary session. These recommendations for PRP involvement in OMERACT research reinforce the importance of patient participation throughout the research process as integral members. Although the applicability of the recommendations in other research contexts should be assessed, the generalizability is expected to be high. Future research should evaluate their implementation and their effect on outcome development.

  5. Expressions of pathologic markers in PRP based chondrogenic differentiation of human adipose derived stem cells.

    Science.gov (United States)

    Pakfar, Arezou; Irani, Shiva; Hanaee-Ahvaz, Hana

    2017-02-01

    Optimization of the differentiation medium through using autologous factors such as PRP is of great consideration, but due to the complex, variable and undefined composition of PRP on one hand and lack of control over the absolute regulatory mechanisms in in vitro conditions or disrupted and different mechanisms in diseased tissue microenvironments in in vivo conditions on the other hand, it is complicated and rather unpredictable to get the desired effects of PRP making it inevitable to monitor the possible pathologic or undesired differentiation pathways and therapeutic effects of PRP. Therefore, in this study the probable potential of PRP on inducing calcification, inflammation and angiogenesis in chondrogenically-differentiated cells was investigated. The expressions of chondrogenic, inflammatory, osteogenic and angiogenic markers from TGFβ or PRP-treated cells during chondrogenic differentiation of human adipose-derived stem cells (ADSCs) was evaluated. Expressions of Collagen II (Col II), Aggrecan, Sox9 and Runx2 were quantified using q-RT PCR. Expression of Col II and X was investigated by immunocytochemistry as well. Glycosaminoglycans (GAGs) production was also determined by GAG assay. Possible angiogenic/inflammatory potential was determined by quantitatively measuring the secreted VEGF, TNFα and phosphorylated VEGFR2 via ELISA. In addition, the calcification of the construct was monitored by measuring ALP activity and calcium deposition. Our data showed that PRP positively induced chondrogenesis; meanwhile the secretion of angiogenic and inflammatory markers was decreased. VEGFR2 phosphorylation and ALP activity had a decreasing trend, but tissue mineralization was enhanced upon treating with PRP. Although reduction in inflammatory/angiogenic potential of the chondrogenically differentiated constructs highlights the superior effectiveness of PRP in comparison to TGFβ for chondrogenic differentiation, yet further improvement of the PRP

  6. Structural and functional analysis of the human spliceosomal DEAD-box helicase Prp28

    Energy Technology Data Exchange (ETDEWEB)

    Möhlmann, Sina [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany); Mathew, Rebecca [Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, 37077 Göttingen (Germany); Neumann, Piotr; Schmitt, Andreas [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany); Lührmann, Reinhard [Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, 37077 Göttingen (Germany); Ficner, Ralf, E-mail: rficner@uni-goettingen.de [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany)

    2014-06-01

    The crystal structure of the helicase domain of the human spliceosomal DEAD-box protein Prp28 was solved by SAD. The binding of ADP and ATP by Prp28 was studied biochemically and analysed with regard to the crystal structure. The DEAD-box protein Prp28 is essential for pre-mRNA splicing as it plays a key role in the formation of an active spliceosome. Prp28 participates in the release of the U1 snRNP from the 5′-splice site during association of the U5·U4/U6 tri-snRNP, which is a crucial step in the transition from a pre-catalytic spliceosome to an activated spliceosome. Here, it is demonstrated that the purified helicase domain of human Prp28 (hPrp28ΔN) binds ADP, whereas binding of ATP and ATPase activity could not be detected. ATP binding could not be observed for purified full-length hPrp28 either, but within an assembled spliceosomal complex hPrp28 gains ATP-binding activity. In order to understand the structural basis for the ATP-binding deficiency of isolated hPrp28, the crystal structure of hPrp28ΔN was determined at 2.0 Å resolution. In the crystal the helicase domain adopts a wide-open conformation, as the two RecA-like domains are extraordinarily displaced from the productive ATPase conformation. Binding of ATP is hindered by a closed conformation of the P-loop, which occupies the space required for the γ-phosphate of ATP.

  7. The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting.

    Directory of Open Access Journals (Sweden)

    Mohssen Hakimi

    Full Text Available One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC. The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group. In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG, whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting.

  8. What About the Rheological Properties of PRP/Microfat Mixtures in Fat Grafting Procedure?

    Science.gov (United States)

    Ghazouane, R; Bertrand, B; Philandrianos, C; Veran, J; Abellan, M; Francois, P; Velier, M; Orneto, C; Piccerelle, P; Magalon, J

    2017-10-01

    Fat grafting has emerged as a reference procedure in daily plastic surgery practice. Unpredictable fat resorption is the main clinical problem. For this purpose, the addition of PRP to enhance fat revascularization is now an easy and popular procedure. However, no consensus exists regarding the respective volume of fat and PRP used to obtain the ideal mixture. This study investigated the rheological properties of microfat mixed with different proportions of PRP. Results obtained were compared with commercialized hyaluronic acid fillers. Microfat and PRP preparations were performed using standardized techniques. Lipoaspirate residue and blood were obtained from six patients undergoing aesthetic facial microlipofilling. Elastic modulus G' and tan δ (proportion of elasticity versus fluidity) were obtained for the following conditions: microfat alone and microfat mixed with 10, 30 or 50% of PRP. An expected decrease in elastic modulus was observed by adding increase volumes of PRP. Two groups of products with different rheological properties were considered based on statistical differences highlighted regarding the value of G'. Mean tan δ varied from 0.20 ± 0.04 (microfat alone) to 0.28 ± 0.08 (50% microfat/50% PRP). Microfat mixed with 10% of PRP presents consistency comparable to stiffer fillers, whereas microfat mixed with 30 or 50% corresponds to softer fillers. Rheological differences were highlighted given the proportion of PRP added to the microfat. Further studies assessing the impact of increased doses of platelets in microfat/PRP mixtures on clinical outcomes should also be investigated. Our findings will help clinicians to choose a mixture that meets their specific needs for a given indication. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

  9. Semisynthetic prion protein (PrP) variants carrying glycan mimics at position 181 and 197 do not form fibrils.

    Science.gov (United States)

    Araman, Can; Thompson, Robert E; Wang, Siyao; Hackl, Stefanie; Payne, Richard J; Becker, Christian F W

    2017-09-01

    The prion protein (PrP) is an N -glycosylated protein attached to the outer leaflet of eukaryotic cell membranes via a glycosylphosphatidylinositol (GPI) anchor. Different prion strains have distinct glycosylation patterns and the extent of glycosylation of potentially pathogenic misfolded prion protein (PrP Sc ) has a major impact on several prion-related diseases (transmissible spongiform encephalopathies, TSEs). Based on these findings it is hypothesized that posttranslational modifications (PTMs) of PrP influence conversion of cellular prion protein (PrP C ) into PrP Sc and, as such, modified PrP variants are critical tools needed to investigate the impact of PTMs on the pathogenesis of TSEs. Here we report a semisynthetic approach to generate PrP variants modified with monodisperse polyethyleneglycol (PEG) units as mimics of N-glycans. Incorporating PEG at glycosylation sites 181 and 197 in PrP induced only small changes to the secondary structure when compared to unmodified, wildtype PrP. More importantly, in vitro aggregation was abrogated for all PEGylated PrP variants under conditions at which wildtype PrP aggregated. Furthermore, the addition of PEGylated PrP as low as 10 mol% to wildtype PrP completely blocked aggregation. A similar effect was observed for synthetic PEGylated PrP segments comprising amino acids 179-231 alone if these were added to wildtype PrP in aggregation assays. This behavior raises the question if large N-glycans interfere with aggregation in vivo and if PEGylated PrP peptides could serve as potential therapeutics.

  10. The differential effects of leukocyte-containing and pure platelet-rich plasma (PRP) on tendon stem/progenitor cells - implications of PRP application for the clinical treatment of tendon injuries.

    Science.gov (United States)

    Zhou, Yiqin; Zhang, Jianying; Wu, Haishan; Hogan, MaCalus V; Wang, James H-C

    2015-09-15

    Platelet-rich plasma (PRP) is widely used to treat tendon injuries in clinics. These PRP preparations often contain white blood cells or leukocytes, and the precise cellular effects of leukocyte-rich PRP (L-PRP) on tendons are not well defined. Therefore, in this study, we determined the effects of L-PRP on tendon stem/progenitor cells (TSCs), which play a key role in tendon homeostasis and repair. TSCs isolated from the patellar tendons of rabbits were treated with L-PRP or P-PRP (pure PRP without leukocytes) in vitro, followed by measuring cell proliferation, stem cell marker expression, inflammatory gene expression, and anabolic and catabolic protein expression by using immunostaining, quantitative real-time polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay, respectively. Cell proliferation was induced by both L-PRP and P-PRP in a dose-dependent manner with maximum proliferation at a 10 % PRP dose. Both PRP treatments also induced differentiation of TSCs into active tenocytes. Nevertheless, the two types of PRP largely differed in several effects exerted on TSCs. L-PRP induced predominantly catabolic and inflammatory changes in differentiated tenocytes; its treatment increased the expression of catabolic marker genes, matrix metalloproteinase-1 (MMP-1), MMP-13, interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α), and their respective protein expression and prostaglandin E2 (PGE 2) production. In contrast, P-PRP mainly induced anabolic changes; that is, P-PRP increased the gene expression of anabolic genes, alpha-smooth muscle actin (α-SMA), collagen types I and III. These findings indicate that, while both L-PRP and P-PRP appear to be "safe" in inducing TSC differentiation into active tenocytes, L-PRP may be detrimental to the healing of injured tendons because it induces catabolic and inflammatory effects on tendon cells and may prolong the effects in healing tendons. On the other hand, when P-PRP is used to

  11. Membrane paradigm

    International Nuclear Information System (INIS)

    Price, R.H.; Thorne, K.S.

    1986-01-01

    The membrane paradigm is a modified frozen star approach to modeling black holes, with particles and fields assuming a complex, static, boundary-layer type structure (membrane) near the event horizon. The membrane has no effects on the present or future evolution of particles and fields above itself. The mathematical representation is a combination of a formalism containing terms for the shear and bulk viscosity, surface pressure, momentum, temperature, entropy, etc., of the horizon and the 3+1 formalism. The latter model considers a family of three-dimensional spacelike hypersurfaces in one-dimensional time. The membrane model considers a magnetic field threading the hole and undergoing torque from the hole rotation. The field is cleaned by the horizon and distributed over the horizon so that ohmic dissipation is minimized. The membrane paradigm is invalid inside the horizon, but is useful for theoretically probing the properties of slowly evolving black holes

  12. Effects of platelet rich plasma (PRP) on human gingival fibroblast, osteoblast and periodontal ligament cell behaviour.

    Science.gov (United States)

    Kobayashi, Eizaburo; Fujioka-Kobayashi, Masako; Sculean, Anton; Chappuis, Vivianne; Buser, Daniel; Schaller, Benoit; Dőri, Ferenc; Miron, Richard J

    2017-06-02

    The use of platelet rich plasma (PRP, GLO) has been used as an adjunct to various regenerative dental procedures. The aim of the present study was to characterize the influence of PRP on human gingival fibroblasts, periodontal ligament (PDL) cells and osteoblast cell behavior in vitro. Human gingival fibroblasts, PDL cells and osteoblasts were cultured with conditioned media from PRP and investigated for cell migration, proliferation and collagen1 (COL1) immunostaining. Furthermore, gingival fibroblasts were tested for genes encoding TGF-β, PDGF and COL1a whereas PDL cells and osteoblasts were additionally tested for alkaline phosphatase (ALP) activity, alizarin red staining and mRNA levels of osteoblast differentiation markers including Runx2, COL1a2, ALP and osteocalcin (OCN). It was first found that PRP significantly increased cell migration of all cells up to 4 fold. Furthermore, PRP increased cell proliferation at 3 and 5 days of gingival fibroblasts, and at 3 days for PDL cells, whereas no effect was observed on osteoblasts. Gingival fibroblasts cultured with PRP increased TGF-β, PDGF-B and COL1 mRNA levels at 7 days and further increased over 3-fold COL1 staining at 14 days. PDL cells cultured with PRP increased Runx2 mRNA levels but significantly down-regulated OCN mRNA levels at 3 days. No differences in COL1 staining or ALP staining were observed in PDL cells. Furthermore, PRP decreased mineralization of PDL cells at 14 days post seeding as assessed by alizarin red staining. In osteoblasts, PRP increased COL1 staining at 14 days, increased COL1 and ALP at 3 days, as well as increased ALP staining at 14 days. No significant differences were observed for alizarin red staining of osteoblasts following culture with PRP. The results demonstrate that PRP promoted gingival fibroblast migration, proliferation and mRNA expression of pro-wound healing molecules. While PRP induced PDL cells and osteoblast migration and proliferation, it tended to have

  13. Winnicott's paradigm outlined

    Directory of Open Access Journals (Sweden)

    Zeljko Loparic

    Full Text Available The main objective of this paper is to present a unified view of Winnicott’s contribution to psychoanalysis. Part I (Sections 1-4 starts off by recalling that, according to some important commentators, Winnicott introduced a change in paradigms in psychoanalysis. In order to show that this change can be viewed as an overall “switch in paradigms”, in the sense given by T. S. Kuhn, this paper presents an account of the Kuhn’s view of science and offers a reconstruction of Freud’s Oedipal, Triangular or “Toddler-in-the-Mother’s-Bed” Paradigm. Part II (Sections 5-13 shows that as early as the 1920’s Winnicott encountered insurmountable anomalies in the Oedipal paradigm and, for that reason, started what can be called revolutionary research for a new framework of psychoanalysis. This research led Winnicott, especially during the last period of his life, to produce an alternative dual or “Baby-on-the-Mother’s-Lap” Paradigm. This new paradigm is described in some detail, especially the paradigmatic dual mother-baby relation and Winnicott’s dominant theory of maturation. Final remarks are made regarding Winnicott’s heritage and the future of psychoanalysis.

  14. Comparison of the Efficacy of Homologous and Autologous Platelet-Rich Plasma (PRP) for Treating Androgenic Alopecia.

    Science.gov (United States)

    Ince, Bilsev; Yildirim, Mehmet Emin Cem; Dadaci, Mehmet; Avunduk, Mustafa Cihat; Savaci, Nedim

    2018-02-01

    Androgenetic alopecia (AGA), the most common cause of hair loss in both sexes, accounts for 95% of all cases of hair loss. Although the literature has suggested that both nonactivated (n-PRP) and activated autologous (a-PRP) PRP can be used to treat AGA, we did not find any study investigating the use of homologous PRP (h-PRP) for this purpose. Also, to the best of our knowledge, there are no studies comparing the efficacy of h-PRP, a-PRP, or n-PRP on AGA therapy. The aim of this study was to compare the increase in hair density, average number of platelets, complications, preparation, and duration of application in the treatment of AGA using a-PRP, n-PRP, and h-PRP. Between 2014 and 2015, we studied male patients who had experienced increased hair loss in the last year. Patients were divided into three groups: Group 1 received n-PRP, Group 2 received active PRP, and Group 3 received h-PRP. For Group 1, PRP was prepared by a single centrifugation prepared from the patient's own blood. For Group 2, the PRP was prepared from the patient's own blood, but a second centrifugation was applied for platelet activation with calcium chloride. For Group 3, the PRP was prepared from pooled platelets with the same blood group as the patient from the blood center. PRP was injected at 1, 2, and 6 months. The hair density (n/cm 2 ) of each patient before and after injection was calculated. Each patient was assigned a fixed evaluation point at the time of application to calculate hair density. At 2, 6, and 12 months after the first treatment, the increase in hair density was calculated as 11.2, 26.1, and 32.4%, respectively, in Group 1; 8.1, 12.5, and 20.8%, respectively, in Group 2; and 16.09, 36.41, and 41.76%, respectively, in Group 3. The increase in hair density was statistically significantly greater in Group 1 than in Group 2 and more so in Group 3 than in both groups among all controls (p PRP was greater than with autologous PRP groups. We believe that h-PRP therapy can

  15. PrP N-terminal domain triggers PrPSc-like aggregation of Dpl

    International Nuclear Information System (INIS)

    Erlich, Paul; Cesbron, Jean-Yves; Lemaire-Vieille, Catherine; Curt, Aurelie; Andrieu, Jean-Pierre; Schoehn, Guy; Jamin, Marc; Gagnon, Jean

    2008-01-01

    Transmissible spongiform encephalopathies are fatal neurodegenerative disorders thought to be transmitted by self-perpetuating conformational conversion of a neuronal membrane glycoprotein (PrP C , for 'cellular prion protein') into an abnormal state (PrP Sc , for 'scrapie prion protein'). Doppel (Dpl) is a protein that shares significant biochemical and structural homology with PrP C . In contrast to its homologue PrP C , Dpl is unable to participate in prion disease progression or to achieve an abnormal PrP Sc -like state. We have constructed a chimeric mouse protein, composed of the N-terminal domain of PrP C (residues 23-125) and the C-terminal part of Dpl (residues 58-157). This chimeric protein displays PrP-like biochemical and structural features; when incubated in presence of NaCl, the α-helical monomer forms soluble β-sheet-rich oligomers which acquire partial resistance to pepsin proteolysis in vitro, as do PrP oligomers. Moreover, the presence of aggregates akin to protofibrils is observed in soluble oligomeric species by electron microscopy

  16. PRP for Degenerative Cartilage Disease: A Systematic Review of Clinical Studies.

    Science.gov (United States)

    Laver, Lior; Marom, Niv; Dnyanesh, Lad; Mei-Dan, Omer; Espregueira-Mendes, João; Gobbi, Alberto

    2017-10-01

    To explore the utilization of platelet-rich plasma (PRP) for degenerative cartilage processes and evaluate whether there is sufficient evidence to better define its potential effects. Systematic literature reviews were conducted in PubMed/MEDLINE and Cochrane electronic databases till May 2015, using the keywords "platelet-rich plasma OR PRP OR autologous conditioned plasma OR ACP AND cartilage OR chondrocyte OR chondrogenesis OR osteoarthritis (OA) OR arthritis." The final result yielded 29 articles. Twenty-six studies examined PRP administration for knee OA and 3 involved PRP administration for hip OA. The results included 9 prospective randomized controlled trials (RCTs) (8 knee and 1 hip), 4 prospective comparative studies, 14 case series, and 2 retrospective comparative studies. Hyaluronic acid (HA) was used as a control in 11 studies (7 RCTs, 2 prospective comparative studies, and 2 retrospective cohort). Overall, all RCTs reported on improved symptoms compared to baseline scores. Only 2 RCTs-one for knee and one for hip-did not report significant superiority of PRP compared to the control group (HA). Nine out of 11 HA controlled studies showed significant better results in the PRP groups. A trend toward better results for PRP injections in patients with early knee OA and young age was observed; however, lack of uniformity was evident in terms of indications, inclusion criteria, and pathology definitions in the different studies. Current clinical evidence supports the benefit in PRP treatment for knee and hip OA, proven to temporarily relieve pain and improve function of the involved joint with superior results compared with several alternative treatments. Further research to establish the optimal preparation protocol and characteristics of PRP injections for OA is needed.

  17. Kartogenin with PRP promotes the formation of fibrocartilage zone in the tendon-bone interface.

    Science.gov (United States)

    Zhou, Yiqin; Zhang, Jianying; Yang, Jinsong; Narava, Manoj; Zhao, Guangyi; Yuan, Ting; Wu, Haishan; Zheng, Nigel; Hogan, MaCalus V; Wang, James H-C

    2017-12-01

    Treatment of tendon-bone junction injuries is a challenge because tendon-bone interface often heals poorly and the fibrocartilage zone, which reduces stress concentration, at the interface is not formed. In this study, we used a compound called kartogenin (KGN) with platelet-rich plasma (PRP) to induce the formation of fibrocartilage zone in a rat tendon graft-bone tunnel model. The experimental rats received KGN-PRP or PRP injections in the tendon graft-bone tunnel interface. The control group received saline. After 4, 8 and 12 weeks, Safranin O staining of the tendon graft-bone tunnels revealed abundant proteoglycans in the KGN-PRP group indicating the formation of cartilage-like transition zone. Immunohistochemical and immuno-fluorescence staining revealed collagen types I (Col-I) and II (Col-II) in the newly formed fibrocartilage zone. Both fibrocartilage zone formation and maturation were healing time dependent. In contrast, the PRP and saline control groups had no cartilage-like tissues and minimal Col-I and Col-II staining. Some gaps were also present in the saline control group. Finally, pull-out strength in the KGN-PRP-treated group at 8 weeks was 1.4-fold higher than the PRP-treated group and 1.6-fold higher than the saline control group. These findings indicate that KGN, with PRP as a carrier, promotes the formation of fibrocartilage zone between the tendon graft and bone interface. Thus, KGN-PRP may be used as a convenient cell-free therapy in clinics to promote fibrocartilage zone formation in rotator calf repair and anterior cruciate ligament reconstruction, thereby enhancing the mechanical strength of the tendon-bone interface and hence the clinical outcome of these procedures. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  18. CD36 participates in PrP(106-126-induced activation of microglia.

    Directory of Open Access Journals (Sweden)

    Mohammed Kouadir

    Full Text Available Microglial activation is a characteristic feature of the pathogenesis of prion diseases. The molecular mechanisms that underlie prion-induced microglial activation are not very well understood. In the present study, we investigated the role of the class B scavenger receptor CD36 in microglial activation induced by neurotoxic prion protein (PrP fragment 106-126 (PrP(106-126. We first examined the time course of CD36 mRNA expression upon exposure to PrP(106-126 in BV2 microglia. We then analyzed different parameters of microglial activation in PrP(106-126-treated cells in the presence or not of anti-CD36 monoclonal antibody (mAb. The cells were first incubated for 1 h with CD36 monoclonal antibody to block the CD36 receptor, and were then treated with neurotoxic prion peptides PrP(106-126. The results showed that PrP(106-126 treatment led to a rapid yet transitory increase in the mRNA expression of CD36, upregulated mRNA and protein levels of proinflammatory cytokines (IL-1β, IL-6 and TNF-α, increased iNOS expression and nitric oxide (NO production, stimulated the activation of NF-κB and caspase-1, and elevated Fyn activity. The blockade of CD36 had no effect on PrP(106-126-stimulated NF-κB activation and TNF-α protein release, abrogated the PrP(106-126-induced iNOS stimulation, downregulated IL-1β and IL-6 expression at both mRNA and protein levels as well as TNF-α mRNA expression, decreased NO production and Fyn phosphorylation, reduced caspase-1 cleavage induced by moderate PrP(106-126-treatment, but had no effect on caspase-1 activation after treatment with a high concentration of PrP(106-126. Together, these results suggest that CD36 is involved in PrP(106-126-induced microglial activation and that the participation of CD36 in the interaction between PrP(106-126 and microglia may be mediated by Src tyrosine kinases. Our findings provide new insights into the mechanisms underlying the activation of microglia by neurotoxic prion peptides

  19. Singlet ground-state fluctuations in praseodymium observed by muon spin relaxation in PrP and PrP0.9

    International Nuclear Information System (INIS)

    Noakes, D R; Waeppling, R; Kalvius, G M; Jr, M F White; Stronach, C E

    2005-01-01

    Muon spin relaxation (μSR) in the singlet ground-state compounds PrP and PrP 0.9 reveals the unusual situation of a Lorentzian local field distribution with fast-fluctuation-limit strong-collision dynamics, a case that does not show motional narrowing. Contrary to publications by others, where PrP 0.9 was asserted to have vacancy-induced spin-glass freezing, no spin-glass freezing is seen in PrP 0.9 or PrP down to ≤100mK. This was confirmed by magnetization measurements on these same samples. In both compounds, the muon spin relaxation rate does increase as temperature decreases, demonstrating increasing strength of the paramagnetic response. A Monte Carlo model of fluctuations of Pr ions out of their crystalline-electric-field singlet ground states into their magnetic excited states (and back down again) produces the strong-collision-dynamic Lorentzian relaxation functions observed at each individual temperature but not the observed temperature dependence. This model contains no exchange interaction, and so predicts decreasing paramagnetic response as the temperature decreases, contrary to the temperature dependence observed. Comparison of the simulations to the data suggests that the exchange interaction is causing the system to approach magnetic freezing (by mode softening), but fails to complete the process

  20. A call for a standard classification system for future biologic research: the rationale for new PRP nomenclature.

    Science.gov (United States)

    Mautner, Kenneth; Malanga, Gerard A; Smith, Jay; Shiple, Brian; Ibrahim, Victor; Sampson, Steven; Bowen, Jay E

    2015-04-01

    Autologous cell therapies including platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are increasingly popular options for soft tissue and joint-related diseases. Despite increased clinical application, conflicting research has been published regarding the efficacy of PRP, and few clinical publications pertaining to BMC are available. Preparations of PRP (and BMC) can vary in many areas, including platelet concentration, number of white blood cells, presence or absence of red blood cells, and activation status of the preparation. The potential effect of PRP characteristics on PRP efficacy is often not well understood by the treating clinician, and PRP characteristics, as well as the volume of PRP delivered, are unfortunately not included in the methods of many published research articles. It is essential to establish a standard reporting system for PRP that facilitates communication and the interpretation and synthesis of scientific investigations. Herein, the authors propose a new PRP classification system reflecting important PRP characteristics based on contemporary literature and recommend adoption of minimal standards for PRP reporting in scientific investigations. Widespread adoption of these recommendations will facilitate interpretation and comparison of clinical studies and promote scientifically based progress in the field of regenerative medicine. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  1. Comparison of hyaluronic acid and PRP intra-articular injection with combined intra-articular and intraosseous PRP injections to treat patients with knee osteoarthritis.

    Science.gov (United States)

    Su, Ke; Bai, Yuming; Wang, Jun; Zhang, Haisen; Liu, Hao; Ma, Shiyun

    2018-05-01

    The aim of this study was to evaluate the benefit provided by intraosseous infiltration combined with intra-articular injection of platelet-rich plasma to treat mild and moderate stages of knee joint degeneration (Kellgren-Lawrence score II-III) compared with other treatments, specifically intra-articular injection of PRP and of HA. Eighty-six patients with grade II to grade III knee OA according to the Kellgren-Lawrence classification were randomly assigned to intra-articular combined with intraosseous injection of PRP (group A), intra-articular PRP (group B), or intra-articular HA (group C). Patients in group A received intra-articular combined with intraosseous injection of PRP (administered twice, 2 weeks apart). Patients in group B received intra-articular injection of PRP every 14 days. Patients in group C received a series of five intra-articular injections of HA every 7 days. All patients were evaluated using the Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities (WOMAC) score before the treatment and at 1, 3, 6, 12, and 18 months after treatment. There were significant improvements at the end of the 1st month. Notably, group A patients had significantly superior VAS and WOMAC scores than were observed in groups B and C. The VAS scores were similar in groups B and group C after the 6th month. Regarding the WOMAC scores, groups B and C differed at the 1st, 3rd, 6th, and 12th months; however, no significant difference was observed at the 18th month. The combination of intraosseous with intra-articular injections of PRP resulted in a significantly superior clinical outcome, with sustained lower VAS and WOMAC scores and improvement in quality of life within 18 months.

  2. Experimental conditions and monitoring items of the prototype repository project (PRP). Research document

    International Nuclear Information System (INIS)

    Sugita, Yutaka; Ito, Akira; Kawakami, Susumu

    2003-03-01

    Various experiments are ongoing in the underground research facility 'the Hard Rock Laboratory (HRL)' of SKB in Sweden for the geological disposal of the high-level radioactive waste. International joint project Prototype Repository Project (PRP) is one of the experiments in the HRL which has some engineered barrier systems and to study the coupled behavior happening in and around the engineered barrier system. JNC has joined this international joint project PRP to obtain the information of the coupled behavior on such systematic engineered barrier system and to apply the JNC's coupled THMC analytical code to the prediction and back analysis of the PRP. The analytical code will be verified through these analyses in this project. JNC can apply the verified analytical code to assess the coupled behavior in Japan. This report summarizes the experimental conditions and monitoring items of the PRP. (author)

  3. Role of Ultrasound Guided Platelet-Rich Plasma (PRP Injection in Treatment of Lateral Epicondylitis

    Directory of Open Access Journals (Sweden)

    Enass M. Khattab

    2017-06-01

    Conclusion: We concluded that US-guided platelet-rich plasma (PRP injection for treatment of lateral epicondylitis was a safe, minimally invasive and effective procedure in improving the sonographic and pathological changes of common extensor tendon (CET.

  4. PrP aggregation can be seeded by pre-formed recombinant PrP amyloid fibrils without the replication of infectious prions.

    Science.gov (United States)

    Barron, Rona M; King, Declan; Jeffrey, Martin; McGovern, Gillian; Agarwal, Sonya; Gill, Andrew C; Piccardo, Pedro

    2016-10-01

    Mammalian prions are unusual infectious agents, as they are thought to consist solely of aggregates of misfolded prion protein (PrP). Generation of synthetic prions, composed of recombinant PrP (recPrP) refolded into fibrils, has been utilised to address whether PrP aggregates are, indeed, infectious prions. In several reports, neurological disease similar to transmissible spongiform encephalopathy (TSE) has been described following inoculation and passage of various forms of fibrils in transgenic mice and hamsters. However, in studies described here, we show that inoculation of recPrP fibrils does not cause TSE disease, but, instead, seeds the formation of PrP amyloid plaques in PrP-P101L knock-in transgenic mice (101LL). Importantly, both WT-recPrP fibrils and 101L-recPrP fibrils can seed plaque formation, indicating that the fibrillar conformation, and not the primary sequence of PrP in the inoculum, is important in initiating seeding. No replication of infectious prions or TSE disease was observed following both primary inoculation and subsequent subpassage. These data, therefore, argue against recPrP fibrils being infectious prions and, instead, indicate that these pre-formed seeds are acting to accelerate the formation of PrP amyloid plaques in 101LL Tg mice. In addition, these data reproduce a phenotype which was previously observed in 101LL mice following inoculation with brain extract containing in vivo-generated PrP amyloid fibrils, which has not been shown for other synthetic prion models. These data are reminiscent of the "prion-like" spread of aggregated forms of the beta-amyloid peptide (Aβ), α-synuclein and tau observed following inoculation of transgenic mice with pre-formed seeds of each misfolded protein. Hence, even when the protein is PrP, misfolding and aggregation do not reproduce the full clinicopathological phenotype of disease. The initiation and spread of protein aggregation in transgenic mouse lines following inoculation with pre

  5. Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study.

    Science.gov (United States)

    Tuakli-Wosornu, Yetsa A; Terry, Alon; Boachie-Adjei, Kwadwo; Harrison, Julian R; Gribbin, Caitlin K; LaSalle, Elizabeth E; Nguyen, Joseph T; Solomon, Jennifer L; Lutz, Gregory E

    2016-01-01

    To determine whether single injections of autologous platelet-rich plasma (PRP) into symptomatic degenerative intervertebral disks will improve participant-reported pain and function. Prospective, double-blind, randomized controlled study. Outpatient physiatric spine practice. Adults with chronic (≥6 months), moderate-to-severe lumbar diskogenic pain that was unresponsive to conservative treatment. Participants were randomized to receive intradiskal PRP or contrast agent after provocative diskography. Data on pain, physical function, and participant satisfaction were collected at 1 week, 4 weeks, 8 weeks, 6 months, and 1 year. Participants in the control group who did not improve at 8 weeks were offered the option to receive PRP and subsequently followed. Functional Rating Index (FRI), Numeric Rating Scale (NRS) for pain, the pain and physical function domains of the 36-item Short Form Health Survey, and the modified North American Spine Society (NASS) Outcome Questionnaire were used. Forty-seven participants (29 in the treatment group, 18 in the control group) were analyzed by an independent observer with a 92% follow-up rate. Over 8 weeks of follow-up, there were statistically significant improvements in participants who received intradiskal PRP with regards to pain (NRS Best Pain) (P = .02), function (FRI) (P = .03), and patient satisfaction (NASS Outcome Questionnaire) (P = .01) compared with controls. No adverse events of disk space infection, neurologic injury, or progressive herniation were reported following the injection of PRP. Participants who received intradiskal PRP showed significant improvements in FRI, NRS Best Pain, and NASS patient satisfaction scores over 8 weeks compared with controls. Those who received PRP maintained significant improvements in FRI scores through at least 1 year of follow-up. Although these results are promising, further studies are needed to define the subset of participants most likely to respond to biologic intradiskal

  6. DEPA classification: a proposal for standardising PRP use and a retrospective application of available devices.

    Science.gov (United States)

    Magalon, J; Chateau, A L; Bertrand, B; Louis, M L; Silvestre, A; Giraudo, L; Veran, J; Sabatier, F

    2016-01-01

    Significant biological differences in platelet-rich plasma (PRP) preparations have been highlighted and could explain the large variability in the clinical benefit of PRP reported in the literature. The scientific community now recommends the use of classification for PRP injection; however, these classifications are focused on platelet and leucocyte concentrations. This presents the disadvantages of (1) not taking into account the final volume of the preparation; (2) omitting the presence of red blood cells in PRP and (3) not assessing the efficiency of production. On the basis of standards classically used in the Cell Therapy field, we propose the DEPA (Dose of injected platelets, Efficiency of production, Purity of the PRP, Activation of the PRP) classification to extend the characterisation of the injected PRP preparation. We retrospectively applied this classification on 20 PRP preparations for which biological characteristics were available in the literature. Dose of injected platelets varies from 0.21 to 5.43 billion, corresponding to a 25-fold increase. Only a Magellan device was able to obtain an A score for this parameter. Assessments of the efficiency of production reveal that no device is able to recover more than 90% of platelets from the blood. Purity of the preparation reveals that a majority of the preparations are contaminated by red blood cells as only three devices reach an A score for this parameter, corresponding to a percentage of platelets compared with red blood cells and leucocytes over 90%. These findings should provide significant help to clinicians in selecting a system that meets their specific needs for a given indication.

  7. Platelet-rich plasma (PRP) treatment of sports-related severe acute hamstring injuries.

    Science.gov (United States)

    Guillodo, Yannick; Madouas, Gwénaelle; Simon, Thomas; Le Dauphin, Hermine; Saraux, Alain

    2015-01-01

    hamstring injury is the most common musculoskeletal disorder and one of the main causes of missed sporting events. Shortening the time to return to play (TTRTP) is a priority for athletes and sports medicine practitioners. platelet-rich plasma (PRP) injection at the site of severe acute hamstring injury increases the healing rate and shortens the TTRTP. Cohort study. all patients with ultrasonography and MRI evidence of severe acute hamstring injury between January 2012 and March 2014 were offered PRP treatment. Those who accepted received a single intramuscular PRP injection within 8 days post-injury; the other patients served as controls. The same standardized rehabilitation program was used in both groups. A physical examination and ultrasonography were performed 10 and 30 days post-injury, then a phone interview 120 days post-injury, to determine the TTRTP at the pre-injury level. of 34 patients, 15 received PRP and 19 did not. Mean TTRTP at the pre-injury level was 50.9±10.7 days in the PRP group and 52.8±15.7 days in the control group. The difference was not statistically significant. a single intramuscular PRP injection did not shorten the TTRTP in sports people with severe acute hamstring injuries.

  8. Effectiveness of PRP Injection in Reducing Recovery Time of Acute Hamstring Injury: A Critically Appraised Topic.

    Science.gov (United States)

    Manduca, Mary Lynn; Straub, Stephen J

    2017-07-17

    Clinical Scenario Hamstring strains are common athletic injuries, with a high recurrence rate (34%). 2 Recently, platelet-rich-plasma (PRP) injections have gained popularity as a potential treatment option to accelerate healing of hamstring injury. 3 Focused Clinical Question Does the combination of PRP injection and rehabilitation decrease recovery time of acute hamstring injury as compared to rehabilitation alone in collegiate athletes? Summary of Key Findings A literature search resulted in three randomized controlled trials (RCT). One study showed benefits in various outcome measures with PRP, compared to rehabilitation alone, while two showed no benefits. One study reported improved pain, ultrasonography regenerative indications, and recovery time with PRP injection following acute hamstring injury 1 , however, larger studies have shown no benefits. 7-9 The literature demonstrates conflicting evidence regarding benefits of PRP injections in hamstring injuries. Clinical Bottom Line At this time, PRP injections cannot be recommended as having value for hamstring injuries, compared to rehabilitation alone. Strength of Recommendation Due to inconsistent or limited quality patient-oriented evidence in existing literature, the strength of this recommendation is grade B, based on the Strength of Recommendation Taxonomy (SORT). 7 .

  9. Cytosolically expressed PrP GPI-signal peptide interacts with mitochondria.

    Science.gov (United States)

    Guizzunti, Gianni; Zurzolo, Chiara

    2015-01-01

    We previously reported that PrP GPI-anchor signal peptide (GPI-SP) is specifically degraded by the proteasome. Additionally, we showed that the point mutation P238S, responsible for a genetic form of prion diseases, while not affecting the GPI-anchoring process, results in the accumulation of PrP GPI-SP, suggesting the possibility that PrP GPI-anchor signal peptide could play a role in neurodegenerative prion diseases. We now show that PrP GPI-SP, when expressed as a cytosolic peptide, is able to localize to the mitochondria and to induce mitochondrial fragmentation and vacuolarization, followed by loss in mitochondrial membrane potential, ultimately resulting in apoptosis. Our results identify the GPI-SP of PrP as a novel candidate responsible for the impairment in mitochondrial function involved in the synaptic pathology observed in prion diseases, establishing a link between PrP GPI-SP accumulation and neuronal death.

  10. Polymorphisms at Amino Acid Residues 141 and 154 Influence Conformational Variation in Ovine PrP

    Science.gov (United States)

    Yang, Sujeong; Thackray, Alana M.; Hopkins, Lee; Monie, Tom P.; Burke, David F.; Bujdoso, Raymond

    2014-01-01

    Polymorphisms in ovine PrP at amino acid residues 141 and 154 are associated with susceptibility to ovine prion disease: Leu141Arg154 with classical scrapie and Phe141Arg154 and Leu141His154 with atypical scrapie. Classical scrapie is naturally transmissible between sheep, whereas this may not be the case with atypical scrapie. Critical amino acid residues will determine the range or stability of structural changes within the ovine prion protein or its functional interaction with potential cofactors, during conversion of PrPC to PrPSc in these different forms of scrapie disease. Here we computationally identified that regions of ovine PrP, including those near amino acid residues 141 and 154, displayed more conservation than expected based on local structural environment. Molecular dynamics simulations showed these conserved regions of ovine PrP displayed genotypic differences in conformational repertoire and amino acid side-chain interactions. Significantly, Leu141Arg154 PrP adopted an extended beta sheet arrangement in the N-terminal palindromic region more frequently than the Phe141Arg154 and Leu141His154 variants. We supported these computational observations experimentally using circular dichroism spectroscopy and immunobiochemical studies on ovine recombinant PrP. Collectively, our observations show amino acid residues 141 and 154 influence secondary structure and conformational change in ovine PrP that may correlate with different forms of scrapie. PMID:25126555

  11. Mechanical and Controlled PRP Injections in Patients Affected by Androgenetic Alopecia.

    Science.gov (United States)

    Gentile, Pietro; Garcovich, Simone; Scioli, Maria Giovanna; Bielli, Alessandra; Orlandi, Augusto; Cervelli, Valerio

    2018-01-27

    23 patients (18 male and 5 female) aged 21-70 years who displayed male pattern hair loss (MPHL) in Stage 1 to Stage 5 as determined by the Norwood-Hamilton classification scale, and female pattern hair loss (FPHL) in Stage 1 to Stage 2 as determined by the Ludwig classification scale, were treated with non-activated autologous platelet-rich plasma (A-PRP). Autologous blood (55 mL) was harvested using sodium citrate as an anticoagulant. A-PRP (23 mL) was produced for all cases using a closed system according to the transfusion service protocol. Following centrifugation (260 x g for 10 min) the A-PRP was inserted in a laser light selector device, and after the centrifugation, 9 mL of A-PRP was collected. The scalp of the patients affected by androgenetic alopecia (AGA) was divided into four areas (frontal, parietal, vertex, and occipital); local anesthesia was not performed. Interfollicular A-PRP injections (0.2 mL x cm 2 ) were performed by controlled and mechanical injections scheduled at a depth of 5 mm using a medical injector gun. Treatment sessions were performed with a 30-day interval. For each patient, three treatment sessions were performed. PRP was injected in the androgen-related areas of scalp affected by hair loss. Placebo (normal saline solution) was loaded in another syringe (10 mL) and injected on the adjacent side in a similar fashion.

  12. Mouse homologue of yeast Prp19 interacts with mouse SUG1, the regulatory subunit of 26S proteasome

    International Nuclear Information System (INIS)

    Sihn, Choong-Ryoul; Cho, Si Young; Lee, Jeong Ho; Lee, Tae Ryong; Kim, Sang Hoon

    2007-01-01

    Yeast Prp19 has been shown to involve in pre-mRNA splicing and DNA repair as well as being an ubiquitin ligase. Mammalian homologue of yeast Prp19 also plays on similar functional activities in cells. In the present study, we isolated mouse SUG1 (mSUG1) as binding partner of mouse Prp19 (mPrp19) by the yeast two-hybrid system. We confirmed the interaction of mPrp9 with mSUG1 by GST pull-down assay and co-immunoprecipitation assay. The N-terminus of mPrp19 including U-box domain was associated with the C-terminus of mSUG1. Although, mSUG1 is a regulatory subunit of 26S proteasome, mPrp19 was not degraded in the proteasome-dependent pathway. Interestingly, GFP-mPrp19 fusion protein was co-localized with mSUG1 protein in cytoplasm as the formation of the speckle-like structures in the presence of a proteasome inhibitor MG132. In addition, the activity of proteasome was increased in cells transfected with mPrp19. Taken together, these results suggest that mPrp19 involves the regulation of protein turnover and may transport its substrates to 26S proteasome through mSUG1 protein

  13. PARADIGMS IN CONSUMER BEHAVIOR

    OpenAIRE

    Sabrina Oktoria Sihombing

    2011-01-01

    A paradigm influences what we see and conceive about certain facts. Paradigm can also influence what we accept as a truth. Yet, the debate over which paradigm and methodology is best suit for marketing and consumer behavior has begun since 1980s. Many researchers criticized the domination of logical empiricism paradigm and offered alternative paradigm to understand marketing and consumer behavior. This article discusses several paradigms and methodology, which are part of qualitative paradigm...

  14. PARADIGMS IN CONSUMER BEHAVIOR

    Directory of Open Access Journals (Sweden)

    Sabrina Oktoria Sihombing

    2011-05-01

    Full Text Available A paradigm influences what we see and conceive about certain facts. Paradigm can also influence what we accept as a truth. Yet, the debate over which paradigm and methodology is best suit for marketing and consumer behavior has begun since 1980s. Many researchers criticized the domination of logical empiricism paradigm and offered alternative paradigm to understand marketing and consumer behavior. This article discusses several paradigms and methodology, which are part of qualitative paradigm, and compares them with positivism paradigm. This article will also point to the importance of reconciliation between qualitative and quantitative paradigm in order to improve marketing and consumer behavior studies.

  15. Exercise and the platelet activator calcium chloride both influence the growth factor content of platelet-rich plasma (PRP): overlooked biochemical factors that could influence PRP treatment

    NARCIS (Netherlands)

    Hamilton, Bruce; Tol, Johannes L.; Knez, Wade; Chalabi, Hakim

    2015-01-01

    There is strong evidence that exercise affects platelet haemostasis factors, but this potential effect on growth factor concentrations in platelet-rich plasma (PRP) has never been studied. In addition, there is a paucity of studies focusing on the effects of activating agents used in conjunction

  16. The influence of using anticoagulants (EDTA and citrate acid 3.8% toward the quantity of Platelet Rich Plasma (PRP

    Directory of Open Access Journals (Sweden)

    Lilies Anggarwati Astuti

    2016-06-01

    Full Text Available Platelet Rich Plasma (PRP is a blood concentrate that has a thrombocytes concentration several time higher than normal concentration of thrombocytes in normal human blood. PRP is a promising alternative to surgery with a safe and natural healing. The standard protocol for PRP preparation must be determined to get the right quantity and quality of the matrix of fibrin, leukocytes, platelets and growth factors. It could not be separated from the number of PRP produced. The use of PRP in the success of periodontal treatment would not be separated from methods to obtain it. To detect the influence of using anticoagulants (EDTA and citrate acid 3.8% toward the quantity of PRP. There are 41 subjects studied by taking 21 ml of venous blood in each of the seven tubes. Centrifugation performed twice with different speed, duration, use of anticoagulants then analyzed. This quantity between the two groups differed significantly between the PRP in EDTA group is higher 322.2 ml rather than citrate acid 3.8% group, then control group is higher 329.5 ml rather than citrate acid 3.8% group, while there is no difference between EDTA and control group. There is effect of the use of anticoagulants EDTA compared with citrate acid 3.8% in the quantity of PRP, and there was no effect using citrate acid 3.8% as anticoagulants in quantity of PRP.

  17. Early Delivery of Misfolded PrP from ER to Lysosomes by Autophagy

    Science.gov (United States)

    Cortes, Constanza J.; Qin, Kefeng; Norstrom, Eric M.; Green, William N.; Bindokas, Vytautas P.; Mastrianni, James A.

    2013-01-01

    Prion diseases are linked to the accumulation of a misfolded isoform (PrPSc) of prion protein (PrP). Evidence suggests that lysosomes are degradation endpoints and sites of the accumulation of PrPSc. We questioned whether lysosomes participate in the early quality control of newly generated misfolded PrP. We found PrP carrying the disease-associated T182A mutation (Mut-PrP) was delivered to lysosomes in a Golgi-independent manner. Time-lapse live cell imaging revealed early formation and uptake of GFP-tagged Mut-PrP aggregates into LysoTracker labeled vesicles. Compared with Wt-PrP, Mut-PrP expression was associated with an elevation in several markers of the autophagy-lysosomal pathway, and it extensively colocalized with the autophagosome-specific marker, LC3B. In autophagy deficient (ATG5−/−) mouse embryonic fibroblasts, or in normal cells treated with the autophagy-inhibitor 3-MA, Mut-PrP colocalization with lysosomes was reduced to a similar extent. Additionally, 3-MA selectively impaired the degradation of insoluble Mut-PrP, resulting in an increase in protease-resistant PrP, whereas the induction of autophagy by rapamycin reduced it. These findings suggest that autophagy might function as a quality control mechanism to limit the accumulation of misfolded PrP that normally leads to the generation of PrPSc. PMID:24454378

  18. Successful treatment of radiation retinopathy with panretinal photocoagulation (PRP) in a patient of orbital MALT lymphoma

    International Nuclear Information System (INIS)

    Okamoto, Hiroyuki; Chikuda, Makoto; Kadoya, Kouji

    2012-01-01

    Report a case of satisfactory progress radiation retinopathy after radiation for mucosa-associated lymphoid tissue (MALT) lymphoma. A 26-year-old male patient, referred to our department for lacrimal sac tumor. Biopsy was done by otolaryngology and radiation therapy was performed (total irradiation of 41.4 Gy) as pathological examination revealed MALT lymphoma. Soft exudates and macula edema appeared in posterior pole of the right fundus after radiotherapy. Right vision became 0.5 because of macula edema, and panretinal photocoagulation (PRP) was performed. After PRP, macula edema withdrew and right vision improved to 1.2. It is suggested that the fundus must be monitored after radiation therapy, and early treatment, such as PRP is effective in radiation retinopathy. (author)

  19. Characterization of PhPRP1, a histidine domain arabinogalactan protein from Petunia hybrida pistils.

    Science.gov (United States)

    Twomey, Megan C; Brooks, Jenna K; Corey, Jillaine M; Singh-Cundy, Anu

    2013-10-15

    An arabinogalactan protein, PhPRP1, was purified from Petunia hybrida pistils and shown to be orthologous to TTS-1 and TTS-2 from Nicotiana tabacum and NaTTS from Nicotiana alata. Sequence comparisons among these proteins, and CaPRP1 from Capsicum annuum, reveal a conserved histidine-rich domain and two hypervariable domains. Immunoblots show that TTS-1 and PhPRP1 are also expressed in vegetative tissues of tobacco and petunia respectively. In contrast to the molecular mass heterogeneity displayed by the pistil proteins, the different isoforms found in seedlings, roots, and leaves each has a discrete size (37, 80, 160, and 200 kDa) on SDS-PAGE gels. On the basis of their chemistry, distinctive domain architecture, and the unique pattern of expression, we have named this group of proteins HD-AGPs (histidine domain-arabinogalactan proteins). Copyright © 2013 Elsevier GmbH. All rights reserved.

  20. Transmission Properties of Human PrP 102L Prions Challenge the Relevance of Mouse Models of GSS.

    Science.gov (United States)

    Asante, Emmanuel A; Grimshaw, Andrew; Smidak, Michelle; Jakubcova, Tatiana; Tomlinson, Andrew; Jeelani, Asif; Hamdan, Shyma; Powell, Caroline; Joiner, Susan; Linehan, Jacqueline M; Brandner, Sebastian; Wadsworth, Jonathan D F; Collinge, John

    2015-07-01

    Inherited prion disease (IPD) is caused by autosomal-dominant pathogenic mutations in the human prion protein (PrP) gene (PRNP). A proline to leucine substitution at PrP residue 102 (P102L) is classically associated with Gerstmann-Sträussler-Scheinker (GSS) disease but shows marked clinical and neuropathological variability within kindreds that may be caused by variable propagation of distinct prion strains generated from either PrP 102L or wild type PrP. To-date the transmission properties of prions propagated in P102L patients remain ill-defined. Multiple mouse models of GSS have focused on mutating the corresponding residue of murine PrP (P101L), however murine PrP 101L, a novel PrP primary structure, may not have the repertoire of pathogenic prion conformations necessary to accurately model the human disease. Here we describe the transmission properties of prions generated in human PrP 102L expressing transgenic mice that were generated after primary challenge with ex vivo human GSS P102L or classical CJD prions. We show that distinct strains of prions were generated in these mice dependent upon source of the inoculum (either GSS P102L or CJD brain) and have designated these GSS-102L and CJD-102L prions, respectively. GSS-102L prions have transmission properties distinct from all prion strains seen in sporadic and acquired human prion disease. Significantly, GSS-102L prions appear incapable of transmitting disease to conventional mice expressing wild type mouse PrP, which contrasts strikingly with the reported transmission properties of prions generated in GSS P102L-challenged mice expressing mouse PrP 101L. We conclude that future transgenic modeling of IPDs should focus exclusively on expression of mutant human PrP, as other approaches may generate novel experimental prion strains that are unrelated to human disease.

  1. Effect of Use of Platelet-Rich Plasma (PRP) in Skin with Intrinsic Aging Process.

    Science.gov (United States)

    Charles-de-Sá, Luiz; Gontijo-de-Amorim, Natale Ferreira; Takiya, Christina Maeda; Borojevic, Radovan; Benati, Donatella; Bernardi, Paolo; Sbarbati, Andrea; Rigotti, Gino

    2018-02-15

    In previous papers, we demonstrated that the treatment of human photoaged skin with stromal-vascular fraction-enriched fat or expanded adipose-derived stem cells showed a decrease of elastosis and the appearance of new oxytalan elastic fibers in dermis and an increase in the vascular network. The utilization of fat plus platelet-rich plasma (PRP) led to an increase in the vascular permeability and reactivity of the nervous component. The purpose of this study was to analyze the histologic and ultrastructural changes of human skin after the injection of only PRP in the retroauricular area that was not exposed to sun and did not present the photoaging process, in comparison with our previous results. This study was performed in 13 patients who were candidates for facelift and whose ages ranged between 45 and 65 years. The PRP injection was performed in the mastoidea area. Fragments of skin were removed before and 3 months after treatment and analyzed by optical and electron microscopy. After the injection of PRP, we observed an increase of reticular dermis thickness because of the deposition of elastic fibers and collagen, with a fibrotic aspect. A modified pattern of adipose tissue was also found at the dermohypodermal junction. Significative regenerative aspects were not found at histologic and ultrastructural analysis. The presence of foci of moderate inflammation and microangiopathy were observed. Treatment with PRP increased reticular dermis thickness with a fibrotic aspect. In the long term, the presence of inflammation and microangiopathy caused by PRP injection could lead to trophic alteration of the skin and the precocious aging process. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

  2. Genetic human prion disease modelled in PrP transgenic Drosophila.

    Science.gov (United States)

    Thackray, Alana M; Cardova, Alzbeta; Wolf, Hanna; Pradl, Lydia; Vorberg, Ina; Jackson, Walker S; Bujdoso, Raymond

    2017-09-20

    Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrP Sc , an abnormal isomer of the normal host protein PrP C , in the brain of affected individuals. PrP Sc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or at risk from, genetic human prion disease. Increasingly, Drosophila has been used to model human neurodegenerative disease. An important unanswered question is whether genetic prion disease with concomitant spontaneous prion formation can be modelled in Drosophila We have used pUAST/PhiC31-mediated site-directed mutagenesis to generate Drosophila transgenic for murine or hamster PrP (prion protein) that carry single-codon mutations associated with genetic human prion disease. Mouse or hamster PrP harbouring an FFI (D178N) or fCJD (E200K) mutation showed mild Proteinase K resistance when expressed in Drosophila Adult Drosophila transgenic for FFI or fCJD variants of mouse or hamster PrP displayed a spontaneous decline in locomotor ability that increased in severity as the flies aged. Significantly, this mutant PrP-mediated neurotoxic fly phenotype was transferable to recipient Drosophila that expressed the wild-type form of the transgene. Collectively, our novel data are indicative of the spontaneous formation of a PrP-dependent neurotoxic phenotype in FFI- or CJD-PrP transgenic Drosophila and show that inherited human prion disease can be modelled in this invertebrate host. © 2017 The Author(s).

  3. Recombinant PrP and Its Contribution to Research on Transmissible Spongiform Encephalopathies.

    Science.gov (United States)

    Charco, Jorge M; Eraña, Hasier; Venegas, Vanessa; García-Martínez, Sandra; López-Moreno, Rafael; González-Miranda, Ezequiel; Pérez-Castro, Miguel Ángel; Castilla, Joaquín

    2017-12-14

    The misfolding of the cellular prion protein (PrP C ) into the disease-associated isoform (PrP Sc ) and its accumulation as amyloid fibrils in the central nervous system is one of the central events in transmissible spongiform encephalopathies (TSEs). Due to the proteinaceous nature of the causal agent the molecular mechanisms of misfolding, interspecies transmission, neurotoxicity and strain phenomenon remain mostly ill-defined or unknown. Significant advances were made using in vivo and in cellula models, but the limitations of these, primarily due to their inherent complexity and the small amounts of PrP Sc that can be obtained, gave rise to the necessity of new model systems. The production of recombinant PrP using E. coli and subsequent induction of misfolding to the aberrant isoform using different techniques paved the way for the development of cell-free systems that complement the previous models. The generation of the first infectious recombinant prion proteins with identical properties of brain-derived PrP Sc increased the value of cell-free systems for research on TSEs. The versatility and ease of implementation of these models have made them invaluable for the study of the molecular mechanisms of prion formation and propagation, and have enabled improvements in diagnosis, high-throughput screening of putative anti-prion compounds and the design of novel therapeutic strategies. Here, we provide an overview of the resultant advances in the prion field due to the development of recombinant PrP and its use in cell-free systems.

  4. Distribution, recovery and concentration of platelets and leukocytes in L-PRP prepared by centrifugation.

    Science.gov (United States)

    de Melo, Bruna Alice Gomes; Martins Shimojo, Andréa Arruda; Marcelino Perez, Amanda Gomes; Duarte Lana, José Fabio Santos; Andrade Santana, Maria Helena

    2018-01-01

    Platelet-rich plasma (PRP) is an autologous product prepared from whole blood (WB) that is widely used in regenerative medicine. In clinical practice, discontinuous centrifugation is used for both hand- and machine-prepared PRP. However, separation of WB fractions via centrifugation is a complex process, and the lack of clear mechanisms limits the understanding and evaluation of PRP preparation methods This paper focuses on the distribution, recovery and concentration factor of platelets and leukocytes in L-PRP (leukocyte and platelet-rich plasma) to define a concentration pattern for these blood components due to centrifugation conditions. WB collected from three healthy donors was centrifuged for 10min at 50-800 xg in a first step and then at 400 xg in a second step. The results from the first centrifugation step showed most platelets to be distributed in the upper layer (UL) and the buffy coat (BC), with approximately 14.5±5.2% retained in the bottom layer (BL). Most leukocytes were present in the BL. The greatest platelet recoveries from L-PRP were obtained at up to 150 xg (88.5±16.9%). The cumulative concentration factors with respect to the WB from the second centrifugation step were 6 and 1.2 for platelets and leukocytes, respectively. Thus, the concentration patterns delineated three centrifugation ranges with platelet/leukocyte ratios of 205±18, 325±15 and 107±4 and lymphocyte/granulocyte ratios of 1.54±0.74, 0.90±0.08 and 0.42±0.07. These findings contribute to a scientifically based standardization of L-PRP preparations. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Use of autologous platelet rich plasma (PRP) in stopping massive hemoptysis at the Lung Center of the Philippines: a pilot study.

    Science.gov (United States)

    Sarmiento, Armand Gregorio C; Danguilan, Jose Luis J; Mariano, Zenaida M; Barzaga, Maria Teresa A

    2017-01-01

    The purpose of this study is to determine the effect of using autologous platelet rich plasma (PRP) in patients having massive hemoptysis within a period of one week. This is a prospective cohort study involving 20 consecutive patients admitted who met the criteria for massive hemoptysis from July to October 2011. After stabilizing the patient, fiberoptic bronchoscopy (FOB) was performed for localization of bleeding within 6 hours from diagnosis. A 50mL of blood was extracted from the patient whom was to be used for autologous PRP concentrate. After identifying the anatomic site of bleeding, autologous PRP concentrate was instilled on the affected bronchus and was allowed to stay for 5 minutes after instillation. Patients were then monitored from the time the bleeding stopped in the first 24 hours, 2 days and 7 days respectively. Mean age of the study population with massive hemoptysis was 47 years old (SD 17.3). Majority of cases were male 18 out of 20 (90%) and smokers 14 (70%) with a normal BMI (75%). Identification of bleeding site was more commonly seen on the right upper lobe 9 out of 20 (45%). Overall, 14 out of 20 patients (70%) were reported to have stopped bleeding immediately. Subsequent hospital days showed that 8 out of 20 patients (40%) had no hemoptysis. However, one [1] post-tuberculosis (TB) bronchiectatic patient had recurrence of massive hemoptysis, approximately 250 mL per expectorate, expired within the 7 days observation and one patient had lobectomy on the 2nd day. The rest had non-massive hemoptysis wherein their expectorations were only streaks of blood. Moreover, there was one [1] patient who had recurrence of massive hemoptysis 1 week after autologous PRP infusion and was eventually intubated. Majority of the subjects, eleven [11] were diagnosed to have post-TB bronchiectasis. The rest of the patients were worked-up prior to operation. Overall, it was observed that the use of autologous PRP was able to stop bleeding in 40% of the study

  6. Site enforcement tracking system (SETS): PRP listing by site for region 9

    International Nuclear Information System (INIS)

    1993-04-01

    When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

  7. Site enforcement tracking system (SETS): PRP listing by site for region 8

    International Nuclear Information System (INIS)

    1993-04-01

    When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

  8. Site enforcement tracking system (SETS): PRP listing by site for region 10

    International Nuclear Information System (INIS)

    1993-04-01

    When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

  9. Site enforcement tracking system (SETS): PRP listing by site for region 3

    International Nuclear Information System (INIS)

    1993-04-01

    When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

  10. Site enforcement tracking system (SETS): PRP listing by site for region 2

    International Nuclear Information System (INIS)

    1993-04-01

    When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

  11. Site enforcement tracking system (SETS): PRP listing by site for region 5

    International Nuclear Information System (INIS)

    1993-04-01

    When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

  12. Site enforcement tracking system (SETS): PRP listing by site for region 6

    International Nuclear Information System (INIS)

    1993-04-01

    When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

  13. Superfund TIO videos. Set B. Basics of administrative law, and prp search process: PRP search, information exchange and access. Part 3. Audio-Visual

    International Nuclear Information System (INIS)

    1990-01-01

    The videotape is divided into two sections. Section 1 identifies the various types of administrative hearings, including quasi-legislative, quasi-judicial, and hybrid types. Section 2 provides an overview of the PRP search process; explains how and when to issue Section 104(e) letters and administrative subpoenas; outlines the enforcement authorities available in cases of non-compliance; and describes the types of information that can be released to PRPs

  14. Can platelet-rich plasma (PRP) improve bone healing? A comparison between the theory and experimental outcomes.

    Science.gov (United States)

    Malhotra, Angad; Pelletier, Matthew H; Yu, Yan; Walsh, William R

    2013-02-01

    The increased concentration of platelets within platelet-rich plasma (PRP) provides a vehicle to deliver supra-physiologic concentrations of growth factors to an injury site, possibly accelerating or otherwise improving connective tissue regeneration. This potential benefit has led to the application of PRP in several applications; however, inconsistent results have limited widespread adoption in bone healing. This review provides a core understanding of the bone healing mechanisms, and corresponds this to the factors present in PRP. In addition, the current state of the art of PRP preparation, the key aspects that may influence its effectiveness, and treatment outcomes as they relate specifically to bone defect healing are presented. Although PRP does have a sound scientific basis, its use for bone healing appears only beneficial when used in combination with osteoconductive scaffolds; however, neither allograft nor autograft appear to be appropriate carriers. Aggressive processing techniques and very high concentrations of PRP may not improve healing outcomes. Moreover, many other variables exist in PRP preparation and use that influence its efficacy; the effect of these variables should be understood when considering PRP use. This review includes the essentials of what has been established, what is currently missing in the literature, and recommendations for future directions.

  15. A comparison between platelet-rich plasma (PRP and hyaluronate acid on the healing of cartilage defects.

    Directory of Open Access Journals (Sweden)

    Ji Liu

    Full Text Available Platelet-rich plasma (PRP has offered great promise for the treatment of cartilage degradation, and has been proved to have positive effects on the restoration of cartilage lesions. But no comparative work has been done between PRP and hyaluronate acid (HA concerning their restoring effect on cartilage defect, especially by means of animal experiments and histologic assessments. The purpose of the study was to compare the therapeutic effects of P-PRP and HA on osteoarthritis in rabbit knees. Thirty rabbits were used to establish the animal models by creating a cartilage defect of 5 mm in diameter on the condyles of the femurs, and were randomly divided into three groups: the P-PRP group, HA group and the control group. Then each group was treated with P-PRP, HA or saline solution, respectively. Six and twelve weeks later the rabbits were sacrificed and the samples were collected. The platelet number, the concentrations of growth factors of P-PRP and whole blood, and the IL-1β concentration in the joint fluid were investigated, and the histological assessment of the cartilage were performed according to Mankin's scoring system. Micro-CT was also used to evaluate the restoration of subchondral bone. The platelet concentration in P-PRP is 6.8 fold of that in the whole blood. The IL-1β level in the P-PRP group was lower than in the HA group (p<0.01 and in the control group (p<0.01. The restoration of the defected cartilage as well as the subchondral bone was better in the P-PRP group than in the HA group or the control group (P<0.05. Our data showed that P-PRP is better than HA in promoting the restoration of the cartilage and alleviating the arthritis caused by cartilage damage.

  16. Splicing Factor Prp8 Interacts With NES(AR) and Regulates Androgen Receptor in Prostate Cancer Cells.

    Science.gov (United States)

    Wang, Dan; Nguyen, Minh M; Masoodi, Khalid Z; Singh, Prabhpreet; Jing, Yifeng; O'Malley, Katherine; Dar, Javid A; Dhir, Rajiv; Wang, Zhou

    2015-12-01

    Androgen receptor (AR) plays a pivotal role in the development of primary as well as advanced castration-resistant prostate cancer. Previous work in our lab identified a novel nuclear export signal (NES) (NES(AR)) in AR ligand-binding domain essential for AR nucleocytoplasmic trafficking. By characterizing the localization of green fluorescence protein (GFP)-tagged NES(AR), we designed and executed a yeast mutagenesis screen and isolated 7 yeast mutants that failed to display the NES(AR) export function. One of those mutants was identified as the splicing factor pre-mRNA processing factor 8 (Prp8). We further showed that Prp8 could regulate NES(AR) function using short hairpin RNA knockdown of Prp8 coupled with a rapamycin export assay in mammalian cells and knockdown of Prp8 could induce nuclear accumulation of GFP-tagged AR in PC3 cells. Prp8 expression was decreased in castration-resistant LuCaP35 xenograft tumors as compared with androgen-sensitive xenografts. Laser capture microdissection and quantitative PCR showed Prp8 mRNA levels were decreased in human prostate cancer specimens with high Gleason scores. In prostate cancer cells, coimmunoprecipitation and deletion mutagenesis revealed a physical interaction between Prp8 and AR mainly mediated by NES(AR). Luciferase assay with prostate specific antigen promoter-driven reporter demonstrated that Prp8 regulated AR transcription activity in prostate cancer cells. Interestingly, Prp8 knockdown also increased polyubiquitination of endogenous AR. This may be 1 possible mechanism by which it modulates AR activity. These results show that Prp8 is a novel AR cofactor that interacts with NES(AR) and regulates AR function in prostate cancer cells.

  17. In vitro study of the role of thrombin in platelet rich plasma (PRP) preparation: utility for gel formation and impact in growth factors release.

    Science.gov (United States)

    Huber, Stephany Cares; Cunha Júnior, José Luiz Rosenberis; Montalvão, Silmara; da Silva, Letícia Queiroz; Paffaro, Aline Urban; da Silva, Francesca Aparecida Ramos; Rodrigues, Bruno Lima; Lana, José Fabio Santos Duarte; Annichino-Bizzacchi, Joyce Maria

    2016-01-01

    The use of PRP has been studied for different fields, with promising results in regenerative medicine. Until now, there is no study in the literature evaluating thrombin levels in serum, used as autologous thrombin preparation. Therefore, in the present study we evaluated the role played by different thrombin concentrations in PRP and the impact in the release of growth factors. Also, different activators for PRP gel formation were evaluated. Thrombin levels were measured in different autologous preparations: serum, L-PRP (PRP rich in leukocytes) and T-PRP (thrombin produced through PRP added calcium gluconate). L-PRP was prepared according to the literature, with platelets and leukocytes being quantified. The effect of autologous thrombin associated or not with calcium in PRP gel was determined by measuring the time of gel formation. The relationship between thrombin concentration and release of growth factors was determined by growth factors (PDGF-AA, VEGF and EGF) multiplex analysis. A similar concentration of thrombin was observed in serum, L-PRP and T-PRP (8.13 nM, 8.63 nM and 7.56 nM, respectively) with a high variation between individuals (CV%: 35.07, 43 and 58.42, respectively). T-PRP and serum with calcium chloride showed similar results in time to promote gel formation. The increase of thrombin concentrations (2.66, 8 and 24 nM) did not promote an increase in growth factor release. The technique of using serum as a thrombin source proved to be the most efficient and reproducible for promoting PRP gel formation, with some advantages when compared to other activation methods, as this technique is easier and quicker with no need of consuming part of PRP. Noteworthy, PRP activation using different thrombin concentrations did not promote a higher release of growth factors, appearing not to be necessary when PRP is used as a suspension.

  18. No effects of PRP on ultrasonographic tendon structure and neovascularisation in chronic midportion Achilles tendinopathy

    NARCIS (Netherlands)

    de Vos, R. J.; Weir, A.; Tol, J. L.; Verhaar, J. A. N.; Weinans, H.; van Schie, H. T. M.

    2011-01-01

    To assess whether a platelet-rich plasma (PRP) injection leads to an enhanced tendon structure and neovascularisation, measured with ultrasonographic techniques, in chronic midportion Achilles tendinopathy. Double-blind, randomised, placebo-controlled clinical trial. Sports medical department of The

  19. Acetylcholinesterase triggers the aggregation of PrP 106-126

    International Nuclear Information System (INIS)

    Pera, M.; Roman, S.; Ratia, M.; Camps, P.; Munoz-Torrero, D.; Colombo, L.; Manzoni, C.; Salmona, M.; Badia, A.; Clos, M.V.

    2006-01-01

    Acetylcholinesterase (AChE), a senile plaque component, promotes amyloid-β-protein (Aβ) fibril formation in vitro. The presence of prion protein (PrP) in Alzheimer's disease (AD) senile plaques prompted us to assess if AChE could trigger the PrP peptides aggregation as well. Consequently, the efficacy of AChE on the PrP peptide spanning-residues 106-126 aggregation containing a coumarin fluorescence probe (coumarin-PrP 106-126) was studied. Kinetics of coumarin-PrP 106-126 aggregation showed a significant increase of maximum size of aggregates (MSA), which was dependent on AChE concentration. AChE-PrP 106-126 aggregates showed the tinctorial and optical amyloid properties as determined by polarized light and electronic microscopy analysis. A remarkable inhibition of MSA was obtained with propidium iodide, suggesting that AChE triggers PrP 106-126 and Aβ aggregation through a similar mechanism. Huprines (AChE inhibitors) also significantly decreased MSA induced by AChE as well, unveiling the potential interest for some AChE inhibitors as a novel class of potential anti-prion drugs

  20. Comparison of the effect of activated or non-activated PRP in various concentrations on osteoblast and fibroblast cell line proliferation.

    Science.gov (United States)

    Vahabi, Surena; Yadegari, Zahra; Mohammad-Rahimi, Hossein

    2017-09-01

    Platelet-rich plasma (PRP) contains growth factors which positively affect cell proliferation, cell differentiation, chemotaxis and intracellular matrix synthesis. All these processes are involved in wound healing and tissue regeneration; thus, PRP as a source of growth factors can be used in periodontal regenerative therapies. The purpose of the present study was to assess the effect of various concentrations of activated and non-activated PRP on proliferation of osteoblasts and fibroblasts in vitro. PRP was obtained from three healthy volunteers. 75, 50, 25, and 10% concentrations of f PRP were prepared by dilution in Dulbecco's modified Eagle's medium. In activated PRP groups, PRP concentrations were activated by adding calcium gluconate. Human gingival fibroblast (HGF) cell line and MG-63 (osteosarcoma) human osteoblast-like cell line were used in the study. The MTT proliferation assay was used to assess the effect of different types of PRP concentrates on proliferation of HGF and MG-63 cells, in 24, 48 and 72 h. After 24, 48, and 72 h, the proliferation rate of both cell lines was higher in the positive control group, except in 72 h in HGF cell lines, that 10% non-activated PRP group and 10 and 25% activated PRP groups has higher proliferation rate than the positive control group, which it was not significant. Proliferation rate in cells with 10% activated PRP was highest among samples containing PRP. The current study failed to show the significant effect of activated or non-activated PRP on proliferation of HGFs or MG-63 osteoblast-like cells. However, our results showed that activated PRP had a greater effect than non-activated PRP.

  1. New energy paradigm?

    International Nuclear Information System (INIS)

    Goldoni, Giovanni

    2007-01-01

    The rise of oil prices, the difficulties in markets liberalization, and the poor results of competition have convinced many that a new energy paradigm is necessary. Taking the original definition of scientific paradigm, it doesn't seem that a practical solution could be found outside the present paradigm of energy policy, made of privatisation, liberalisation and competition [it

  2. Effect of platelet-rich plasma (PRP) concentration on proliferation, neurotrophic function and migration of Schwann cells in vitro.

    Science.gov (United States)

    Zheng, Canbin; Zhu, Qingtang; Liu, Xiaolin; Huang, Xijun; He, Caifeng; Jiang, Li; Quan, Daping; Zhou, Xiang; Zhu, Zhaowei

    2016-05-01

    Platelet-rich plasma (PRP) contains various growth factors and appears to have the potential to promote peripheral nerve regeneration, but evidence is lacking regarding its biological effect on Schwann cells (SCs). The present study was designed to investigate the effect of PRP concentration on SCs in order to determine the plausibility of using this plasma-derived therapy for peripheral nerve injury. PRP was obtained from rats by double-step centrifugation and was characterized by determining platelet numbers and growth factor concentrations. Primary cultures of rat SCs were exposed to various concentrations of PRP (40%, 20%, 10%, 5% and 2.5%). Cell proliferation assays and flow cytometry were performed to study to assess SC proliferation. Quantitative real-time PCR and ELISA analysis were performed to determine the ability of PRP to induce SCs to produce nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). Microchemotaxis assay was used to analyse the cell migration capacity. The results obtained indicated that the platelet concentration and growth factors in our PRP preparations were significantly higher than in whole blood. Cell culture experiments showed that 2.5-20% PRP significantly stimulated SC proliferation and migration compared to untreated controls in a dose-dependent manner. In addition, the expression and secretion of NGF and GDNF were significantly increased. However, the above effects of SCs were suppressed by high PRP concentrations (40%). In conclusion, the appropriate concentration of PRP had the potency to stimulate cell proliferation, induced the synthesis of neurotrophic factors and significantly increased migration of SCs dose-dependently. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

  3. Protein misfolding cyclic amplification induces the conversion of recombinant prion protein to PrP oligomers causing neuronal apoptosis.

    Science.gov (United States)

    Yuan, Zhen; Yang, Lifeng; Chen, Baian; Zhu, Ting; Hassan, Mohammad Farooque; Yin, Xiaomin; Zhou, Xiangmei; Zhao, Deming

    2015-06-01

    The formation of neurotoxic prion protein (PrP) oligomers is thought to be a key step in the development of prion diseases. Recently, it was determined that the sonication and shaking of recombinant PrP can convert PrP monomers into β-state oligomers. Herein, we demonstrate that β-state oligomeric PrP can be generated through protein misfolding cyclic amplification from recombinant full-length hamster, human, rabbit, and mutated rabbit PrP, and that these oligomers can be used for subsequent research into the mechanisms of PrP-induced neurotoxicity. We have characterized protein misfolding cyclic amplification-induced monomer-to-oligomer conversion of PrP from three species using western blotting, circular dichroism, size-exclusion chromatography, and resistance to proteinase K (PK) digestion. We have further shown that all of the resulting β-oligomers are toxic to primary mouse cortical neurons independent of the presence of PrP(C) in the neurons, whereas the corresponding monomeric PrP were not toxic. In addition, we found that this toxicity is the result of oligomer-induced apoptosis via regulation of Bcl-2, Bax, and caspase-3 in both wild-type and PrP(-/-) cortical neurons. It is our hope that these results may contribute to our understanding of prion transformation within the brain. We found that β-state oligomeric PrPs can be generated through protein misfolding cyclic amplification (PMCA) from recombinant full-length hamster, human, rabbit, and mutated rabbit PrP. β-oligomers are toxic to primary mouse cortical neurons independent of the presence of PrP(C) in the neurons, while the corresponding monomeric PrPs were not toxic. This toxicity is the result of oligomers-induced apoptosis via regulation of Bcl-2, Bax, and caspase-3. These results may contribute to our understanding of prion transformation within the brain. © 2015 International Society for Neurochemistry.

  4. Na+/K+-ATPase is present in scrapie-associated fibrils, modulates PrP misfolding in vitro and links PrP function and dysfunction.

    Directory of Open Access Journals (Sweden)

    James F Graham

    Full Text Available Transmissible spongiform encephalopathies are characterised by widespread deposition of fibrillar and/or plaque-like forms of the prion protein. These aggregated forms are produced by misfolding of the normal prion protein, PrP(C, to the disease-associated form, PrP(Sc, through mechanisms that remain elusive but which require either direct or indirect interaction between PrP(C and PrP(Sc isoforms. A wealth of evidence implicates other non-PrP molecules as active participants in the misfolding process, to catalyse and direct the conformational conversion of PrP(C or to provide a scaffold ensuring correct alignment of PrP(C and PrP(Sc during conversion. Such molecules may be specific to different scrapie strains to facilitate differential prion protein misfolding. Since molecular cofactors may become integrated into the growing protein fibril during prion conversion, we have investigated the proteins contained in prion disease-specific deposits by shotgun proteomics of scrapie-associated fibrils (SAF from mice infected with 3 different strains of mouse-passaged scrapie. Concomitant use of negative control preparations allowed us to identify and discount proteins that are enriched non-specifically by the SAF isolation protocol. We found several proteins that co-purified specifically with SAF from infected brains but none of these were reproducibly and demonstrably specific for particular scrapie strains. The α-chain of Na(+/K(+-ATPase was common to SAF from all 3 strains and we tested the ability of this protein to modulate in vitro misfolding of recombinant PrP. Na(+/K(+-ATPase enhanced the efficiency of disease-specific conversion of recombinant PrP suggesting that it may act as a molecular cofactor. Consistent with previous results, the same protein inhibited fibrillisation kinetics of recombinant PrP. Since functional interactions between PrP(C and Na(+/K(+-ATPase have previously been reported in astrocytes, our data highlight this molecule as

  5. Interaction between Shadoo and PrP Affects the PrP-Folding Pathway.

    Science.gov (United States)

    Ciric, Danica; Richard, Charles-Adrien; Moudjou, Mohammed; Chapuis, Jérôme; Sibille, Pierre; Daude, Nathalie; Westaway, David; Adrover, Miguel; Béringue, Vincent; Martin, Davy; Rezaei, Human

    2015-06-01

    Prion diseases are characterized by conformational changes of a cellular prion protein (PrP(C)) into a β-sheet-enriched and aggregated conformer (PrP(Sc)). Shadoo (Sho), a member of the prion protein family, is expressed in the central nervous system (CNS) and is highly conserved among vertebrates. On the basis of histoanatomical colocalization and sequence similarities, it is suspected that Sho and PrP may be functionally related. The downregulation of Sho expression during prion pathology and the direct interaction between Sho and PrP, as revealed by two-hybrid analysis, suggest a relationship between Sho and prion replication. Using biochemical and biophysical approaches, we demonstrate that Sho forms a 1:1 complex with full-length PrP with a dissociation constant in the micromolar range, and this interaction consequently modifies the PrP-folding pathway. Using a truncated PrP that mimics the C-terminal C1 fragment, an allosteric binding behavior with a Hill number of 4 was observed, suggesting that at least a tetramerization state occurs. A cell-based prion titration assay performed with different concentrations of Sho revealed an increase in the PrP(Sc) conversion rate in the presence of Sho. Collectively, our observations suggest that Sho can affect the prion replication process by (i) acting as a holdase and (ii) interfering with the dominant-negative inhibitor effect of the C1 fragment. Since the inception of the prion theory, the search for a cofactor involved in the conversion process has been an active field of research. Although the PrP interactome presents a broad landscape, candidates corresponding to specific criteria for cofactors are currently missing. Here, we describe for the first time that Sho can affect PrP structural dynamics and therefore increase the prion conversion rate. A biochemical characterization of Sho-PrP indicates that Sho acts as an ATP-independent holdase. Copyright © 2015, American Society for Microbiology. All Rights

  6. Tendinopathies and platelet-rich plasma (PRP: from pre-clinical experiments to therapeutic use

    Directory of Open Access Journals (Sweden)

    Kaux JF

    2015-05-01

    Full Text Available Objectives: The restorative properties of platelets, through the local release of growth factors, are used in various medical areas. This article reviews fundamental and clinical research relating to platelet-rich plasma applied to tendinous lesions. Materials and method: Articles in French and English, published between 1 January 2012 and 31 December 2014. dealing with PRP and tendons were searched for using the Medline and Scopus data bases. Results: Forty-seven articles were identified which addressed pre-clinical and clinical studies: 27 relating to in vitro and in vivo animal studies and 20 relating to human studies. Of these, five addressed lateral epicondylitis, two addressed rotator cuff tendinopathies, ten dealt with patellar tendinopathies and three looked at Achilles tendinopathies. Conclusions: The majority of pre-clinical studies show that PRP stimulates the tendon's healing process. However, clinical series remain more controversial and level 1, controlled, randomised studies are still needed.

  7. Platelet-rich plasma (PRP for the treatment of vulvar lichen sclerosus in a premenopausal woman: A case report

    Directory of Open Access Journals (Sweden)

    D. Franic

    2018-04-01

    Full Text Available The use of platelet-rich plasma (PRP for the treatment of lichen sclerosus (LS in a 38-year-old premenopausal woman is reported. The diagnosis was confirmed histologically and the symptoms documented using the ICIQ Vaginal Symptoms Questionnaire (ICIQ-VS and the Female Sexual Function Index (FSFI questionnaire. PRP was prepared from autologous blood using the Regen Cellular Matrix Kit. PRP was administered twice over two months. Histology at follow-up one month after the second administration showed the epidermis was nearly normal and upper dermal cellularity had been restored. The patient was symptom-free and both her ICIQ-VS and her FSFI scores had improved significantly. PRP is a potential new treatment option for LS which needs further assessment in randomized controlled trials. Keywords: Platelet-rich plasma, Vulvar lichen sclerosus, Premenopause, Treatment

  8. Using PRP and human amniotic fluid combination for osteogenesis in rabbit socket preservation

    Directory of Open Access Journals (Sweden)

    Amir Hossein Moradi

    2015-01-01

    Full Text Available Introduction: Platelet-rich plasma (PRP is used as an adjunct treatment during periodontal grafting surgery because of its capability of enhancing healing process. Amniotic fluid is a rich source of growth factors and hyaluronic acid (HA and a good point to study its properties of wound healing and bone formation. The aim of this study was to evaluate the osteogenic properties of a combination of amniotic fluid and PRP in rabbit′s dental socket preservation. Materials and Methods: The study population consisted of 24 healthy male laboratory rabbits (average weight 3,125 ± 185 gr that were randomly allocated into four groups. PRP for the first group, human amniotic fluid (HAF for the second group, a combination of PRP and HAF (PRHA for the third group was used. In the fourth (control group, no biomaterial was used. In each group, half of the rabbits were sacrificed at 4 weeks following surgery and the rest were sacrificed after 8 weeks. Histological analysis of biopsies of the sockets was performed using hematoxylin and eosin (H&E staining. Data were analyzed using Statistical Package for the Social Sciences (SPSS software (version 16 and P-value <0.05 was considered significance. Results: All three experimental groups showed positive effect on bone formation in terms of area of trabecular bone and number of osteocytes and also vessel formation. Socket preservation using HAF and PRHA showed the highest impact on bone formation. Socket preservation using HAF also had the highest impact on vessel formation. Conclusion: PRHA and HAF appear to be useful for enhancing bone formation. Since there was no difference between HAF and PRHA, it seems beneficial to use HAF due to its simplicity of application.

  9. Oxidation of Helix-3 methionines precedes the formation of PK resistant PrP.

    Directory of Open Access Journals (Sweden)

    Tamar Canello

    2010-07-01

    Full Text Available While elucidating the peculiar epitope of the alpha-PrP mAb IPC2, we found that PrPSc exhibits the sulfoxidation of residue M213 as a covalent signature. Subsequent computational analysis predicted that the presence of sulfoxide groups at both Met residues 206 and 213 destabilize the alpha-fold, suggesting oxidation may facilitate the conversion of PrPC into PrPSc. To further study the effect of oxidation on prion formation, we generated pAbs to linear PrP peptides encompassing the Helix-3 region, as opposed to the non-linear complexed epitope of IPC2. We now show that pAbs, whose epitopes comprise Met residues, readily detected PrPC, but could not recognize most PrPSc bands unless they were vigorously reduced. Next, we showed that the alpha-Met pAbs did not recognize newly formed PrPSc, as is the case for the PK resistant PrP present in lines of prion infected cells. In addition, these reagents did not detect intermediate forms such as PK sensitive and partially aggregated PrPs present in infected brains. Finally, we show that PrP molecules harboring the pathogenic mutation E200K, which is linked to the most common form of familial CJD, may be spontaneously oxidized. We conclude that the oxidation of methionine residues in Helix-3 represents an early and important event in the conversion of PrPC to PrPSc. We believe that further investigation into the mechanism and role of PrP oxidation will be central in finally elucidating the mechanism by which a normal cell protein converts into a pathogenic entity that causes fatal brain degeneration.

  10. Efectividad del PRP en el tratamiento de la artrosis de rodilla: Estudio de casos

    OpenAIRE

    Fernández Valverde, Noelia; Fidalgo González, Verónica

    2016-01-01

    La artrosis es una enfermedad degenerativa de elevada prevalencia para la cual, en la actualidad, no hay tratamiento curativo. Una de las localizaciones más frecuentes es la rodilla. La utilización de infiltraciones de plasma rico en plaquetas constituye una alternativa en el tratamiento de esta patología. Objetivo: demostrar la efectividad y la seguridad de las infiltraciones con PRP en el tratamiento de pacientes con artrosis de rodilla. Resultado: este trabajo muestra una...

  11. Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration

    Science.gov (United States)

    2013-01-01

    Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed

  12. Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration.

    Science.gov (United States)

    Albanese, Antonino; Licata, Maria E; Polizzi, Bianca; Campisi, Giuseppina

    2013-06-13

    Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed

  13. Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage.

    Science.gov (United States)

    Moussa, Mayssam; Lajeunesse, Daniel; Hilal, George; El Atat, Oula; Haykal, Gaby; Serhal, Rim; Chalhoub, Antonio; Khalil, Charbel; Alaaeddine, Nada

    2017-03-01

    Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1-2-3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. These results suggest that PRP could be a potential therapeutic tool for the treatment of OA. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. The role of PRP and adipose tissue-derived keratinocytes on burn wound healing in diabetic rats.

    Science.gov (United States)

    Hosseini Mansoub, Navid; Gürdal, Mehmet; Karadadaş, Elif; Kabadayi, Hilal; Vatansever, Seda; Ercan, Gulinnaz

    2018-01-01

    Introduction: Diabetic burn wounds and ulcers are significant complications of diabetic patients. The aim of this study is to investigate the use of platelet rich-plasma (PRP) and/or keratinocyte-like cells (KLCs) in diabetic thermal wound rat model and to evaluate EGF, FGF-2, TGF-β1, COL1α2, MCP-1 and VEGF-α as wound healing markers at gene expression level. Method: In this study, we used adipose tissue as the source of mesenchymal stem cells (MSCs) and differentiated MSCs into KLCs. KLCs were characterized and transferred to the burn areas on the dorsum of streptozotocine (STZ)-induced diabetic rats. We prepared PRP from rat blood and evaluated its effect alone or in combination with KLCs. On 3 rd , 7 th , 10 th and 14 th days after treatment, wound areas were measured and biopsy samples were excised from the wound areas of the KLCs and/or PRP-treated and untreated diabetic rats to analyze gene expression levels of wound healing markers by qPCR. Results: We observed that, wound contraction started earlier in the PRP and/or KLCs-treated groups in comparison to the control group. However, PRP and KLCs when applied in combination showed additive affect in wound healing. In all groups treated with KLCs and/or PRP, the gene expression levels of evaluated growth factors and COL1α2 increased, while MCP-1 levels decreased when compared to the untreated diabetic rats. In addition, the most prominent difference in qPCR results belongs to combined PRP and KLCs-treated group. Conclusion: We demonstrated that applying PRP and KLCs in combination has a greater potential for treatment of diabetic burn wounds.

  15. Platelet-rich plasma (PRP for acute muscle injury: a systematic review.

    Directory of Open Access Journals (Sweden)

    Mohamad Shariff A Hamid

    Full Text Available INTRODUCTION: Acute muscle injury is one of the commonest injuries that often result in loss of training and competition time. The best management for muscle injury has not been identified. Sports medicine practitioners used several approaches in attempt to accelerate time to recovery from muscle injury. More recently growing interest focussed on autologous blood product injection. METHODS: A literature search was conducted systematically using OvidMEDLINE, PubMed, EMBASE, SPORTDiscus and CINAHL databases to retrieve articles published until December 2012. Controlled trials and controlled laboratory studies comparing different strategies to promote early recovery of muscle injury were included. The methodological quality of studies was assessed. RESULTS: There are limited studies on the effects of PRP therapy for muscle injury. Three in vivo laboratory studies and one pilot human study were reviewed. The laboratory studies reported histological evidence on significant acceleration of muscle healing in animals treated with autologous conditioned serum (ACS, platelet-rich plasma (PRP and platelet rich fibrin matrix (PRFM. A pilot human study found athletes treated with repeated ACS injection recovers significantly faster than retrospective controls. CONCLUSION: Several in vivo laboratory studies suggest beneficial effects of ACS, PRP and PRFM in accelerating muscle recovery. Evidence to suggest similar effects on humans is however limited, as valuable information from robust human controlled trials is still not available at this moment. Hence, more studies of satisfactory methodological quality with platelet-rich plasma interventions on muscle injury are justified.

  16. Comparison between PRP, PRGF and PRF: lights and shadows in three similar but different protocols.

    Science.gov (United States)

    Giannini, S; Cielo, A; Bonanome, L; Rastelli, C; Derla, C; Corpaci, F; Falisi, G

    2015-01-01

    The main goal of the modern surgery is to get a low invasiveness and a high rate of clinical healing: in the last years, it has been introduced the concept of a "regenerative surgery", and many techniques has been widely described in the literature. The most used are PRP, PRGF and PRF techniques. Aim of this research is to compare the three protocol of PRP, PRF and PRGF in their essential features, so to suggest to the practitioners the best blood product to use in the regenerative surgery. Among the advantages that shows the PRF, compared to PRP and PRGF, we can cite a greater simplicity of production for the absence of manipulation that leads to a reduced possibility of alteration of the protocol due to an error of the operator. The special texture of the PRF and its biological features shows clearly an interesting surgical versatility and all the characteristics that can support a faster tissues regeneration and high-quality clinical outcomes.

  17. The Next Paradigm

    Directory of Open Access Journals (Sweden)

    Bernardo Kastrup

    2018-04-01

    Full Text Available In order to perceive the world, we need more than just raw sensory input: a subliminal paradigm of thought is required to interpret raw sensory data and, thereby, create the objects and events we perceive around ourselves. As such, the world we see reflects our own unexamined, culture-bound assumptions and expectations, which explains why every generation in history has believed that it more or less understood the world. Today, we perceive a world of objects and events outside and independent of mind, which merely reflects our current paradigm of thought. Anomalies that contradict this paradigm have been accumulated by physicists over the past couple of decades, which will eventually force our culture to move to a new paradigm. Under this new paradigm, a form of universal mind will be viewed as nature’s sole fundamental entity. In this paper, I offer a sketch of what the new paradigm may look like.

  18. In Vitro Studies on the Degradability, Bioactivity, and Cell Differentiation of PRP/AZ31B Mg Alloys Composite Scaffold

    Directory of Open Access Journals (Sweden)

    Jian Zou

    2017-01-01

    Full Text Available In recent years, more and more methods have been developed to improve the bioactivity of the biodegradable materials in bone tissue regeneration. In present study, we used rat mesenchymal stem cells (rMSCs to evaluate the outcomes of Mg alloys (AZ31B, Magnesium, and Aluminum and Platelet-rich plasma (PRP/Mg alloys on rMSCs biocompatibility and osteogenic differentiation. Water absorption experiments indicated that both bare AZ31B and PRP/AZ31B were capable of absorbing large amounts of water. But the water absorption ratio for PRP/AZ31B was significantly higher than that for bare AZ31B. The degradability experiments implied that both samples degraded at same speed. rMSCs on the surface of AZ31B distributed more and better than those on the AZ31B scaffold. In ALP activity experiment, the activity of rMSCs on the PRP/AZ31B was markedly higher than that on the AZ31B scaffolds on the 7th day and 14th day. qRT-PCR also showed that OPN and OCN were expressed in both samples. OPN and OCN expression in PRP/AZ31B sample were higher than those in bare AZ31B samples. In summary, the in vitro study implied that AZ31B combined with PRP could remarkably improve cell seeding, attachment, proliferation, and differentiation.

  19. Didaktiske paradigmer og refleksion

    DEFF Research Database (Denmark)

    Christensen, Torben Spanget

    2014-01-01

    analysis of subject didactics by Sigmund Ongstad. The two positions offer fundamentally different insights into didactics. Nielsen’s position establishes didactics as a knowledge domain and Ongstad’s position points to the dynamics of subject didactics by analyzing communication as a basic aspect. Krogh...... this article. A possible utilitarian didactical paradigm, already indicated by Krogh as a historical paradigm prominent in our time, is also discussed. It is suggested that reflection could be seen as a normative response to the utilitarian paradigm, and not as a paradigm in its own right. It is concluded...

  20. Tratamiento de quemaduras mediante plasma rico en plaquetas (PRP: parte I

    Directory of Open Access Journals (Sweden)

    G. Rossani

    2014-06-01

    Full Text Available El objetivo del presente trabajo es determinar la eficacia clínica del plasma rico en plaquetas (PRP en las quemaduras de segundo grado. Estudiamos el tiempo requerido en la reepitelización del tejido dañado, la estancia hospitalaria asociada a la curación de las lesiones y la satisfacción del paciente. Realizamos un estudio prospectivo, observacional y longitudinal, en una muestra de 115 pacientes con quemaduras de segundo grado según la clasificación de Converse-Smith. Las lesiones fueron de menos de 48 horas de evolución, en diferentes zonas de cara y cuerpo. A todos los pacientes se les aplicó de forma ambulatoria PRP por goteo, completándose el tratamiento con la aplicación de gasas parafinadas. El estudio se realizó entre marzo de 2011 y agosto de 2013. Las quemaduras que evolucionaron mejor y de forma más rápida fueron las de cara, seguidas por las de abdomen y, por último, las de extremidades inferiores. En todas, el tiempo de epitelización fue un 30 % inferior que en quemaduras de similar extensión, profundidad y localización, en pacientes anteriormente tratados sin PRP. Los pacientes fueron atendidos ambulatoriamente cuando las lesiones lo permitieron, y si presentaban lesiones más extensas fueron hospitalizados. El tiempo de internamiento en estos casos se redujo como promedio 18 días con respecto al grupo no tratado con PRP. El tiempo de reepitelización, estancia hospitalaria y la satisfacción de los pacientes, alcanzaron significación estadística p< 0,05. En conclusión, creemos que el uso de PRP acorta el tiempo de recuperación en quemaduras de segundo grado, reduce el tiempo de hospitalización y conlleva un alto grado de satisfacción de los pacientes por los resultados obtenidos.

  1. PrP P102L and Nearby Lysine Mutations Promote Spontaneous In Vitro Formation of Transmissible Prions.

    Science.gov (United States)

    Kraus, Allison; Raymond, Gregory J; Race, Brent; Campbell, Katrina J; Hughson, Andrew G; Anson, Kelsie J; Raymond, Lynne D; Caughey, Byron

    2017-11-01

    Accumulation of fibrillar protein aggregates is a hallmark of many diseases. While numerous proteins form fibrils by prion-like seeded polymerization in vitro , only some are transmissible and pathogenic in vivo To probe the structural features that confer transmissibility to prion protein (PrP) fibrils, we have analyzed synthetic PrP amyloids with or without the human prion disease-associated P102L mutation. The formation of infectious prions from PrP molecules in vitro has required cofactors and/or unphysiological denaturing conditions. Here, we demonstrate that, under physiologically compatible conditions without cofactors, the P102L mutation in recombinant hamster PrP promoted prion formation when seeded by minute amounts of scrapie prions in vitro Surprisingly, combination of the P102L mutation with charge-neutralizing substitutions of four nearby lysines promoted spontaneous prion formation. When inoculated into hamsters, both of these types of synthetic prions initiated substantial accumulation of prion seeding activity and protease-resistant PrP without transmissible spongiform encephalopathy (TSE) clinical signs or notable glial activation. Our evidence suggests that PrP's centrally located proline and lysine residues act as conformational switches in the in vitro formation of transmissible PrP amyloids. IMPORTANCE Many diseases involve the damaging accumulation of specific misfolded proteins in thread-like aggregates. These threads (fibrils) are capable of growing on the ends by seeding the refolding and incorporation of the normal form of the given protein. In many cases such aggregates can be infectious and propagate like prions when transmitted from one individual host to another. Some transmitted aggregates can cause fatal disease, as with human iatrogenic prion diseases, while other aggregates appear to be relatively innocuous. The factors that distinguish infectious and pathogenic protein aggregates from more innocuous ones are poorly understood

  2. Dynamic paradigm of turbulence

    International Nuclear Information System (INIS)

    Mukhamedov, Alfred M.

    2006-01-01

    In this paper a dynamic paradigm of turbulence is proposed. The basic idea consists in the novel definition of chaotic structure given with the help of Pfaff system of PDE associated with the turbulent dynamics. A methodological analysis of the new and the former paradigm is produced

  3. An Integrative Paradigm

    Science.gov (United States)

    Hammack, Phillip L.

    2005-01-01

    Through the application of life course theory to the study of sexual orientation, this paper specifies a new paradigm for research on human sexual orientation that seeks to reconcile divisions among biological, social science, and humanistic paradigms. Recognizing the historical, social, and cultural relativity of human development, this paradigm…

  4. Prion Propagation in Cells Expressing PrP Glycosylation Mutants ▿

    Science.gov (United States)

    Salamat, Muhammad K.; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

    2011-01-01

    Infection by prions involves conversion of a host-encoded cell surface protein (PrPC) to a disease-related isoform (PrPSc). PrPC carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrPC glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrPSc and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrPSc, while PrPC with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrPC, were able to form infectious PrPSc. Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection. PMID:21248032

  5. Of Paradigms and Power

    DEFF Research Database (Denmark)

    Carstensen, Martin B.; Matthijs, Matthias

    in the study of policy paradigms. To demonstrate the general applicability of our framework, the paper examines the evolution of British macroeconomic policy making since 1990. We show that various Prime Ministers and their Chancellors were able to reinterpret and redefine the dominant neoliberal understanding......? Despite the profound impact of Peter Hall’s approach to policy paradigms and social learning, there is a burgeoning consensus that transposing a rudimentary ‘Kuhnian’ understanding of paradigms into the context of public policy making leads to a notion of punctuated equilibrium style shifts as the only...

  6. Tratamiento de quemaduras mediante plasma rico en plaquetas (PRP): parte I

    OpenAIRE

    G. Rossani; I. Hernández; J.M. Alcolea; R. Castro-Sierra; W. Pérez-Soto; M.A. Trelles

    2014-01-01

    El objetivo del presente trabajo es determinar la eficacia clínica del plasma rico en plaquetas (PRP) en las quemaduras de segundo grado. Estudiamos el tiempo requerido en la reepitelización del tejido dañado, la estancia hospitalaria asociada a la curación de las lesiones y la satisfacción del paciente. Realizamos un estudio prospectivo, observacional y longitudinal, en una muestra de 115 pacientes con quemaduras de segundo grado según la clasificación de Converse-Smith. Las lesiones fueron ...

  7. Platelet-Rich Plasma (PRP) Rinses for the Treatment of Non-Responding Oral Lichen Planus: A Case Report.

    Science.gov (United States)

    Merigo, Elisabetta; Oppici, Aldo; Parlatore, Anna; Cella, Luigi; Clini, Fabio; Fontana, Matteo; Fornaini, Carlo

    2018-02-06

    Platelet-rich plasma (PRP) has been proposed for different applications in the medical field and in maxillofacial surgery thanks to its many growth factors, such as epidermal growth factor (EGF), fibroblast growth factor (FGF), and keratinocyte growth factor (KGF). Oral lichen planus (OLP) is a disease that affects the oral mucosa in a chronic way. This disease frequently worsens the quality of life of patients, particularly when clinical manifestations are of the erythematous or erosive/ulcerative type. The properties of PRP that are supported by scientific literature in both oral medicine and other medical fields have suggested the introduction of PRP in clinical practice for the medical treatment of different soft tissues diseases, such as when OLP patients do not respond to conventional therapies, or when conventional treatments have some contraindications or side effects. The aim of this work is to describe the use of PRP used as an oral rinse for the treatment of a patient diagnosed as affected by OLP at the Dentistry, Special Needs and Maxillo-Facial Surgery Unit of the Hospital of Piacenza. PRP protocol was started after the failure of conventional therapies based on the use of topical and systemic corticosteroids, hydroxychloroquine, and low-level laser therapy applications.

  8. Truncated forms of the prion protein PrP demonstrate the need for complexity in prion structure

    Energy Technology Data Exchange (ETDEWEB)

    Wan, William; Stöhr, Jan; Kendall, Amy; Stubbs, Gerald

    2015-09-01

    Self-propagation of aberrant protein folds is the defining characteristic of prions. Knowing the structural basis of self-propagation is essential to understanding prions and their related diseases. Prion rods are amyloid fibrils, but not all amyloids are prions. Prions have been remarkably intractable to structural studies, so many investigators have preferred to work with peptide fragments, particularly in the case of the mammalian prion protein PrP. We compared the structures of a number of fragments of PrP by X-ray fiber diffraction, and found that although all of the peptides adopted amyloid conformations, only the larger fragments adopted conformations that modeled the complexity of self-propagating prions, and even these fragments did not always adopt the PrP structure. It appears that the relatively complex structure of the prion form of PrP is not accessible to short model peptides, and that self-propagation may be tied to a level of structural complexity unobtainable in simple model systems. The larger fragments of PrP, however, are useful to illustrate the phenomenon of deformed templating (heterogeneous seeding), which has important biological consequences.

  9. Truncated forms of the prion protein PrP demonstrate the need for complexity in prion structure.

    Science.gov (United States)

    Wan, William; Stöhr, Jan; Kendall, Amy; Stubbs, Gerald

    2015-01-01

    Self-propagation of aberrant protein folds is the defining characteristic of prions. Knowing the structural basis of self-propagation is essential to understanding prions and their related diseases. Prion rods are amyloid fibrils, but not all amyloids are prions. Prions have been remarkably intractable to structural studies, so many investigators have preferred to work with peptide fragments, particularly in the case of the mammalian prion protein PrP. We compared the structures of a number of fragments of PrP by X-ray fiber diffraction, and found that although all of the peptides adopted amyloid conformations, only the larger fragments adopted conformations that modeled the complexity of self-propagating prions, and even these fragments did not always adopt the PrP structure. It appears that the relatively complex structure of the prion form of PrP is not accessible to short model peptides, and that self-propagation may be tied to a level of structural complexity unobtainable in simple model systems. The larger fragments of PrP, however, are useful to illustrate the phenomenon of deformed templating (heterogeneous seeding), which has important biological consequences.

  10. Platelet-Rich Plasma (PRP Rinses for the Treatment of Non-Responding Oral Lichen Planus: A Case Report

    Directory of Open Access Journals (Sweden)

    Elisabetta Merigo

    2018-02-01

    Full Text Available Platelet-rich plasma (PRP has been proposed for different applications in the medical field and in maxillofacial surgery thanks to its many growth factors, such as epidermal growth factor (EGF, fibroblast growth factor (FGF, and keratinocyte growth factor (KGF. Oral lichen planus (OLP is a disease that affects the oral mucosa in a chronic way. This disease frequently worsens the quality of life of patients, particularly when clinical manifestations are of the erythematous or erosive/ulcerative type. The properties of PRP that are supported by scientific literature in both oral medicine and other medical fields have suggested the introduction of PRP in clinical practice for the medical treatment of different soft tissues diseases, such as when OLP patients do not respond to conventional therapies, or when conventional treatments have some contraindications or side effects. The aim of this work is to describe the use of PRP used as an oral rinse for the treatment of a patient diagnosed as affected by OLP at the Dentistry, Special Needs and Maxillo-Facial Surgery Unit of the Hospital of Piacenza. PRP protocol was started after the failure of conventional therapies based on the use of topical and systemic corticosteroids, hydroxychloroquine, and low-level laser therapy applications.

  11. Programming Language Paradigms

    OpenAIRE

    Felician ALECU

    2013-01-01

    This paper's goal is to briefly explain the basic theory behind programming languages and their history while taking a close look at different programming paradigms that are used today as well as describing their differences, benefits, and drawbacks

  12. Paradigms and pragmatism: approaches to medical statistics.

    Science.gov (United States)

    Healy, M J

    2000-01-01

    Until recently, the dominant philosophy of science was that due to Karl Popper, with its doctrine that the proper task of science was the formulation of hypotheses followed by attempts at refuting them. In spite of the close analogy with significance testing, these ideas do not fit well with the practice of medical statistics. The same can be said of the later philosophy of Thomas Kuhn, who maintains that science proceeds by way of revolutionary upheavals separated by periods of relatively pedestrian research which are governed by what Kuhn refers to as paradigms. Through there have been paradigm shifts in the history of statistics, a degree of continuity can also be discerned. A current paradigm shift is embodied in the spread of Bayesian ideas. It may be that a future paradigm will emphasise the pragmatic approach to statistics that is associated with the name of Daniel Schwartz.

  13. Protecting effect of PrP codons M142 and K222 in goats orally challenged with bovine spongiform encephalopathy prions.

    Science.gov (United States)

    Fast, C; Goldmann, W; Berthon, P; Tauscher, K; Andréoletti, O; Lantier, I; Rossignol, C; Bossers, A; Jacobs, J G; Hunter, N; Groschup, M H; Lantier, F; Langeveld, J P M

    2017-09-19

    Breeding towards genetic resistance to prion disease is effective in eliminating scrapie. In sheep, classical forms of scrapie have been eradicated almost completely in several countries by breeding programs using a prion protein (PrP) gene (PRNP) amino acid polymorphism. For goats, field and experimental studies have provided evidence for several amino acid polymorphisms that are associated with resistance to scrapie, but only limited data are available concerning the susceptibility of caprine PRNP genotypes to BSE. In this study, goat kids representing five PRNP genotypes based on three polymorphisms (M142, Q211 and K222 and the wild type I142, R211 and Q222) were orally challenged with bovine or goat BSE. Wild type goats were killed with clinical signs between 24-28 months post inoculation (mpi) to both challenges, and goats with genotype R/Q211 succumbed between 29-36 mpi. I/M142 goats developed clinical signs at 44-45 mpi and M/M142 goats remained healthy until euthanasia at 48 mpi. None of the Q/K222 goats showed definite clinical signs. Taken together the highest attack ratios were seen in wild type and R/Q211 goats, and the lowest in I/M142, M/M142 and Q/K222. In all genotype groups, one or more goats remained healthy within the incubation period in both challenges and without detectable PrP deposition in the tissues. Our data show that both the K222 and M142 polymorphisms lengthen the incubation period significantly compared to wild type animals, but only K222 was associated with a significant increase in resistance to BSE infection after oral exposure to both BSE sources.

  14. A DTAP–IPV//PRP~T VACCINE: A REVIEW OF 16 YEARS’ CLINICAL EXPERIENCE

    Directory of Open Access Journals (Sweden)

    Stanley A. Plotkin

    2012-01-01

    Full Text Available Owing to their low reactogenicity, confirmed efficacy and availability in combination vaccines, acellular pertussis (aP-inactivated poliovirus (IPV combined vaccines are now included in various national immunization programs worldwide. We provide an overview of 16 years of clinical experience with a diphtheria (D, tetanus (T, aP, IPV and Haemophilus influenzae type b (Hib polysaccharide conjugated to tetanus protein (PRP~T combined vaccine (DTaP–IPV//PRP~T — Pentaxim, Sanofi Pasteur, France. Good immunogenicity has been demonstrated after primary vaccination with Pentaxim, regardless of the population ethnicity and primary vaccination schedule. A booster vaccination in the second year of life also resulted in a high immune response for each antigen. Furthermore, 10 years of national surveillance in Sweden has demonstrated the effectiveness of Pentaxim in controlling pertussis. As is the case for other aP-containing combined vaccines, Pentaxim is well tolerated, with the safety profile being better than for whole-cell pertussiscontaining combination vaccines for primary and booster vaccinations.

  15. Prediction and optimization of the recovery rate in centrifugal separation of platelet-rich plasma (PRP)

    Science.gov (United States)

    Piao, Linfeng; Park, Hyungmin; Jo, Chris

    2016-11-01

    We present a theoretical model of the recovery rate of platelet and white blood cell in the process of centrifugal separation of platelet-rich plasma (PRP). For the practically used conditions in the field, the separation process is modeled as a one-dimensional particle sedimentation; a quasi-linear partial differential equation is derived based on the kinematic-wave theory. This is solved to determine the interface positions between supernatant-suspension and suspension-sediment, used to estimate the recovery rate of the plasma. While correcting the Brown's hypothesis (1989) claiming that the platelet recovery is linearly proportional to that of plasma, we propose a new correlation model for prediction of the platelet recovery, which is a function of the volume of whole blood, centrifugal acceleration and time. For a range of practical parameters, such as hematocrit, volume of whole blood and centrifugation (time and acceleration), the predicted recovery rate shows a good agreement with available clinical data. We propose that this model is further used to optimize the preparation method of PRP that satisfies the customized case. Supported by a Grant (MPSS-CG-2016-02) through the Disaster and Safety Management Institute funded by Ministry of Public Safety and Security of Korean government.

  16. PRP Comments for ICF Q1/Q2 FY17 Experiments 3/10/16

    Energy Technology Data Exchange (ETDEWEB)

    Kauffman, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-04-14

    The PRP generally endorsed the Program plan during the short time for discussions. We agree that the strategy to develop a hohlraum that is symmetric and has low laser-plasma instabilities and to develop an alternative method for supporting the capsule is the best path forward for making progress in understanding ignition performance. The Program is oriented toward a milestone in 2020 for “determining the efficacy of NIF for ignition and credible physics-scaling to multi-megajoule yields for all ICF approaches.” We are concerned that the time and resources are not sufficient to vet all of the various approaches that are being pursued to make an informed decision by this date. For NIF to meet this goal, a process will be needed to to select the most promising paths forward. We recommend that the Program develop this process for selecting the path forward to optimize resources. We were glad to see that the direct drive program took our comments under consideration. We think that the proposed experiments have the program headed in a better direction. The PRP had only a short time to discuss the detailed experimental proposals. The following are comments on the detailed proposals. We did not have time to discuss them as a group. They represent individual opinions and provided to you as feedback to your proposals.

  17. A modified three-term PRP conjugate gradient algorithm for optimization models.

    Science.gov (United States)

    Wu, Yanlin

    2017-01-01

    The nonlinear conjugate gradient (CG) algorithm is a very effective method for optimization, especially for large-scale problems, because of its low memory requirement and simplicity. Zhang et al. (IMA J. Numer. Anal. 26:629-649, 2006) firstly propose a three-term CG algorithm based on the well known Polak-Ribière-Polyak (PRP) formula for unconstrained optimization, where their method has the sufficient descent property without any line search technique. They proved the global convergence of the Armijo line search but this fails for the Wolfe line search technique. Inspired by their method, we will make a further study and give a modified three-term PRP CG algorithm. The presented method possesses the following features: (1) The sufficient descent property also holds without any line search technique; (2) the trust region property of the search direction is automatically satisfied; (3) the steplengh is bounded from below; (4) the global convergence will be established under the Wolfe line search. Numerical results show that the new algorithm is more effective than that of the normal method.

  18. Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP versus Hyaluronic Acid (A one-year randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Seyed Ahmad Raeissadat

    2015-01-01

    Full Text Available Introduction Knee osteoarthritis (OA is the most common articular disease. Different methods are used to alleviate the symptoms of patients with knee OA, including analgesics, physical therapy, exercise prescription, and intra-articular injections (glucocorticoids, hyaluronic acid [HA], etc. New studies have focused on modern therapeutic methods that stimulate cartilage healing process and improve the damage, including the use of platelet-rich plasma (PRP as a complex of growth factors. Due to the high incidence of OA and its consequences, we decided to study the long-term effect of intraarticular injection of PRP and HA on clinical outcome and quality of life of patients with knee OA. Method This non-placebo-controlled randomized clinical trial involved 160 patients affected by knee OA, grade 1–4 of Kellgren–Lawrence scale. In the PRP group ( n = 87, two intra-articular injections at 4-week interval were applied, and in the HA group ( n = 73, three doses of intra-articular injection at 1-week interval were applied. All patients were prospectively evaluated before and at 12 months after the treatment by Western Ontario and McMaster Universities Arthritis Index (WOMAC and SF-36 questionnaires. The results were analyzed using SPSS 16.1 software (RCT code: IRCT2014012113442N5. Results At the 12-month follow-up, WOMAC pain score and bodily pain significantly improved in both groups; however, better results were determined in the PRP group compared to the HA group ( P < 0.001. Other WOMAC and SF-36 parameters improved only in the PRP group. More improvement (but not statistically significant was achieved in patients with grade 2 OA in both the groups. Conclusion This study suggests that PRP injection is more efficacious than HA injection in reducing symptoms and improving quality of life and is a therapeutic option in select patients with knee OA who have not responded to conventional treatment.

  19. Platelet rich Plasma in Achilles Tendon Healing 2 (PATH-2) trial: protocol for a multicentre, participant and assessor-blinded, parallel-group randomised clinical trial comparing platelet-rich plasma (PRP) injection versus placebo injection for Achilles tendon rupture.

    Science.gov (United States)

    Alsousou, Joseph; Keene, David J; Hulley, Philippa A; Harrison, Paul; Wagland, Susan; Byrne, Christopher; Schlüssel, Michael Maia; Dutton, Susan J; Lamb, Sarah E; Willett, Keith

    2017-11-16

    Achilles tendon injuries give rise to substantial long-lasting morbidity and pose considerable challenges for clinicians and patients during the lengthy healing period. Current treatment strategies struggle to curb the burden of this injury on health systems and society due to lengthy rehabilitation, work absence and reinjury risk. Platelet-rich plasma (PRP) is an autologous preparation that has been shown to improve the mechanobiological properties of tendons in laboratory and animal studies. The use of PRP in musculoskeletal injuries is on the increase despite the lack of adequately powered clinical studies. This is a multicentre randomised controlled trial to evaluate the efficacy and mechanism of PRP in patients with acute Achilles tendon rupture (ATR). All adults with acute ATR presenting within 12 days of the injury who are to be treated non-operatively are eligible. A total of 230 consenting patients will be randomly allocated via a remote web-based service to receive PRP injection or placebo injection to the site of the injury. All participants will be blinded to the intervention and will receive standardised rehabilitation to reduce efficacy interference.Participants will be followed up with blinded assessments of muscle-tendon function, quality of life, pain and overall patient's functional goals at 4, 7, 13, 24 weeks and 24 months post-treatment. The primary outcome is the heel-rise endurance test (HRET), which will be supervised by a blinded assessor at 24 weeks. A subgroup of 16 participants in one centre will have needle biopsy under ultrasound guidance at 6 weeks. Blood and PRP will be analysed for cell count, platelet activation and growth factor concentrations. The protocol has been approved by the Oxfordshire Research Ethics Committee (Oxfordshire Research Ethics Committee A, reference no 14/SC/1333). The trial will be reported in accordance with the CONSORT statement and published in peer-reviewed scientific journals. ISRCTN: 54992179, assigned

  20. On the extent of homogeneity region of PrP phase in the system praseodymium-phosphorus

    International Nuclear Information System (INIS)

    Mironov, K.E.

    1984-01-01

    For constructed by ion type compounds in the metal or metalloid systems homogeneity region boundary position can be observed at different compositions depending on which side the approximation to it occurs: on the metal or compound side. As an example the PrP homogeneity region in the praseodymium-phosphorus system is considered. An assumption is made on the prevalence of this phenomenon among rare earth monopnictides and monochalcogenides. For the PrP phase it is indicated that the monophopshide cell parameter depends on content of impurities in the initial metal, oxygen, in particular

  1. Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Moussa, Mayssam, E-mail: Moussa-mayssam@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Lajeunesse, Daniel, E-mail: daniel.lajeunesse@umontreal.ca [Research Centre in Osteoarthritis, Research Centre in Monteral University (Canada); Hilal, George, E-mail: George2266@gmail.com [Cancer and metabolism Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); El Atat, Oula, E-mail: oulaatat@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Haykal, Gaby, E-mail: Gaby.haykal@hdf.usj.edu.lb [Hotel Dieu de France, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Serhal, Rim, E-mail: rim.basbous@gmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Chalhoub, Antonio, E-mail: Mava.o@hotmail.com [Carantina Hospital, Beirut (Lebanon); Khalil, Charbel, E-mail: charbelk3@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Alaaeddine, Nada, E-mail: Nada.aladdin@gmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon)

    2017-03-01

    Objectives: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. Methods: Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1–2–3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. Results: PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. Conclusion: These results suggest that PRP could be a potential therapeutic tool for the treatment of OA. - Highlights: • Platelet Rich Plasma is suggested as a new treatment for osteoarthritis. • The proposed therapeutic effect is

  2. Oxidation reduces the fibrillation but not the neurotoxicity of the prion peptide PrP106-126

    DEFF Research Database (Denmark)

    Bergstrøm, Linda Alice; Chabry, J.; Bastholm, L.

    2007-01-01

    There is increasing evidence that soluble oligomers of misfolded protein may play a role in the pathogenesis of protein misfolding diseases including the transmissible spongiform encephalopathies (TSE) where the protein involved is the prion protein, PrP. The effect of oxidation on fibrillation...... tendency and neurotoxicity of different molecular variants of the prion peptide PrP106-126 was investigated. It was found that methionine oxidation significantly reduced amyloid fibril formation and proteinase K resistance, but it did not reduce (but rather increase slightly) the neurotoxicity...

  3. Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage

    International Nuclear Information System (INIS)

    Moussa, Mayssam; Lajeunesse, Daniel; Hilal, George; El Atat, Oula; Haykal, Gaby; Serhal, Rim; Chalhoub, Antonio; Khalil, Charbel; Alaaeddine, Nada

    2017-01-01

    Objectives: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. Methods: Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1–2–3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. Results: PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. Conclusion: These results suggest that PRP could be a potential therapeutic tool for the treatment of OA. - Highlights: • Platelet Rich Plasma is suggested as a new treatment for osteoarthritis. • The proposed therapeutic effect is

  4. PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry.

    Science.gov (United States)

    Maréchal, Alexandre; Li, Ju-Mei; Ji, Xiao Ye; Wu, Ching-Shyi; Yazinski, Stephanie A; Nguyen, Hai Dang; Liu, Shizhou; Jiménez, Amanda E; Jin, Jianping; Zou, Lee

    2014-01-23

    PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). Although the role for PRP19 in splicing is well characterized, its role in the DDR remains elusive. Through a proteomic screen for proteins that interact with RPA-coated single-stranded DNA (RPA-ssDNA), we identified PRP19 as a sensor of DNA damage. PRP19 directly binds RPA and localizes to DNA damage sites via RPA, promoting RPA ubiquitylation in a DNA-damage-induced manner. PRP19 facilitates the accumulation of ATRIP, the regulatory partner of the ataxia telangiectasia mutated and Rad3-related (ATR) kinase, at DNA damage sites. Depletion of PRP19 compromised the phosphorylation of ATR substrates, recovery of stalled replication forks, and progression of replication forks on damaged DNA. Importantly, PRP19 mutants that cannot bind RPA or function as an E3 ligase failed to support the ATR response, revealing that PRP19 drives ATR activation by acting as an RPA-ssDNA-sensing ubiquitin ligase during the DDR. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. A Comparison of Platelet Count and Enrichment Percentages in the Platelet Rich Plasma (PRP) Obtained Following Preparation by Three Different Methods.

    Science.gov (United States)

    Sabarish, Ram; Lavu, Vamsi; Rao, Suresh Ranga

    2015-02-01

    Platelet rich plasma (PRP) represents an easily accessible and rich source of autologous growth factors. Different manual methods for the preparation of PRP have been suggested. Lacuna in knowledge exists about the efficacy of PRP preparation by these different manual methods. This study was performed to determine the effects of centrifugation rate revolutions per minute (RPM) and time on the platelet count and enrichment percentages in the concentrates obtained following the three different manual methods of PRP preparation. In vitro experimental study. This was an experimental study in which platelet concentration was assessed in the PRP prepared by three different protocols as suggested by Marx R (method 1), Okuda K (method 2) and Landesberg R (method 3). A total of 60 peripheral blood samples, (n=20 per method) were obtained from healthy volunteers. Baseline platelet count was assessed for all the subjects following which PRP was prepared. The platelet count in the PRP was determined using coulter counter (Sysmex XT 2000i). The mean of the platelet count obtained and their enrichment percentage were calculated and intergroup comparison was done (Tukey's HSD test). The number of platelets and enrichment percentage in PRP prepared by method 1 was higher compared to method 2 and method 3; this difference in platelet concentrates was found to be statistically significant (p < 0.05). The centrifugation rate and time appear to be important parameters, which influence the platelet yield. Method 1 which had lower centrifugation rate and time yielded a greater platelet count and enrichment percentage.

  6. The application of PRP combined with TCP in repairing avascular necrosis of the femoral head after femoral neck fracture in rabbit.

    Science.gov (United States)

    Zhang, X-L; Wang, Y-M; Chu, K; Wang, Z-H; Liu, Y-H; Jiang, L-H; Chen, X; Zhou, Z-Y; Yin, G

    2018-02-01

    In view of the high occurrence of avascular necrosis of the femoral head (ANFH) after femoral neck fracture and the difficulties in the treatment, our work aimed to explore the effects of platelet-rich plasma (PRP) combined with tri-calcium phosphate (TCP) on the repair of ANFH after femoral neck fracture and to provide reference for clinical treatment. Thirty New Zealand white rabbits were randomly divided into control group, TCP group, and PRP+TCP group. The rabbit ANFH model was established and femoral head tissues were collected. HE staining was used for histological observation. Image analysis and statistical analysis were used to calculate the New Bone Area fraction (NBA %). The levels of bone morphogenetic protein (BMP)-7, transforming growth factor (TGF)-β1, basic fibroblast growth factor (bFGF), interleukin (IL)-6 and tumor necrosis factor (TNF)-a in serum were detected by Enzyme-Linked ImmunoSorbent Assay (ELISA). The new bone area of TCP group was significantly lower than that of PRP+TCP group (pPRP+TCP groups (pPRP+TCP group was higher than that in TCP group. TCP and PRP+TCP can both significantly reduce the content of IL-6 and TNF-a (pPRP+TCP group compared with the TCP group at 8 weeks after injection. PRP combined with TCP, which can promote new bone formation and inhibit inflammatory response, showed higher efficiency in repairing ANFH than internal fixation alone.

  7. PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice

    NARCIS (Netherlands)

    McBride, P. A.; Eikelenboom, P.; Kraal, G.; Fraser, H.; Bruce, M. E.

    1992-01-01

    Abnormal forms of a host protein, PrP, accumulate in the central nervous system in scrapie-affected animals. Here, PrP protein was detected immunocytochemically in tissue sections of spleen, lymph node, Peyer's patches, thymus, and pancreas from uninfected mice and from mice infected with a range of

  8. Investigation of modified platelet-rich plasma (mPRP in promoting the proliferation and differentiation of dental pulp stem cells from deciduous teeth

    Directory of Open Access Journals (Sweden)

    J. Wen

    2016-01-01

    Full Text Available Stem cells from human exfoliated deciduous teeth (SHEDs have great potential to treat various dental-related diseases in regenerative medicine. They are usually maintained with 10% fetal bovine serum (FBS in vitro. Modified platelet-rich plasma (mPRP would be a safe alternative to 10% FBS during SHEDs culture. Therefore, our study aimed to compare the proliferation and differentiation of SHEDs cultured in mPRP and FBS medium to explore an optimal concentration of mPRP for SHEDs maintenance. Platelets were harvested by automatic blood cell analyzer and activated by repeated liquid nitrogen freezing and thawing. The platelet-related cytokines were examined and analyzed by ELISA. SHEDs were extracted and cultured with different concentrations of mPRP or 10% FBS medium. Alkaline phosphatase (ALP activity was measured. Mineralization factors, RUNX2 and OCN, were measured by real-time PCR. SHEDs were characterized with mesenchymal stem cells (MSCs markers including vimentin, CD44, and CD105. mPRP at different concentrations (2, 5, 10, and 20% enhanced the growth of SHEDs. Moreover, mPRP significantly stimulated ALP activity and promoted expression of RUNX2 and OCN compared with 10% FBS. mPRP could efficiently facilitate proliferation and differentiation of SHEDs, and 2% mPRP would be an optimal substitute for 10% FBS during SHEDs expansion and differentiation in clinical scale manufacturing.

  9. The Underlying Social Dynamics of Paradigm Shifts.

    Science.gov (United States)

    Rodriguez-Sickert, Carlos; Cosmelli, Diego; Claro, Francisco; Fuentes, Miguel Angel

    2015-01-01

    We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution) within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i) marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm); and ii) radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology) that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm.

  10. The Underlying Social Dynamics of Paradigm Shifts.

    Directory of Open Access Journals (Sweden)

    Carlos Rodriguez-Sickert

    Full Text Available We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm; and ii radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm.

  11. Three paradigms of horror

    Directory of Open Access Journals (Sweden)

    Dejan Ognjanović

    2016-07-01

    Full Text Available Starting with the definition of horror as a literary genre the core story of which is based on a meeting with threatening Otherness whose influx into consensual reality and it’s tacit normality creates unrest and awakens fear in the protagonists and the audience, this paper defines the three key paradigms of the horror genre, based on the causes of fear, or rather the “monstrous” Otherness in them. Paradigm 1 concerns the “fear of one’s own self”: the root of the fear is inside, in the individual psyche, in the split, deceived, or in some other way unreliable self which is, consciously or unconsciously, harmful to others, and ultimately to itself. Paradigm 2 deals with the “Fear of others”: the root of fear is outside and is concerned with other people and other creatures which have an urge to occupy a certain human microcosm. Paradigm 3 is concerned with the “Fear of the numinous”: the root of the fear is mostly situated on the outside; however its shape is amorphous, ambivalent and unknowable. The “monster” is faceless; it touches on primary forces of the divine/demonic, and as such is situated on the very border between inside/outside. All three paradigms, with their main approaches and constitutive elements, are modulated through two basic possible treatments: the conservative and the progressive (liberal, which affords a total of six basic variations of horror. Starting from definitions given by John Carpenter, Robin Wood and his own, the author analyzes representative examples from horror literature and film for each paradigm and its variation, with a special accent on the image of Otherness and its connection to the norm, its intrusion into the status quo, anthropocentrism and the presence or absence of a happy ending. The paper demonstrates the richness of connotative potential within the horror genre and provides a basis for its taxonomy.

  12. Three paradigms of horror

    OpenAIRE

    Dejan Ognjanović

    2016-01-01

    Starting with the definition of horror as a literary genre the core story of which is based on a meeting with threatening Otherness whose influx into consensual reality and it’s tacit normality creates unrest and awakens fear in the protagonists and the audience, this paper defines the three key paradigms of the horror genre, based on the causes of fear, or rather the “monstrous” Otherness in them. Paradigm 1 concerns the “fear of one’s own self”: the root of the fear is inside, in the indivi...

  13. Evaluation of Not-Activated and Activated PRP in Hair Loss Treatment: Role of Growth Factor and Cytokine Concentrations Obtained by Different Collection Systems.

    Science.gov (United States)

    Gentile, Pietro; Cole, John P; Cole, Megan A; Garcovich, Simone; Bielli, Alessandra; Scioli, Maria Giovanna; Orlandi, Augusto; Insalaco, Chiara; Cervelli, Valerio

    2017-02-14

    Platelet rich plasma (PRP) was tested as a potential therapy for androgenetic alopecia (AGA) through two different clinical protocols in which one population (18 participants) received half-head treatment with autologous non-activated PRP (A-PRP) produced by CPunT Preparation System (Biomed Device, Modena, Italy) and the other half-head with placebo, and a second separated population in which all participants (n = 6, 3 participants per group) received treatment with calcium-activated PRP (AA-PRP) produced from one of two different PRP collection devices (Regen Blood Cell Therapy or Arthrex Angel System). For the A-PRP study, three treatments were administered over 30-day intervals. Trichoscan analysis of patients, three months post-treatment, showed a clinical improvement in the number of hairs in the target area (36 ± 3 hairs) and in total hair density (65±  5 hair cm2), whereas negligible improvements in hair count (1.1±  1.4 hairs) and density (1.9 ± 10.2 hair cm2) were seen in the region of the scalp that received placebo. Microscopic evaluation conducted two weeks after treatment showed also an increase in epidermal thickness, Ki67+ keratinocytes, and in the number of follicles. The AA-PRP treatment groups received a singular set of injections, and six months after the treatments were administered, notable differences in clinical outcomes were obtained from the two PRP collection devices (+90 ± 6 hair cm2 versus -73 ± 30 hair cm2 hair densities, Regen versus Arthrex). Growth factor concentrations in AA-PRP prepared from the two collection devices did not differ significantly upon calcium activation.

  14. Evaluation of Not-Activated and Activated PRP in Hair Loss Treatment: Role of Growth Factor and Cytokine Concentrations Obtained by Different Collection Systems

    Directory of Open Access Journals (Sweden)

    Pietro Gentile

    2017-02-01

    Full Text Available Platelet rich plasma (PRP was tested as a potential therapy for androgenetic alopecia (AGA through two different clinical protocols in which one population (18 participants received half-head treatment with autologous non-activated PRP (A-PRP produced by CPunT Preparation System (Biomed Device, Modena, Italy and the other half-head with placebo, and a second separated population in which all participants (n = 6, 3 participants per group received treatment with calcium-activated PRP (AA-PRP produced from one of two different PRP collection devices (Regen Blood Cell Therapy or Arthrex Angel System. For the A-PRP study, three treatments were administered over 30-day intervals. Trichoscan analysis of patients, three months post-treatment, showed a clinical improvement in the number of hairs in the target area (36 ± 3 hairs and in total hair density (65±  5 hair cm2, whereas negligible improvements in hair count (1.1±  1.4 hairs and density (1.9 ± 10.2 hair cm2 were seen in the region of the scalp that received placebo. Microscopic evaluation conducted two weeks after treatment showed also an increase in epidermal thickness, Ki67+ keratinocytes, and in the number of follicles. The AA-PRP treatment groups received a singular set of injections, and six months after the treatments were administered, notable differences in clinical outcomes were obtained from the two PRP collection devices (+90 ± 6 hair cm2 versus -73 ± 30 hair cm2 hair densities, Regen versus Arthrex. Growth factor concentrations in AA-PRP prepared from the two collection devices did not differ significantly upon calcium activation.

  15. A Randomized, Controlled Study of DTaP-IPV-HB-PRP-T, a Fully Liquid Hexavalent Vaccine, Administered in a 3-, 5- and 11- to 12-month Schedule.

    Science.gov (United States)

    Vesikari, Timo; Silfverdal, Sven-Arne; Jordanov, Emilia; Feroldi, Emmanuel

    2017-01-01

    To assess the immunogenicity and safety of a fully liquid, ready-to-use hexavalent DTaP-IPV-HB-PRP-T vaccine when administered in a 2 + 1 schedule at 3, 5 and 11-12 months of age. Phase III, randomized, active-controlled, observer-blind, multicenter study. Infants were randomized to receive DTaP-IPV-HB-PRP-T (N = 275) or a licensed control hexavalent vaccine (DTaP-IPV-HB//PRP~T: N = 275), both given in coadministration with Prevenar 13. Serum was analyzed for immune responses to all vaccine antigens. Noninferiority of DTaP-IPV-HB-PRP-T to the control vaccine was tested at completion of the primary series using predefined seroprotection (SP) rate and vaccine response (VR) rates. Safety was assessed using parental reports. Noninferiority of DTaP-IPV-HB-PRP-T to the control vaccine was demonstrated postdose 3 for each antigen, and the SP (for D, T, poliovirus 1, 2 and 3, hepatitis B and polyribosylribitol phosphate) and VR rates (for pertussis toxin and filamentous hemagglutinin) were high in each group. SP rates for D, T, polio 1, 2, 3 and VR rates for pertussis toxin and filamentous hemagglutinin were similar in each group. For hepatitis B, SP rate was slightly higher for DTaP-IPV-HB//PRP~T (99.6%) than DTaP-IPV-HB-PRP-T (96.4%), and for PRP, SP rate was higher for DTaP-IPV-HB-PRP-T (93.5%) than DTaP-IPV-HB//PRP~T (85.2%). For Prevenar 13, the SP rate was high for each serotype and similar for both groups. All vaccines were well tolerated. These study findings confirm the safety and immunogenicity and thus the suitability of this fully liquid hexavalent vaccine for administration in a 2 + 1 schedule.

  16. Trace elements as paradigms of developmental neurotoxicants

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Herz, Katherine T

    2015-01-01

    Trace elements have contributed unique insights into developmental neurotoxicity and serve as paradigms for such adverse effects. Many trace elements are retained in the body for long periods and can be easily measured to assess exposure by inexpensive analytical methods that became available...

  17. Microbicidal properties of Leukocyte- and Platelet-Rich Plasma/Fibrin (L-PRP/L-PRF): new perspectives.

    Science.gov (United States)

    Cieslik-Bielecka, A; Dohan Ehrenfest, D M; Lubkowska, A; Bielecki, T

    2012-01-01

    Platelets, as main actors of the first stage of the healing process, play an important role in tissue repair. Their granules contain many active substances, particularly over 30 growth factors with significant effects on the resident cells at the site of injury, such as mesenchymal stem cells, chondrocytes, fibroblasts, osteoblasts. This potential may be increased by the concentration of the platelets, using platelet-rich plasma/fibrin products. In the four families of platelet concentrates, 2 families contain also significant concentrations of leukocytes: L-PRP (Leukocyte- and Platelet-Rich Plasma) and L-PRF (Leukocyte- and Platelet-Rich Fibrin). Inductive properties of platelet concentrates were widely described. However, they present also antimicrobial effects. The antibacterial effects of L-PRP were highlighted in only a few in vitro studies. Strong activity comparable to gentamicin and oxacillin for L-PRP against methicillin susceptible Staphylococcus aureus (MSSA) was already demonstrated. L-PRP also inhibited the growth of methicillin resistant Staphylococcus aureus (MRSA) and Escherichia coli. Some authors also reported clinical observations about the reduction of infections and the induction of healing processes after the use of platelet concentrates in cardiac, orthopaedic, oral and maxillofacial surgery. However, very little is yet known about the antibacterial effects of these concentrates. In this manuscript, the current data about the antimicrobial agents and cells present in the platelet-rich plasma/fibrin are highlighted and discussed, in order to introduce this new key chapter of the platelet concentrate technology history.

  18. Ovine recombinant PrP as an inhibitor of ruminant prion propagation in vitro.

    Science.gov (United States)

    Workman, Rob G; Maddison, Ben C; Gough, Kevin C

    2017-07-04

    Prion diseases are fatal and incurable neurodegenerative diseases of humans and animals. Despite years of research, no therapeutic agents have been developed that can effectively manage or reverse disease progression. Recently it has been identified that recombinant prion proteins (rPrP) expressed in bacteria can act as inhibitors of prion replication within the in vitro prion replication system protein misfolding cyclic amplification (PMCA). Here, within PMCA reactions amplifying a range of ruminant prions including distinct Prnp genotypes/host species and distinct prion strains, recombinant ovine VRQ PrP displayed consistent inhibition of prion replication and produced IC50 values of 122 and 171 nM for ovine scrapie and bovine BSE replication, respectively. These findings illustrate the therapeutic potential of rPrPs with distinct TSE diseases.

  19. Paradigms in object recognition

    International Nuclear Information System (INIS)

    Mutihac, R.; Mutihac, R.C.

    1999-09-01

    A broad range of approaches has been proposed and applied for the complex and rather difficult task of object recognition that involves the determination of object characteristics and object classification into one of many a priori object types. Our paper revises briefly the three main different paradigms in pattern recognition, namely Bayesian statistics, neural networks, and expert systems. (author)

  20. Programming Language Paradigms

    Directory of Open Access Journals (Sweden)

    Bartoníček Jan

    2014-01-01

    Full Text Available This paper's goal is to briefly explain the basic theory behind programming languages and their history while taking a close look at different programming paradigms that are used today as well as describing their differences, benefits, and drawbacks

  1. Shifting the paradigm

    DEFF Research Database (Denmark)

    Kiss, Katalin; Brozik, Anna; Kucsma, Nora

    2012-01-01

    ABCB6, a member of the adenosine triphosphate-binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticuloc...... paradigm linking the expression and function of ABCB6 to mitochondria....

  2. Deconstructing Research: Paradigms Lost

    Science.gov (United States)

    Trifonas, Peter Pericles

    2009-01-01

    In recent decades, proponents of naturalistic and/or critical modes of inquiry advocating the use of ethnographic techniques for the narrative-based study of phenomena within pedagogical contexts have challenged the central methodological paradigm of educational research: that is, the tendency among its practitioners to adhere to quantitative…

  3. The Effect of Platelet-Rich Plasma (PRP on Improvement in Pain and Symptoms of Shoulder Subacromial Impingement Syndrome

    Directory of Open Access Journals (Sweden)

    Parisa Nejati

    2015-08-01

    Full Text Available Abstract Background: Subacromial impingement is one of the most common complaints of shoulder. Treatments include avoiding of painful activities, oral anti-pain drugs, physical therapy modalities, corticosteroid injection and exercise therapy. Some studies have shown that platelet- rich plasma(PRP is effective on tendinitis and tearing of tendons, ligaments and muscles, but evidence that has proved PRP as a conservative treatment in shoulder pathologies is very limited. This study aims to investigate the effect of PRP injection on relieving pain and improving daily function of patients with shoulder impingement syndrome. Materials and Methods: In this clinical trial study, patients older than 40 with pain more than three months were included. If they had three of four positive diagnostic clinical tests of shoulder impingement that were confirmed by shoulder MRI, could be injected PRP twice. The time between injections was 1 month. Pain was measured by visual analog scale (VAS and function was measured by two questionnaires named disabilities of the arm, shoulder and hand (DASH and western Ontario rotator cuff index (WORC. Range of motion (ROM of shoulder was measured in five directions by goniometry . All of these parameters were evaluated before intervention and in 1, 3, 6 months later. Results: with due attention to a six-month folloe-up, PRR injection was effective in pain reduction and improvement of patient's function (p<0.05. Shoulder Rom increased in all directions except external rotation and the power of shoulder muscles was evidently improved statistically in flexion, abduction and internal toration. Conclusion: PRP injection could effectively reduce pain and improve daily activities in patients with shoulder impingement syndrome.

  4. Adjunctive Platelet-Rich Plasma (PRP in Infrabony Regenerative Treatment: A Systematic Review and RCT’s Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Mubashir Saleem

    2018-01-01

    Full Text Available Background and Objective. The purpose of this study was to highlight the clinical performance of platelet-rich plasma (PRP used as an adjunctive tool for regeneration in infrabony periodontal defects using different biomaterials or performing different surgical flap approaches. Comparative evaluation of main clinical outcomes as probing pocket depth reduction, clinical attachment gain, and recession reduction with and without the use of PRP has been analysed. Materials and Methods. According to the focused question, an electronic and hand searching has been performed up to December 2016. From a batch of 73 articles, the selection strategy and Jadad quality assessment led us to include 15 studies for the meta-analysis. Results. Despite the high heterogeneity found and the lack of complete data regarding the selected clinical outcomes, a comparative analysis has been possible by the categorization of used biomaterials and surgical flap approaches. This method led us to observe the best performance of grafts with the use of adjunctive PRP in CAL gain and PPD reduction. No difference has been outlined with a specific surgical flap. Conclusions. Although PRP is considered a cheap and patient’s derived growth factor, the not conclusive data reported would suggest that its use in addition to bone substitutes could be of some clinical benefit in the regenerative treatment of infrabony defects. Clinical Relevance. This systematic review was intended to sort out the huge controversial debate in the field about the possible use of PRP in regenerative surgery in infrabony defect. The clinical relevance of using blood-borne growth factors to conventional procedures is effective as these could determine a better performance and outcomes despite the surgical approach adopted and limit the use of additional biomaterials for the blood clot stabilization.

  5. Comparison between Conventional Mechanical Fixation and Use of Autologous Platelet Rich Plasma (PRP) in Wound Beds Prior to Resurfacing with Split Thickness Skin Graft.

    Science.gov (United States)

    P Waiker, Veena; Shivalingappa, Shanthakumar

    2015-01-01

    Platelet rich plasma is known for its hemostatic, adhesive and healing properties in view of the multiple growth factors released from the platelets to the site of wound. The primary objective of this study was to use autologous platelet rich plasma (PRP) in wound beds for anchorage of skin grafts instead of conventional methods like sutures, staplers or glue. In a single center based randomized controlled prospective study of nine months duration, 200 patients with wounds were divided into two equal groups. Autologous PRP was applied on wound beds in PRP group and conventional methods like staples/sutures used to anchor the skin grafts in a control group. Instant graft adherence to wound bed was statistically significant in the PRP group. Time of first post-graft inspection was delayed, and hematoma, graft edema, discharge from graft site, frequency of dressings and duration of stay in plastic surgery unit were significantly less in the PRP group. Autologous PRP ensured instant skin graft adherence to wound bed in comparison to conventional methods of anchorage. Hence, we recommend the use of autologous PRP routinely on wounds prior to resurfacing to ensure the benefits of early healing.

  6. Autologous platelet-rich plasma (PRP) in chronic penile lichen sclerosus: the impact on tissue repair and patient quality of life.

    Science.gov (United States)

    Casabona, Francesco; Gambelli, Ilaria; Casabona, Federica; Santi, Pierluigi; Santori, Gregorio; Baldelli, Ilaria

    2017-04-01

    Lichen sclerosus (LS) is a chronic inflammatory skin condition that frequently involves the anogenital region. Ongoing research is focused on finding more effective treatments for tissue repair and reducing symptoms. The aim of this study is to evaluate the effectiveness of platelet-rich plasma (PRP) local injections in penile LS. Forty-five male patients affected by penile LS underwent injections of autologous PRP in the affected skin areas. Age at diagnosis and at first treatment, number of treatments, clinical conditions (phimosis, splitting, inflammation, synechiae, meatus stenosis), symptoms (pain, burning, itching), and functional impairment were considered. Treatment efficacy was also evaluated through the Investigator's Global Assessment (IGA) on a six-point Likert scale and the Dermatology Life Quality Index (DLQI). The patient age at LS diagnosis was 36.20 ± 9.19 years, while the mean age at the first PRP treatment was 42.96 ± 11.32 years (p PRP injections, it was observed in all patients a significant improvement in clinical conditions, with reduction/disappearance of symptoms. Topical steroid therapy, interrupted before PRP treatment, was not restarted by any patient. Only one patient underwent a later circumcision procedure. Both IGA scale and DLQI score showed a significant difference (p PRP treatment. PRP treatment in penile LS seems to be helpful to regenerate scarring, reduce symptoms, and improve patient quality of life. Further studies are necessary to evaluate long-term results.

  7. Small kinetochore associated protein (SKAP promotes UV-induced cell apoptosis through negatively regulating pre-mRNA processing factor 19 (Prp19.

    Directory of Open Access Journals (Sweden)

    Shan Lu

    Full Text Available Apoptosis is a regulated cellular suicide program that is critical for the development and maintenance of healthy tissues. Previous studies have shown that small kinetochore associated protein (SKAP cooperates with kinetochore and mitotic spindle proteins to regulate mitosis. However, the role of SKAP in apoptosis has not been investigated. We have identified a new interaction involving SKAP, and we propose a mechanism through which SKAP regulates cell apoptosis. Our experiments demonstrate that both overexpression and knockdown of SKAP sensitize cells to UV-induced apoptosis. Further study has revealed that SKAP interacts with Pre-mRNA processing Factor 19 (Prp19. We find that UV-induced apoptosis can be inhibited by ectopic expression of Prp19, whereas silencing Prp19 has the opposite effect. Additionally, SKAP negatively regulates the protein levels of Prp19, whereas Prp19 does not alter SKAP expression. Finally, rescue experiments demonstrate that the pro-apoptotic role of SKAP is executed through Prp19. Taken together, these findings suggest that SKAP promotes UV-induced cell apoptosis by negatively regulating the anti-apoptotic protein Prp19.

  8. A fully liquid DTaP-IPV-HB-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Turkish infants and toddlers

    Science.gov (United States)

    Ceyhan, Mehmet; Yıldırım, İnci; Tezer, Hasan; Devrim, İlker; Feroldi, Emmanuel

    2017-08-23

    Background/aim: Immunogenicity and safety of a primary series of a fully liquid, hexavalent DTaP-IPV-HB-PRP-T vaccine given at 2, 3, and 4 months of age compared to licensed comparators and a DTaP-IPV-HB-PRP-T booster at 15?18 months were evaluated. Materials and methods: This was a Phase III, randomized, open-label trial. Primary series (no hepatitis B [HB] at birth) of DTaP-IPV-HB-PRP-T (N = 155) (group 1) or licensed control vaccines (DTaP-IPV//PRP-T and standalone HB: N = 155) (group 2) and DTaP-IPV-HB-PRP-T booster were administered. Noninferiority was evaluated 1 month postprimary series for anti-HB seroprotection (SP). All other analyses were descriptive. Safety was assessed from parental reports. Results: Postprimary series noninferiority of anti-HB ≥ 10 mIU/mL was demonstrated for the DTaP-IPV-HB-PRP-T vaccine (94.0%) compared to the licensed control (96.1%). Postprimary series primary SP and seroconversion (SC) rates were high and similar for both groups. Antibody persistence (prebooster) was high for each antigen and similar between groups except for HB, which was lower for DTaP-IPV-HB-PRP-T than for standalone HB. For each antigen except HB, DTaP-IPV-HB-PRP-T booster responses were high and similar in each group. Safety was good for primary and booster series and similar between groups. Conclusion: The DTaP-IPV-HB-PRP-T vaccine is immunogenic and safe when administered in a challenging primary series schedule without HB vaccination at birth.

  9. The resilience of paradigm mixes

    DEFF Research Database (Denmark)

    Daugbjerg, Carsten; Farsund, Arild Aurvåg; Langhelle, Oluf

    2017-01-01

    This paper argues that a policy regime based on a paradigm mix may be resilient when challenged by changing power balances and new agendas. Controversies between the actors can be contained within the paradigm mix as it enables them to legitimize different ideational positions. Rather than engaging...... context changed. The paradigm mix proved sufficiently flexible to accommodate food security concerns and at the same time continue to take steps toward further liberalization. Indeed, the main players have not challenged the paradigm mix....

  10. CHANGE OF ENERGY PARADIGM

    Directory of Open Access Journals (Sweden)

    Ionut PURICA

    2013-05-01

    Full Text Available We are at the beginning of a change of paradigm in the energy systems of the whole World. Both new resources being found and exploited and the new technologies for energy conversion, transport and distribution, along with the associated artificial intelligence systems, are starting to create new futures, with different living values, for the greatest machine created by men: the energy system. Some relevant elements are presented in the paper along with the position and the perspectives of Romania.

  11. Dynamic Contacts of U2, RES, Cwc25, Prp8 and Prp45 Proteins with the Pre-mRNA Branch-Site and 3' Splice Site during Catalytic Activation and Step 1 Catalysis in Yeast Spliceosomes.

    Directory of Open Access Journals (Sweden)

    Cornelius Schneider

    Full Text Available Little is known about contacts in the spliceosome between proteins and intron nucleotides surrounding the pre-mRNA branch-site and their dynamics during splicing. We investigated protein-pre-mRNA interactions by UV-induced crosslinking of purified yeast B(act spliceosomes formed on site-specifically labeled pre-mRNA, and analyzed their changes after conversion to catalytically-activated B* and step 1 C complexes, using a purified splicing system. Contacts between nucleotides upstream and downstream of the branch-site and the U2 SF3a/b proteins Prp9, Prp11, Hsh49, Cus1 and Hsh155 were detected, demonstrating that these interactions are evolutionarily conserved. The RES proteins Pml1 and Bud13 were shown to contact the intron downstream of the branch-site. A comparison of the B(act crosslinking pattern versus that of B* and C complexes revealed that U2 and RES protein interactions with the intron are dynamic. Upon step 1 catalysis, Cwc25 contacts with the branch-site region, and enhanced crosslinks of Prp8 and Prp45 with nucleotides surrounding the branch-site were observed. Cwc25's step 1 promoting activity was not dependent on its interaction with pre-mRNA, indicating it acts via protein-protein interactions. These studies provide important insights into the spliceosome's protein-pre-mRNA network and reveal novel RNP remodeling events during the catalytic activation of the spliceosome and step 1 of splicing.

  12. Vascular access surveillance: case study of a false paradigm.

    Science.gov (United States)

    Paulson, William D; Moist, Louise; Lok, Charmaine E

    2013-01-01

    The hemodialysis vascular access surveillance controversy provides a case study of how enthusiasm for a new test or treatment can lead to adoption of a false paradigm. Paradigms are the beliefs and assumptions shared by those in a field of knowledge, and are commonly included in clinical practice guidelines. The guidelines of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommend that arteriovenous vascular accesses undergo routine surveillance for detection and correction of stenosis. This recommendation is based on the paradigm that surveillance of access blood flow or dialysis venous pressure combined with correction of stenosis improves access outcomes. However, the quality of evidence that supports this paradigm has been widely criticized. We tested the validity of the surveillance paradigm by applying World Health Organization (WHO) criteria for evaluating screening tests to a literature review of published vascular access studies. These criteria include four components: undesired condition, screening test, intervention, and desired outcome. The WHO criteria show that surveillance as currently practiced fails all four components and provides little or no significant benefit, suggesting that surveillance is a false paradigm. Once a paradigm is established, however, challenges to its validity are usually resisted even as new evidence indicates the paradigm is not valid. Thus, it is paramount to apply rigorous criteria when developing guidelines. Regulators may help promote needed changes in paradigms when cost and safety considerations coincide. © 2013 Wiley Periodicals, Inc.

  13. The peopleware paradigm.

    Science.gov (United States)

    Andrew, C G

    1996-08-01

    Manufacturing managements and practitioners alike are at long last realizing that the heartbeat of competitive advantage springs from peopleware, not hardware and software. But despite this heightened awareness the problem persists even among manufacturing professionals--they may talk a good game about priortizing people and quality, but all too many have precious little idea of how to go about it with constancy of purpose. This article bridges the gap and addresses the key issues in adopting the powerful new peopleware paradigm that provides the positive motivational climate for the improvement-change journey toward world-class performance through teamwork, innovation, and continuous improvement.

  14. Competitiveness: new economic paradigm?

    Directory of Open Access Journals (Sweden)

    Marlene Peñaloza

    2005-10-01

    Full Text Available Nowadays competitiveness is made up of “the new” paradigm that allows to prevail in the global World. Thus, it is inevitable to ask, was it required to be competitive to be successful in the international trade arena? Recognizing the discussion about it and its theoretical-conceptual density, the present paper studies this old notion whose meaning, in essence, is always the same one. This applies even though new realities in the present world-wide atmosphere confer to it a distinguishing character and new and old players are forced to organize actions and bring efforts together to obtain the competitive supremacy.

  15. Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice.

    Science.gov (United States)

    Eigenbrod, Sabina; Frick, Petra; Bertsch, Uwe; Mitteregger-Kretzschmar, Gerda; Mielke, Janina; Maringer, Marko; Piening, Niklas; Hepp, Alexander; Daude, Nathalie; Windl, Otto; Levin, Johannes; Giese, Armin; Sakthivelu, Vignesh; Tatzelt, Jörg; Kretzschmar, Hans; Westaway, David

    2017-01-01

    Prion diseases have been linked to impaired copper homeostasis and copper induced-oxidative damage to the brain. Divalent metal ions, such as Cu2+ and Zn2+, bind to cellular prion protein (PrPC) at octapeptide repeat (OR) and non-OR sites within the N-terminal half of the protein but information on the impact of such binding on conversion to the misfolded isoform often derives from studies using either OR and non-OR peptides or bacterially-expressed recombinant PrP. Here we created new transgenic mouse lines expressing PrP with disrupted copper binding sites within all four histidine-containing OR's (sites 1-4, H60G, H68G, H76G, H84G, "TetraH>G" allele) or at site 5 (composed of residues His-95 and His-110; "H95G" allele) and monitored the formation of misfolded PrP in vivo. Novel transgenic mice expressing PrP(TetraH>G) at levels comparable to wild-type (wt) controls were susceptible to mouse-adapted scrapie strain RML but showed significantly prolonged incubation times. In contrast, amino acid replacement at residue 95 accelerated disease progression in corresponding PrP(H95G) mice. Neuropathological lesions in terminally ill transgenic mice were similar to scrapie-infected wt controls, but less severe. The pattern of PrPSc deposition, however, was not synaptic as seen in wt animals, but instead dense globular plaque-like accumulations of PrPSc in TgPrP(TetraH>G) mice and diffuse PrPSc deposition in (TgPrP(H95G) mice), were observed throughout all brain sections. We conclude that OR and site 5 histidine substitutions have divergent phenotypic impacts and that cis interactions between the OR region and the site 5 region modulate pathogenic outcomes by affecting the PrP globular domain.

  16. Platelet-Rich Plasma (PRP) Rinses for the Treatment of Non-Responding Oral Lichen Planus: A Case Report

    OpenAIRE

    Elisabetta Merigo; Aldo Oppici; Anna Parlatore; Luigi Cella; Fabio Clini; Matteo Fontana; Carlo Fornaini

    2018-01-01

    Platelet-rich plasma (PRP) has been proposed for different applications in the medical field and in maxillofacial surgery thanks to its many growth factors, such as epidermal growth factor (EGF), fibroblast growth factor (FGF), and keratinocyte growth factor (KGF). Oral lichen planus (OLP) is a disease that affects the oral mucosa in a chronic way. This disease frequently worsens the quality of life of patients, particularly when clinical manifestations are of the erythematous or erosive/ulce...

  17. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Görmeli, Gökay; Görmeli, Cemile Ayşe; Ataoglu, Baybars; Çolak, Cemil; Aslantürk, Okan; Ertem, Kadir

    2017-03-01

    To compare the effectiveness of intraarticular (IA) multiple and single platelet-rich plasma (PRP) injections as well as hyaluronic acid (HA) injections in different stages of osteoarthritis (OA) of the knee. A total of 162 patients with different stages of knee OA were randomly divided into four groups receiving 3 IA doses of PRP, one dose of PRP, one dose of HA or a saline injection (control). Then, each group was subdivided into two groups: early OA (Kellgren-Lawrence grade 0 with cartilage degeneration or grade I-III) and advanced OA (Kellgren-Lawrence grade IV). The patients were evaluated before the injection and at the 6-month follow-ups using the EuroQol visual analogue scale (EQ-VAS) and International Knee Documentation Committee (IKDC) subjective scores. Adverse events and patient satisfaction were recorded. There was a statistically significant improvement in the IKDC and EQ-VAS scores in all the treatment groups compared with the control group. The knee scores of patients treated with three PRP injections were significantly better than those patients of the other groups. There was no significant difference in the scores of patients injected with one dose of PRP or HA. In the early OA subgroups, significantly better clinical results were achieved in the patients treated with three PRP injections, but there was no significant difference in the clinical results of patients with advanced OA among the treatment groups. The clinical results of this study suggest IA PRP and HA treatment for all stages of knee OA. For patients with early OA, multiple (3) PRP injections are useful in achieving better clinical results. For patients with advanced OA, multiple injections do not significantly improve the results of patients in any group. I.

  18. Platelet-rich plasma: why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration.

    Science.gov (United States)

    Filardo, G; Kon, E; Roffi, A; Di Matteo, B; Merli, M L; Marcacci, M

    2015-09-01

    The aim of this review was to analyze the available evidence on the clinical application of this biological approach for the injective treatment of cartilage lesions and joint degeneration, together with preclinical studies to support the rationale for the use of platelet concentrates, to shed some light and give indications on what to treat and what to expect from intra-articular injections of platelet-rich plasma (PRP). All in vitro, in vivo preclinical and clinical studies on PRP injective treatment in the English language concerning the effect of PRP on cartilage, synovial tissue, menisci, and mesenchymal stem cells were considered. A systematic review on the PubMed database was performed using the following words: (platelet-rich plasma or PRP or platelet concentrate or platelet lysate or platelet supernatant) and (cartilage or chondrocytes or synoviocytes or menisci or mesenchymal stem cells). Fifty-nine articles met the inclusion criteria: 26 were in vitro, 9 were in vivo, 2 were both in vivo and in vitro, and 22 were clinical studies. The analysis showed an increasing number of published studies over time. Preclinical evidence supports the use of PRP injections that might promote a favourable environment for joint tissues healing. Only a few high-quality clinical trials have been published, which showed a clinical improvement limited over time and mainly documented in younger patients not affected by advanced knee degeneration. Besides the limits and sometimes controversial findings, the preclinical literature shows an overall support toward this PRP application. An intra-articular injection does not just target cartilage; instead, PRP might influence the entire joint environment, leading to a short-term clinical improvement. Many biological variables might influence the clinical outcome and have to be studied to optimize PRP injective treatment of cartilage degeneration and osteoarthritis.

  19. A fully liquid DTaP-IPV-Hep B-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Mexican children.

    Science.gov (United States)

    Aquino, Amalia Guadalupe Becerra; Brito, Maricruz Gutiérrez; Doniz, Carlos E Aranza; Herrera, Juan Francisco Galán; Macias, Mercedes; Zambrano, Betzana; Plennevaux, Eric; Santos-Lima, Eduardo

    2012-10-05

    To evaluate an investigational, fully liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-Hep B-PRP-T: Hexaxim™) vaccine for primary and booster vaccination of healthy children in Mexico. Infants (N=1189) were randomized to receive one of three lots of the DTaP-IPV-Hep B-PRP-T vaccine or a licensed hexavalent control vaccine (Infanrix™ hexa) for primary vaccination at 2, 4 and 6 months. All participants who completed the primary series and agreed to participate in the booster part of the study received a dose of the investigational vaccine at 15-18 months of age. Validated serological assays and parental reports were used to assess immunogenicity and safety, respectively. Post-primary vaccination, ≥95.8% of participants in both the DTaP-IPV-Hep B-PRP-T and control groups were seroprotected (SP) against diphtheria, tetanus, poliovirus, hepatitis B and PRP, or had seroconverted (SC) to the pertussis toxin (PT) and filamentous hemagglutinin (FHA) pertussis antigens. The SP/SC rates induced by the three DTaP-IPV-Hep B-PRP-T lots were equivalent. No differences in SP/SC rates were observed between the pooled lots of investigational vaccine and the control vaccine. Antibody persistence at 15-18 months was comparable between groups, with strong increases in all antibody concentrations post-DTaP-IPV-Hep B-PRP-T booster. Both vaccines were well tolerated for primary vaccination, as was the booster dose of DTaP-IPV-Hep B-PRP-T. These study findings confirm the suitability of the combined, fully liquid DTaP-IPV-Hep B-PRP-T vaccine for inclusion in routine childhood vaccination schedules. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Evidence for a central role of PrP helix 2 in the nucleation of amyloid fibrils.

    Science.gov (United States)

    Honda, Ryo; Kuwata, Kazuo

    2018-02-01

    Amyloid fibrils are filamentous protein aggregates associated with the pathogenesis of a wide variety of human diseases. The formation of such aggregates typically follows nucleation-dependent kinetics, wherein the assembly and structural conversion of amyloidogenic proteins into oligomeric aggregates (nuclei) is the rate-limiting step of the overall reaction. In this study, we sought to gain structural insights into the oligomeric nuclei of the human prion protein (PrP) by preparing a series of deletion mutants lacking 14-44 of the C-terminal 107 residues of PrP and examined the kinetics and thermodynamics of these mutants in amyloid formation. An analysis of the experimental data using the concepts of the Φ-value analysis indicated that the helix 2 region (residues 168-196) acquires an amyloid-like β-sheet during nucleation, whereas the other regions preserves a relatively disordered structure in the nuclei. This finding suggests that the helix 2 region serves as the nucleation site for the assembly of amyloid fibrils.-Honda, R., Kuwata, K. Evidence for a central role of PrP helix 2 in the nucleation of amyloid fibrils.

  1. Behavior of Gingival Fibroblasts on Titanium Implant Surfaces in Combination with either Injectable-PRF or PRP

    Directory of Open Access Journals (Sweden)

    Xuzhu Wang

    2017-02-01

    Full Text Available Various strategies have been employed to speed tissue regeneration using bioactive molecules. Interestingly, platelet concentrates derived from a patient’s own blood have been utilized as a regenerative strategy in recent years. In the present study, a novel liquid platelet formulation prepared without the use of anti-coagulants (injectable-platelet-rich fibrin, i-PRF was compared to standard platelet-rich plasma (PRP with gingival fibroblasts cultured on smooth and roughened titanium implant surfaces. Standard PRP and i-PRF (centrifuged at 700 rpm (60× g for 3 min were compared by assays for fibroblast biocompatibility, migration, adhesion, proliferation, as well as expression of platelet-derived growth factor (PDGF, transforming growth factor-β (TGF-β, collagen1 (COL1 and fibronectin (FN. The results demonstrate that i-PRF induced significantly higher cell migration, as well as higher messenger RNA (mRNA levels of PDGF, TGF-β, collagen1 and fibronectin when compared to PRP. Furthermore, collagen1 synthesis was highest in the i-PRF group. These findings demonstrate that liquid platelet concentrates can be formulated without the use of anticoagulants and present much translational potential for future research. Future animal and clinical trials are now necessary to further investigate the potential of utilizing i-PRF for soft tissue regenerative protocols in combination with various biomaterials.

  2. The Effect of Autologous Activated Platelet Rich Plasma (AA-PRP Injection on Pattern Hair Loss: Clinical and Histomorphometric Evaluation

    Directory of Open Access Journals (Sweden)

    V. Cervelli

    2014-01-01

    Full Text Available To investigate the safety and clinical efficacy of AA-PRP injections for pattern hair loss. AA-PRP, prepared from a small volume of blood, was injected on half of the selected patients’ scalps with pattern hair loss. The other half was treated with placebo. Three treatments were given for each patient, with intervals of 1 month. The endpoints were hair re-growth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki-67 evaluation. At the end of the 3 cycles of treatment, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 18.0 hairs in the target area, and a mean increase in total hair density of 27.7 ( number of hairs/cm2 compared with baseline values. Microscopic evaluation showed the increase of epidermis thickness and of the number of hair follicles two weeks after the last AA-PRP treatment compared to baseline value (P<0.05. We also observed an increase of Ki67+ keratinocytes of epidermis and of hair follicular bulge cells and a slight increase of small blood vessels around hair follicles in the treated skin compared to baseline (P<0.05.

  3. Effect of Platelet-Rich Plasma (PRP versus Autologous Whole Blood on Pain and Function Improvement in Tennis Elbow: A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Seyed Ahmad Raeissadat

    2014-01-01

    Full Text Available Background. Autologous whole blood and platelet-rich plasma (PRP have been both suggested to treat chronic tennis elbow. The aim of the present study was to compare the effects of PRP versus autologous whole blood local injection in chronic tennis elbow. Methods. Forty patients with tennis elbow were randomly divided into 2 groups. Group 1 was treated with a single injection of 2 mL of autologous PRP and group 2 with 2 mL of autologous blood. Tennis elbow strap, stretching, and strengthening exercises were administered for both groups during a 2-month followup. Pain and functional improvements were assessed using visual analog scale (VAS, modified Mayo Clinic performance index for the elbow, and pressure pain threshold (PPT at 0, 4, and 8 weeks. Results. All pain and functional variables including VAS, PPT, and Mayo scores improved significantly in both groups 4 weeks after injection. No statistically significant difference was noted between groups regarding pain scores in 4-week follow-up examination (P>0.05. At 8-week reevaluations, VAS and Mayo scores improved only in PRP group (P<0.05. Conclusion. PRP and autologous whole blood injections are both effective to treat chronic lateral epicondylitis. PRP might be slightly superior in 8-week followup. However, further studies are suggested to get definite conclusion.

  4. Mutant PrP Suppresses Glutamatergic Neurotransmission in Cerebellar Granule Neurons by Impairing Membrane Delivery of VGCC α2δ-1 Subunit

    Science.gov (United States)

    Senatore, Assunta; Colleoni, Simona; Verderio, Claudia; Restelli, Elena; Morini, Raffaella; Condliffe, Steven B.; Bertani, Ilaria; Mantovani, Susanna; Canovi, Mara; Micotti, Edoardo; Forloni, Gianluigi; Dolphin, Annette C.; Matteoli, Michela; Gobbi, Marco; Chiesa, Roberto

    2012-01-01

    Summary How mutant prion protein (PrP) leads to neurological dysfunction in genetic prion diseases is unknown. Tg(PG14) mice synthesize a misfolded mutant PrP which is partially retained in the neuronal endoplasmic reticulum (ER). As these mice age, they develop ataxia and massive degeneration of cerebellar granule neurons (CGNs). Here, we report that motor behavioral deficits in Tg(PG14) mice emerge before neurodegeneration and are associated with defective glutamate exocytosis from granule neurons due to impaired calcium dynamics. We found that mutant PrP interacts with the voltage-gated calcium channel α2δ-1 subunit, which promotes the anterograde trafficking of the channel. Owing to ER retention of mutant PrP, α2δ-1 accumulates intracellularly, impairing delivery of the channel complex to the cell surface. Thus, mutant PrP disrupts cerebellar glutamatergic neurotransmission by reducing the number of functional channels in CGNs. These results link intracellular PrP retention to synaptic dysfunction, indicating new modalities of neurotoxicity and potential therapeutic strategies. PMID:22542184

  5. Platelet-rich plasma (PRP) and adipose-derived mesenchymal stem cells: stimulatory effects on proliferation and migration of fibroblasts and keratinocytes in vitro.

    Science.gov (United States)

    Stessuk, Talita; Puzzi, Maria Beatriz; Chaim, Elinton Adami; Alves, Paulo César Martins; de Paula, Erich Vinicius; Forte, Andresa; Izumizawa, Juliana Massae; Oliveira, Carolina Caliári; Frei, Fernando; Ribeiro-Paes, João Tadeu

    2016-09-01

    The clinical use of tissue engineering associated with cell therapy is considered a new alternative therapy for the repair of chronic lesions with potential application in different medical areas, mostly in orthopedic and dermatological diseases. Platelet-rich plasma (PRP) is a rich source of growth factors and cytokines important for wound healing. Adipose-derived mesenchymal stem cells (ADSCs) have shown potential to accelerate the resolution of ulcers, to stimulate cell proliferation, and to benefit the quality of skin repair. This study aims to determine the effect of PRP and conditioned medium (CM) from ADSC on fibroblast and keratinocyte proliferation in vitro. Migration and proliferation assays were performed to evaluate the growth of fibroblasts and keratinocytes in the presence of PRP, CM, and CM + PRP. Significant proliferative stimulation was observed after 48 h of culture (p PRP, 100 % CM, and 25 % PRP + 25 % CM, if compared with control. Keratinocyte proliferation was stimulated after 48 h in cultures with 25, 50, and 100 % CM, and growth was compared with controls. The migration assay detected a significant migratory stimulus in fibroblasts cultured with 10 % PRP + 10 % CM after 48 h. These in vitro results suggest that PRP and ADSC have therapeutic potential for healing and re-epithelialization of chronic wounds in vivo.

  6. Comparative assessment of prophylactic transfusions of platelet concentrates obtained by the PRP or buffy-coat methods, in patients undergoing allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Fernández-Muñoz, Hermógenes; Plaza, Eva M; Rivera-Caravaca, José Miguel; Candela, María José; Romera, Marta; De Arriba, Felipe; Lozano, María L; Vicente, Vicente; Heras, Inmaculada; Castilla-Llorente, Cristina; Rivera, José

    2018-03-27

    Whole blood-derived platelet concentrates can be obtained by the platelet-rich plasma (PRP-PCs) or the buffy-coat (BC-PCs) method. Few studies have shown that BC-PCs display lower in vitro platelet activation, but scarce information exists regarding transfusion efficacy. We have performed a retrospective study assessing platelet transfusion in patients undergoing allogeneic hematopoietic cell transplantation (AHCT) in our clinic, before and after the implementation of BC-PCs. We reviewed clinical records corresponding to 70 PRP-PCs and 86 BC-PCs prophylactic transfusions, which were performed to 55 AHCT patients. Transfusion efficacy was assessed by the 24-h post-transfusion corrected count increment (24-h CCI) and bleeding events. Clinical factors affecting transfusion outcome were also investigated. Clinical characteristics and the total number of platelet transfusions were similar among groups. Mean donor exposure was 5.8 and 5.0 in each single PRP-PCs and BC-PCs transfusion, respectively (p PRP-PCs (8.3[2.7-13.4] vs. 4.7[1.3-8.1]; p PRP-PCs transfusion (HR 4.54; 95% CI 1.72-12.01; p = 0.002). There were no differences between both groups regarding the bleeding events. In the AHCT setting, we hypothesize that BC-PCs transfusion, when compared to PRP-PCs, results in higher CCI and reduced donor exposure, but provides no significant benefit regarding bleeding outcome.

  7. Clinical-grade quality platelet-rich plasma releasate (PRP-R/SRGF) from CaCl2 -activated platelet concentrates promoted expansion of mesenchymal stromal cells.

    Science.gov (United States)

    Borghese, C; Agostini, F; Durante, C; Colombatti, A; Mazzucato, M; Aldinucci, D

    2016-08-01

    The aim of our study was to test a platelet-rich plasma releasate (PRP-R/SRGF) from CaCl2 -activated platelets as a source of growth factors for the expansion of mesenchymal stromal cells (MSCs). PRP-R/SRGF, obtained with a low-cost procedure, is characterized by a reduced variability of growth factor release. PRP-R/SRGF is a clinical-grade quality solution obtained from CaCl2 -activated platelets. Its activity was evaluated by measuring the proliferation, the phenotype, the differentiation potential and the immunosuppressive properties of MSCs derived from bone marrow (BM) and adipose tissue (AT). PRP-R/SRGF was more active than FBS to expand BM- and AT-derived MSCs. PRP-R/SRGF treatment did not affect the expression of typical MSCs surface markers, neither MSCs differentiation potential nor their capability to inhibit activated T-cell proliferation. The clinical-grade PRP-R/SRGF may be used in the clinical setting for the expansion of MSCs. © 2016 International Society of Blood Transfusion.

  8. Prion disease susceptibility is affected by β-structure folding propensity and local side-chain interactions in PrP

    Science.gov (United States)

    Khan, M. Qasim; Sweeting, Braden; Mulligan, Vikram Khipple; Arslan, Pharhad Eli; Cashman, Neil R.; Pai, Emil F.; Chakrabartty, Avijit

    2010-01-01

    Prion diseases occur when the normally α-helical prion protein (PrP) converts to a pathological β-structured state with prion infectivity (PrPSc). Exposure to PrPSc from other mammals can catalyze this conversion. Evidence from experimental and accidental transmission of prions suggests that mammals vary in their prion disease susceptibility: Hamsters and mice show relatively high susceptibility, whereas rabbits, horses, and dogs show low susceptibility. Using a novel approach to quantify conformational states of PrP by circular dichroism (CD), we find that prion susceptibility tracks with the intrinsic propensity of mammalian PrP to convert from the native, α-helical state to a cytotoxic β-structured state, which exists in a monomer–octamer equilibrium. It has been controversial whether β-structured monomers exist at acidic pH; sedimentation equilibrium and dual-wavelength CD evidence is presented for an equilibrium between a β-structured monomer and octamer in some acidic pH conditions. Our X-ray crystallographic structure of rabbit PrP has identified a key helix-capping motif implicated in the low prion disease susceptibility of rabbits. Removal of this capping motif increases the β-structure folding propensity of rabbit PrP to match that of PrP from mouse, a species more susceptible to prion disease. PMID:21041683

  9. Prion disease susceptibility is affected by beta-structure folding propensity and local side-chain interactions in PrP.

    Science.gov (United States)

    Khan, M Qasim; Sweeting, Braden; Mulligan, Vikram Khipple; Arslan, Pharhad Eli; Cashman, Neil R; Pai, Emil F; Chakrabartty, Avijit

    2010-11-16

    Prion diseases occur when the normally α-helical prion protein (PrP) converts to a pathological β-structured state with prion infectivity (PrP(Sc)). Exposure to PrP(Sc) from other mammals can catalyze this conversion. Evidence from experimental and accidental transmission of prions suggests that mammals vary in their prion disease susceptibility: Hamsters and mice show relatively high susceptibility, whereas rabbits, horses, and dogs show low susceptibility. Using a novel approach to quantify conformational states of PrP by circular dichroism (CD), we find that prion susceptibility tracks with the intrinsic propensity of mammalian PrP to convert from the native, α-helical state to a cytotoxic β-structured state, which exists in a monomer-octamer equilibrium. It has been controversial whether β-structured monomers exist at acidic pH; sedimentation equilibrium and dual-wavelength CD evidence is presented for an equilibrium between a β-structured monomer and octamer in some acidic pH conditions. Our X-ray crystallographic structure of rabbit PrP has identified a key helix-capping motif implicated in the low prion disease susceptibility of rabbits. Removal of this capping motif increases the β-structure folding propensity of rabbit PrP to match that of PrP from mouse, a species more susceptible to prion disease.

  10. Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study.

    Science.gov (United States)

    Togashi, Takehiro; Mitsuya, Nodoka; Kogawara, Osamu; Sumino, Shuji; Takanami, Yohei; Sugizaki, Kayoko

    2016-08-31

    Broad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013. We compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria-tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series. Long-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group - PRP-T group) was 3.7% (95% confidence interval: 0.099-7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (pvaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles. The immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns. Registered on ClinicalTrials.gov: NCT01379846. Copyright © 2016 The Authors

  11. The WIMP Paradigm: Current Status

    International Nuclear Information System (INIS)

    Feng, Jonathan

    2011-01-01

    The WIMP paradigm is the glue that joins together much of the high energy and cosmic frontiers. It postulates that most of the matter in the Universe is made of weakly-interacting massive particles, with implications for a broad range of experiments and observations. I will review the WIMP paradigm's underlying motivations, its current status in view of rapid experimental progress on several fronts, and recent theoretical variations on the WIMP paradigm theme.

  12. PARADIGM OF ACCOUNTING CHANGE

    Directory of Open Access Journals (Sweden)

    Constanta Iacob

    2016-12-01

    Full Text Available The words and phrases swop with each other and the apparent stability of a word’s meaning sometimes change in time. This explains why the generic term of accounting is used when referring to the qualities attributed to accounting,but also when it comes to organizing financial accounting function within the entity, and when referring concretely to keeping a double record with its specific means, methods and tools specific, respectively seen as a technical accounting.Speaking about the qualities of accounting, but also about the organizational form it takes, we note that there is a manifold meaning of the word accounting, which is why the purpose of this article is to demonstrate that the paradigm shift aimed at a new set of rules and if the rules changes, then we can change the very purpose of accounting.

  13. Paradigms for parasite conservation.

    Science.gov (United States)

    Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

    2016-08-01

    Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

  14. The folding mechanism and key metastable state identification of the PrP127-147 monomer studied by molecular dynamics simulations and Markov state model analysis.

    Science.gov (United States)

    Zhou, Shuangyan; Wang, Qianqian; Wang, Yuwei; Yao, Xiaojun; Han, Wei; Liu, Huanxiang

    2017-05-10

    The structural transition of prion proteins from a native α-helix (PrP C ) to a misfolded β-sheet-rich conformation (PrP Sc ) is believed to be the main cause of a number of prion diseases in humans and animals. Understanding the molecular basis of misfolding and aggregation of prion proteins will be valuable for unveiling the etiology of prion diseases. However, due to the limitation of conventional experimental techniques and the heterogeneous property of oligomers, little is known about the molecular architecture of misfolded PrP Sc and the mechanism of structural transition from PrP C to PrP Sc . The prion fragment 127-147 (PrP127-147) has been reported to be a critical region for PrP Sc formation in Gerstmann-Straussler-Scheinker (GSS) syndrome and thus has been used as a model for the study of prion aggregation. In the present study, we employ molecular dynamics (MD) simulation techniques to study the conformational change of this fragment that could be relevant to the PrP C -PrP Sc transition. Employing extensive replica exchange molecular dynamics (REMD) and conventional MD simulations, we sample a huge number of conformations of PrP127-147. Using the Markov state model (MSM), we identify the metastable conformational states of this fragment and the kinetic network of transitions between the states. The resulting MSM reveals that disordered random-coiled conformations are the dominant structures. A key metastable folded state with typical extended β-sheet structures is identified with Pro137 being located in a turn region, consistent with a previous experimental report. Conformational analysis reveals that intrapeptide hydrophobic interaction and two key residue interactions, including Arg136-His140 and Pro137-His140, contribute a lot to the formation of ordered extended β-sheet states. However, network pathway analysis from the most populated disordered state indicates that the formation of extended β-sheet states is quite slow (at the millisecond

  15. The α-helical C-terminal domain of full-length recombinant PrP converts to an in-register parallel β-sheet structure in PrP fibrils: evidence from solid state nuclear magnetic resonance.

    Science.gov (United States)

    Tycko, Robert; Savtchenko, Regina; Ostapchenko, Valeriy G; Makarava, Natallia; Baskakov, Ilia V

    2010-11-09

    We report the results of solid state nuclear magnetic resonance (NMR) measurements on amyloid fibrils formed by the full-length prion protein PrP (residues 23−231, Syrian hamster sequence). Measurements of intermolecular 13C−13C dipole−dipole couplings in selectively carbonyl-labeled samples indicate that β-sheets in these fibrils have an in-register parallel structure, as previously observed in amyloid fibrils associated with Alzheimer’s disease and type 2 diabetes and in yeast prion fibrils. Two-dimensional 13C−13C and 15N−13C solid state NMR spectra of a uniformly 15N- and 13C-labeled sample indicate that a relatively small fraction of the full sequence, localized to the C-terminal end, forms the structurally ordered, immobilized core. Although unique site-specific assignments of the solid state NMR signals cannot be obtained from these spectra, analysis with a Monte Carlo/simulated annealing algorithm suggests that the core is comprised primarily of residues in the 173−224 range. These results are consistent with earlier electron paramagnetic resonance studies of fibrils formed by residues 90−231 of the human PrP sequence, formed under somewhat different conditions [Cobb, N. J., Sonnichsen, F. D., McHaourab, H., and Surewicz, W. K. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 18946−18951], suggesting that an in-register parallel β-sheet structure formed by the C-terminal end may be a general feature of PrP fibrils prepared in vitro.

  16. Radiation a new paradigm... Societal impacts

    International Nuclear Information System (INIS)

    Sutcliffe, Jill

    2010-01-01

    Latency is associated with the time lag it takes for the health effects resulting from exposure to ionising radiation to show up. However, the term latency can also be applied to the time it takes for a policy to be implemented. This length of time has been suggested as broadly 40-year process. Given that radioactivity was identified and named in 1896, three paradigms are identified and examined from 1896 to 2016 and the criteria for a 4th paradigm suggested for the period 2017-2056. The review examines the changes that have taken place in scientific understanding and in public trust, a few key developments and the associated establishment of the related organisational infrastructure designed to collate and assess the evidence.

  17. In search of a consensus terminology in the field of platelet concentrates for surgical use: platelet-rich plasma (PRP), platelet-rich fibrin (PRF), fibrin gel polymerization and leukocytes.

    Science.gov (United States)

    Dohan Ehrenfest, David M; Bielecki, Tomasz; Mishra, Allan; Borzini, Piero; Inchingolo, Francesco; Sammartino, Gilberto; Rasmusson, Lars; Everts, Peter A

    2012-06-01

    In the field of platelet concentrates for surgical use, most products are termed Platelet-Rich Plasma (PRP). Unfortunately, this term is very general and incomplete, leading to many confusions in the scientific database. In this article, a panel of experts discusses this issue and proposes an accurate and simple terminology system for platelet concentrates for surgical use. Four main categories of products can be easily defined, depending on their leukocyte content and fibrin architecture: Pure Platelet-Rich Plasma (P-PRP), such as cell separator PRP, Vivostat PRF or Anitua's PRGF; Leukocyteand Platelet-Rich Plasma (L-PRP), such as Curasan, Regen, Plateltex, SmartPReP, PCCS, Magellan, Angel or GPS PRP; Pure Plaletet-Rich Fibrin (P-PRF), such as Fibrinet; and Leukocyte- and Platelet-Rich Fibrin (L-PRF), such as Choukroun's PRF. P-PRP and L-PRP refer to the unactivated liquid form of these products, their activated versions being respectively named P-PRP gels and L-PRP gels. The purpose of this search for a terminology consensus is to plead for a more serious characterization of these products. Researchers have to be aware of the complex nature of these living biomaterials, in order to avoid misunderstandings and erroneous conclusions. Understanding the biomaterials or believing in the magic of growth factors ? From this choice depends the future of the field.

  18. Integrity of Helix 2-Helix 3 Domain of the PrP Protein Is Not Mandatory for Prion Replication*

    Science.gov (United States)

    Salamat, Khalid; Moudjou, Mohammed; Chapuis, Jérôme; Herzog, Laetitia; Jaumain, Emilie; Béringue, Vincent; Rezaei, Human; Pastore, Annalisa; Laude, Hubert; Dron, Michel

    2012-01-01

    The process of prion conversion is not yet well understood at the molecular level. The regions critical for the conformational change of PrP remain mostly debated and the extent of sequence change acceptable for prion conversion is poorly documented. To achieve progress on these issues, we applied a reverse genetic approach using the Rov cell system. This allowed us to test the susceptibility of a number of insertion mutants to conversion into prion in the absence of wild-type PrP molecules. We were able to propagate several prions with 8 to 16 extra amino acids, including a polyglycine stretch and His or FLAG tags, inserted in the middle of the protease-resistant fragment. These results demonstrate the possibility to increase the length of the loop between helices H2 and H3 up to 4-fold, without preventing prion replication. They also indicate that this loop probably remains unstructured in PrPSc. We also showed that bona fide prions can be produced following insertion of octapeptides in the two C-terminal turns of H2. These insertions do not interfere with the overall fold of the H2-H3 domain indicating that the highly conserved sequence of the terminal part of H2 is not critical for the conversion. Altogether these data showed that the amplitude of modifications acceptable for prion conversion in the core of the globular domain of PrP is much greater than one might have assumed. These observations should help to refine structural models of PrPSc and elucidate the conformational changes underlying prions generation. PMID:22511770

  19. Integrity of helix 2-helix 3 domain of the PrP protein is not mandatory for prion replication.

    Science.gov (United States)

    Salamat, Khalid; Moudjou, Mohammed; Chapuis, Jérôme; Herzog, Laetitia; Jaumain, Emilie; Béringue, Vincent; Rezaei, Human; Pastore, Annalisa; Laude, Hubert; Dron, Michel

    2012-06-01

    The process of prion conversion is not yet well understood at the molecular level. The regions critical for the conformational change of PrP remain mostly debated and the extent of sequence change acceptable for prion conversion is poorly documented. To achieve progress on these issues, we applied a reverse genetic approach using the Rov cell system. This allowed us to test the susceptibility of a number of insertion mutants to conversion into prion in the absence of wild-type PrP molecules. We were able to propagate several prions with 8 to 16 extra amino acids, including a polyglycine stretch and His or FLAG tags, inserted in the middle of the protease-resistant fragment. These results demonstrate the possibility to increase the length of the loop between helices H2 and H3 up to 4-fold, without preventing prion replication. They also indicate that this loop probably remains unstructured in PrP(Sc). We also showed that bona fide prions can be produced following insertion of octapeptides in the two C-terminal turns of H2. These insertions do not interfere with the overall fold of the H2-H3 domain indicating that the highly conserved sequence of the terminal part of H2 is not critical for the conversion. Altogether these data showed that the amplitude of modifications acceptable for prion conversion in the core of the globular domain of PrP is much greater than one might have assumed. These observations should help to refine structural models of PrP(Sc) and elucidate the conformational changes underlying prions generation.

  20. PLATELET-RICH PLASMA (PRP AND ITS APPLICATION IN THE TREATMENT OF CHRONIC AND HARD-TO-HEAL SKIN WOUNDS. A Review.

    Directory of Open Access Journals (Sweden)

    Tsvetan Sokolov

    2015-12-01

    Full Text Available In the last few years various methods are being applied in the use of platelet-rich plasma (PRP during treatment in different orthopedic disease. They allow improvement of local biological condition and regeneration of different types of tissues. PRP is a modern treatment strategy with worldwide recognition. There is a high concentration of platelet growth factors in small amounts of plasma. PRP and its various forms have become one of the best methods to support the healing process of various tissues. PRP is used in regenerative medicine, because it provides two of three components (growth factors and scaffolds necessary for complete tissue regeneration. The particular reason for the appearance of lesions is important in order to select an appropriate treatment method and technical application. PRP may be used for treatment of various chronic and hard-to-heal cutaneous wounds, especially when standard conventional therapy is not good enough and surgical treatment is not possible. It reduces the duration, cost of treatment and the hospital stay. There is reduction of wound pain after starting the treatment, reduced risk of blood-borne disease transmission, wound healing is restored, and local immunity is activated.

  1. The Consumption Paradigm in Marketing

    Directory of Open Access Journals (Sweden)

    Eka Ardianto

    2003-08-01

    Full Text Available This article elaborates consumption paradigm in marketing. In background, this paper reviews different perspectives of consumption: economic perspective and marketing perspective. In ontology, this work describes various issues regarding consumption view. In epistemology, this article demonstrates how marketers especially researches explore the consumption phenomena. In methodology, the article describes experiential marketing –one of applied consumption paradigm in marketing, which could be an alternative choice of marketing practices.

  2. PrPST, a Soluble, Protease Resistant and Truncated PrP Form Features in the Pathogenesis of a Genetic Prion Disease

    Science.gov (United States)

    Frid, Kati; Binyamin, Orli; Gabizon, Ruth

    2013-01-01

    While the conversion of PrPC into PrPSc in the transmissible form of prion disease requires a preexisting PrPSc seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrPST), a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrPST as in TgMHu2ME199K mice, and “classical” PrPSc as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition. PMID:23922744

  3. PrP(ST), a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease.

    Science.gov (United States)

    Friedman-Levi, Yael; Mizrahi, Michal; Frid, Kati; Binyamin, Orli; Gabizon, Ruth

    2013-01-01

    While the conversion of PrP(C) into PrP(Sc) in the transmissible form of prion disease requires a preexisting PrP(Sc) seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrP(ST)), a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrP(ST) as in TgMHu2ME199K mice, and "classical" PrP(Sc) as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition.

  4. PrP(ST, a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease.

    Directory of Open Access Journals (Sweden)

    Yael Friedman-Levi

    Full Text Available While the conversion of PrP(C into PrP(Sc in the transmissible form of prion disease requires a preexisting PrP(Sc seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrP(ST, a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrP(ST as in TgMHu2ME199K mice, and "classical" PrP(Sc as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition.

  5. Recent Advances in Fractional Laser Resurfacing: New Paradigm in Optimal Parameters and Post-Treatment Wound Care

    Science.gov (United States)

    Hsiao, Francis C.; Bock, Gerald N.; Eisen, Daniel B.

    2012-01-01

    Background Laser plays an increasingly prominent role in skin rejuvenation. The advent of fractional photothermolysis revolutionizes its application. Microcolumns of skin are focally injured, leaving intervening normal skin to facilitate rapid wound healing and orderly tissue remodeling. The Problem Even with the popularity of fractional laser devices, we still have limited knowledge about the ideal treatment parameters and postlaser wound care. Basic/Clinical Science Advances Many clinicians believe that higher microbream energy in fractional laser devices results in better clinical outcome. Two recent studies argue against this assumption. One article demonstrates that lower fluence can induce comparable molecular changes with fewer side effects. Another study corroborates this by showing that lower-density settings produce similar clinical outcome in scar remodeling as higher-density ones, but with fewer side effects. To shed light on the optimal post-treatment wound care regimen from fractional ablative resurfacing, another paper shows that platelet-rich plasma (PRP) can reduce transepidermal water loss and skin color changes within 1 month after treatment. Clinical Care Relevance For fractional nonablative resurfacing, lower settings in fluence or density may produce similar dermal remodeling as higher settings and with a better side-effect profile. Moreover, autologous PRP appears to expedite wound healing after fractional ablative resurfacing. Conclusion Lower microbeam energy in fractional laser resurfacing produces similar molecular changes and clinical outcome with fewer side effects. The findings might portend a shift in the paradigm of treatment parameters. Autologous PRP can facilitate better wound healing, albeit modestly. Long-term follow-ups and larger studies are necessary to confirm these findings. PMID:24527307

  6. Paradigm Shifts in Ophthalmic Diagnostics.

    Science.gov (United States)

    Sebag, J; Sadun, Alfredo A; Pierce, Eric A

    2016-08-01

    Future advances in ophthalmology will see a paradigm shift in diagnostics from a focus on dysfunction and disease to better measures of psychophysical function and health. Practical methods to define genotypes will be increasingly important and non-invasive nanotechnologies are needed to detect molecular changes that predate histopathology. This is not a review nor meant to be comprehensive. Specific topics have been selected to illustrate the principles of important paradigm shifts that will influence the future of ophthalmic diagnostics. It is our impression that future evaluation of vision will go beyond visual acuity to assess ocular health in terms of psychophysical function. The definition of disease will incorporate genotype into what has historically been a phenotype-centric discipline. Non-invasive nanotechnologies will enable a paradigm shift from disease detection on a cellular level to a sub-cellular molecular level. Vision can be evaluated beyond visual acuity by measuring contrast sensitivity, color vision, and macular function, as these provide better insights into the impact of aging and disease. Distortions can be quantified and the psychophysical basis of vision can be better evaluated than in the past by designing tests that assess particular macular cell function(s). Advances in our understanding of the genetic basis of eye diseases will enable better characterization of ocular health and disease. Non-invasive nanotechnologies can assess molecular changes in the lens, vitreous, and macula that predate visible pathology. Oxygen metabolism and circulatory physiology are measurable indices of ocular health that can detect variations of physiology and early disease. This overview of paradigm shifts in ophthalmology suggests that the future will see significant improvements in ophthalmic diagnostics. The selected topics illustrate the principles of these paradigm shifts and should serve as a guide to further research and development. Indeed

  7. Gossamer superconductivity, new paradigm?

    Energy Technology Data Exchange (ETDEWEB)

    Won, Hyekyung [Department of Physics, Hallym University, Chuncheon 200-702 (Korea); Haas, Stephan; Parker, David [Department of Physics and Astronomy, University of Southern California, Los Angeles, CA 90089-0484 (United States); Maki, Kazumi [Department of Physics and Astronomy, University of Southern California, Los Angeles, CA 90089-0484 (United States); Max-Planck Institute for the Physics of Complex Systems, Noethnitzer Str. 38, 01187 Dresden (Germany); Dora, Balazs [Department of Physics, Budapest University of Technology and Economics, 1521 Budapest (Hungary); Virosztek, Attila [Department of Physics, Budapest University of Technology and Economics, 1521 Budapest (Hungary); Research Institute for Solid State Physics and Optics, P.O. Box 49, 1525 Budapest (Hungary)

    2006-01-01

    We review our recent works on d-wave density wave (dDW) and gossamer superconductivity (i.e. d-wave superconductivity in the presence of dDW) in high-T{sub c} cuprates and CeCoIn{sub 5}. a) We show that both the giant Nernst effect and the angle dependent magnetoresistance (ADMR) in the pseudogap phases of the cuprates and CeCoIn{sub 5} are manifestations of dDW. b) The phase diagram of high-T{sub c} cuprates is understood in terms of mean field theory, which includes two order parameters {delta}{sub 1} and {delta}{sub 2}, where one order paremeter is from dDW and the other from d-wave superconductivity. c) In the optimally to the overdoped region we find the spatially periodic dDW, an analogue of the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state, becomes more stable. d) In the underdoped region where {delta}{sub 2}/{delta}{sub 1}<<1 the Uemera relation is obtained within the present model. We speculate that the gossamer superconductivity is at the heart of high-T{sub c} cuprate superconductors, the heavy-fermion superconductor CeCoIn{sub 5} and the organic superconductors {kappa}-(ET){sub 2}Cu(NCS){sub 2} and (TMTSF){sub 2}PF{sub 6}. (copyright 2006 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  8. Evaluation of the effect of platelet rich plasma (PRP) on enhancement of bone healing in diaphyseal bone defects by radiography and computed tomography

    International Nuclear Information System (INIS)

    Özak, Ahmet; Yardimci, Cenk; Nİsbet, Özlem H.; Bayrak, İlkay Koray; Nİsbet, Cevat

    2010-01-01

    The effect of platelet-rich plasma (PRP) with autogenous cancellous bone graft on enhancement of bone healing in diaphyseal bone defects was evaluated. A 4-mm defect was created in the middiaphysis of the tibias of 20 rabbits. Rabbits were divided into two groups of ten animals each: only autogenous cancellous graft, PRP and autogenous cancellous graft. In animals of group 1, only autogenous cancellous grafts, and to those in group 2, PRP and autogenous cancellous grafts, were applied to the defect. Radiographical and computed tomography (CT) views were taken and evaluated on postoperative days 0, 15, 30, 60, and 90. According to the bone formation, union, and remodeling scores, group 1 had better scores than group 2 on days 30, 60, and 90. The density was significantly increased on day 60 than on days 0, 15, and 30 in group 1. In conclusion, it was evaluated that PRP could not enhance the bone regeneration in diaphyseal defects when used with autogenous cancellous bone graft

  9. Impact of strong selection for the PrP major gene on genetic variability of four French sheep breeds (Open Access publication

    Directory of Open Access Journals (Sweden)

    Pantano Thais

    2008-11-01

    Full Text Available Abstract Effective selection on the PrP gene has been implemented since October 2001 in all French sheep breeds. After four years, the ARR "resistant" allele frequency increased by about 35% in young males. The aim of this study was to evaluate the impact of this strong selection on genetic variability. It is focussed on four French sheep breeds and based on the comparison of two groups of 94 animals within each breed: the first group of animals was born before the selection began, and the second, 3–4 years later. Genetic variability was assessed using genealogical and molecular data (29 microsatellite markers. The expected loss of genetic variability on the PrP gene was confirmed. Moreover, among the five markers located in the PrP region, only the three closest ones were affected. The evolution of the number of alleles, heterozygote deficiency within population, expected heterozygosity and the Reynolds distances agreed with the criteria from pedigree and pointed out that neutral genetic variability was not much affected. This trend depended on breed, i.e. on their initial states (population size, PrP frequencies and on the selection strategies for improving scrapie resistance while carrying out selection for production traits.

  10. Amidation and structure relaxation abolish the neurotoxicity of the prion peptide PrP106-126 in vivo and in vitro

    DEFF Research Database (Denmark)

    Bergstrøm, Linda Alice; Hvass, Henriette Cordes; Zsurger, N.

    2005-01-01

    One of the major pathological hallmarks of transmissible spongiform encephalopathies (TSEs) is the accumulation of a pathogenic (scrapie) isoform (PrPSc) of the cellular prion protein (PrPC) primarily in the central nervous system. The synthetic prion peptide PrP106-126 shares many characteristics...

  11. Crystallization and preliminary X-ray diffraction analysis of the C-terminal domain of the human spliceosomal DExD/H-box protein hPrp22

    International Nuclear Information System (INIS)

    Kudlinzki, Denis; Nagel, Christian; Ficner, Ralf

    2009-01-01

    The cloning, purification and crystallization of the C-terminal domain of human hPrp22 are reported. This communication also contains data for the preliminary X-ray diffraction analysis. The Homo sapiens DExD/H-box protein hPrp22 is a crucial component of the eukaryotic pre-mRNA splicing machinery. Within the splicing cycle, it is involved in the ligation of exons and generation of the lariat and it additionally catalyzes the release of mature mRNA from the spliceosomal U5 snRNP. The yeast homologue of this protein, yPrp22, shows ATP-dependent RNA-helicase activity and is capable of unwinding RNA/RNA duplex molecules. A truncated construct coding for residues 950–1183 of human Prp22, comprising the structurally and functionally uncharacterized C-terminal domain, was cloned into an Escherichia coli expression vector. The protein was subsequently overproduced, purified and crystallized. The crystals obtained diffracted to 2.1 Å resolution, belonged to the tetragonal space group P4 1 2 1 2 or P4 3 2 1 2, with unit-cell parameters a = b = 78.2, c = 88.4 Å, and contained one molecule in the asymmetric unit

  12. PrP0\\0 mice show behavioral abnormalities that suggest PrPC has a role in maintaining the cytoskeleton.

    Science.gov (United States)

    Background/Introduction. PrPC is highly conserved among mammals, but its natural function is unclear. Prnp ablated mice (PrP0/0) appear to develop normally and are able to reproduce. These observations seem to indicate that the gene is not essential for viability, in spite of it being highly conse...

  13. The synthesis paradigm in genetics.

    Science.gov (United States)

    Rice, William R

    2014-02-01

    Experimental genetics with model organisms and mathematically explicit genetic theory are generally considered to be the major paradigms by which progress in genetics is achieved. Here I argue that this view is incomplete and that pivotal advances in genetics--and other fields of biology--are also made by synthesizing disparate threads of extant information rather than generating new information from experiments or formal theory. Because of the explosive expansion of information in numerous "-omics" data banks, and the fragmentation of genetics into numerous subdisciplines, the importance of the synthesis paradigm will likely expand with time.

  14. Transmission pricing: paradigms and methodologies

    Energy Technology Data Exchange (ETDEWEB)

    Shirmohammadi, Dariush [Pacific Gas and Electric Co., San Francisco, CA (United States); Vieira Filho, Xisto; Gorenstin, Boris [Centro de Pesquisas de Energia Eletrica (CEPEL), Rio de Janeiro, RJ (Brazil); Pereira, Mario V.P. [Power System Research, Rio de Janeiro, RJ (Brazil)

    1994-12-31

    In this paper we describe the principles of several paradigms and methodologies for pricing transmission services. The paper outlines some of the main characteristics of these paradigms and methodologies such as where they may be used for best results. Due to their popularity, power flow based MW-mile and short run marginal cost pricing methodologies will be covered in some detail. We conclude the paper with examples of the application of these two pricing methodologies for pricing transmission services in Brazil. (author) 25 refs., 2 tabs.

  15. CNN a paradigm for complexity

    CERN Document Server

    Chua, Leon O

    1998-01-01

    Revolutionary and original, this treatise presents a new paradigm of EMERGENCE and COMPLEXITY, with applications drawn from numerous disciplines, including artificial life, biology, chemistry, computation, physics, image processing, information science, etc.CNN is an acronym for Cellular Neural Networks when used in the context of brain science, or Cellular Nonlinear Networks, when used in the context of emergence and complexity. A CNN is modeled by cells and interactions: cells are defined as dynamical systems and interactions are defined via coupling laws. The CNN paradigm is a universal Tur

  16. Robust nonlinear PID-like fuzzy logic control of a planar parallel (2PRP-PPR) manipulator.

    Science.gov (United States)

    Londhe, P S; Singh, Yogesh; Santhakumar, M; Patre, B M; Waghmare, L M

    2016-07-01

    In this paper, a robust nonlinear proportional-integral-derivative (PID)-like fuzzy control scheme is presented and applied to complex trajectory tracking control of a 2PRP-PPR (P-prismatic, R-revolute) planar parallel manipulator (motion platform) with three degrees-of-freedom (DOF) in the presence of parameter uncertainties and external disturbances. The proposed control law consists of mainly two parts: first part uses a feed forward term to enhance the control activity and estimated perturbed term to compensate for the unknown effects namely external disturbances and unmodeled dynamics, and the second part uses a PID-like fuzzy logic control as a feedback portion to enhance the overall closed-loop stability of the system. Experimental results are presented to show the effectiveness of the proposed control scheme. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

  17. Is Platelet-Rich Plasma (PRP) Effective in the Treatment of Acute Muscle Injuries? A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Grassi, Alberto; Napoli, Francesca; Romandini, Iacopo; Samuelsson, Kristian; Zaffagnini, Stefano; Candrian, Christian; Filardo, Giuseppe

    2018-04-01

    Muscle lesions account for one-third of sport-related injuries, thus representing a substantial problem for both players and their teams. The use of platelet-rich plasma (PRP) injections is rapidly growing in clinical practice, prompted by an unmet clinical need with a large commercial market. However, after early reports of positive preliminary experience, higher quality studies recently questioned the real benefit provided by PRP injections to promote muscle healing and return to sport. To evaluate the effect of platelet-rich plasma (PRP) injections on outcomes following acute muscle injuries. Meta-analysis of randomized, controlled trials (RCTs), Level I. PubMed (MEDLINE), Cochrane (CENTRAL), Web of Science, clinicaltrials.gov, who.int, isrctn.com, greylit.org, opengrey.eu. RCTs investigating the effect of PRP for the treatment of acute muscle injuries against at least one control group including patients treated with placebo injection or physical therapy. The outcomes evaluated were time to return to sport, re-injuries, complications, pain, muscle strength, range of motion (ROM)/flexibility, muscle function, and imaging. Six studies, involving 374 patients, were included in the meta-analysis. The time to return to sport evaluated in all six studies was significantly shorter in patients treated with PRP (mean difference = - 7.17 days). However, if only the double-blind studies (n = 2) or studies including only hamstring injuries (n = 3) were considered, non-significant differences were found. Re-injuries (relative risk = - 0.03) and complications (relative risk = 0.01) were also similar between the two groups (p > 0.05), nor were any substantial differences found regarding pain, muscle strength, ROM/flexibility, muscle function, and imaging. The performance bias was high risk due to the lack of patient blinding in four studies. The quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was

  18. PrP expression, PrPSc accumulation and innervation of splenic compartments in sheep experimentally infected with scrapie.

    Directory of Open Access Journals (Sweden)

    Randi Sørby

    Full Text Available BACKGROUND: In prion disease, the peripheral expression of PrP(C is necessary for the transfer of infectivity to the central nervous system. The spleen is involved in neuroinvasion and neural dissemination in prion diseases but the nature of this involvement is not known. The present study undertook the investigation of the spatial relationship between sites of PrP(Sc accumulation, localisation of nerve fibres and PrP(C expression in the tissue compartments of the spleen of scrapie-inoculated and control sheep. METHODOLOGY/PRINCIPAL FINDINGS: Laser microdissection and quantitative PCR were used to determine PrP mRNA levels and results were compared with immunohistochemical protocols to distinguish PrP(C and PrP(Sc in tissue compartments of the spleen. In sheep experimentally infected with scrapie, the major sites of accumulation of PrP(Sc in the spleen, namely the lymphoid nodules and the marginal zone, expressed low levels of PrP mRNA. Double immunohistochemical labelling for PrP(Sc and the pan-nerve fibre marker, PGP, was used to evaluate the density of innervation of splenic tissue compartments and the intimacy of association between PrP(Sc and nerves. Some nerve fibres were observed to accompany blood vessels into the PrP(Sc-laden germinal centres. However, the close association between nerves and PrP(Sc was most apparent in the marginal zone. Other sites of close association were adjacent to the wall of the central artery of PALS and the outer rim of germinal centres. CONCLUSIONS/SIGNIFICANCE: The findings suggest that the degree of PrP(Sc accumulation does not depend on the expression level of PrP(C. Though several splenic compartments may contribute to neuroinvasion, the marginal zone may play a central role in being the compartment with most apparent association between nerves and PrP(Sc.

  19. Familial CJD Associated PrP Mutants within Transmembrane Region Induced Ctm-PrP Retention in ER and Triggered Apoptosis by ER Stress in SH-SY5Y Cells

    Science.gov (United States)

    Wang, Xin; Shi, Qi; Xu, Kun; Gao, Chen; Chen, Cao; Li, Xiao-Li; Wang, Gui-Rong; Tian, Chan; Han, Jun; Dong, Xiao-Ping

    2011-01-01

    Background Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP) gene that are presumed to favor conversion of the cellular isoform of PrP (PrPC) to the pathogenic one (PrPSc). The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K) into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. Methodology/Principal Findings To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER), the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL) and PrP with three amino acids exchange in transmembrane region (PrP-3AV) were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP) were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and capase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V) induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K) failed. Conclusions/Significance The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them the mutants

  20. Familial CJD associated PrP mutants within transmembrane region induced Ctm-PrP retention in ER and triggered apoptosis by ER stress in SH-SY5Y cells.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available BACKGROUND: Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP gene that are presumed to favor conversion of the cellular isoform of PrP (PrP(C to the pathogenic one (PrP(Sc. The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. METHODOLOGY/PRINCIPAL FINDINGS: To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER, the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL and PrP with three amino acids exchange in transmembrane region (PrP-3AV were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and caspase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K failed. CONCLUSIONS/SIGNIFICANCE: The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them

  1. Superior integrin activating capacity and higher adhesion to fibrinogen matrix in buffy coat-derived platelet concentrates (PCs) compared to PRP-PCs.

    Science.gov (United States)

    Beshkar, Pezhman; Hosseini, Ehteramolsadat; Ghasemzadeh, Mehran

    2018-02-01

    Regardless of different sources, methods or devices which are applied for preparation of therapeutic platelets, these products are generally isolated from whole blood by the sedimentation techniques which are based on PRP or buffy coat (BC) separation. As a general fact, platelet preparation and storage are also associated with some deleterious changes that known as platelet storage lesion (PSL). Although these alternations in platelet functional activity are aggravated during storage, whether technical issues within preparation can affect integrin activation and platelet adhesion to fibrinogen were investigated in this study. PRP- and BC-platelet concentrates (PCs) were subjected to flowcytometry analysis to examine the expression of platelet activation marker, P-selectin as well as active confirmation of the GPIIb/IIIa (α IIb β 3 ) on day 0, 1, 3 and 5 post-storage. Platelet adhesion to fibrinogen matrix was evaluated by fluorescence microscopy. Glucose concentration and LDH activity were also measured by colorimetric methods. The increasing P-selectin expression during storage was in a reverse correlation with PAC-1 binding (r = -0.67; p = .001). PRP-PCs showed the higher level of P-selectin expression than BC-PCs, whereas the levels of PAC-1 binding and platelet adhesion to fibrinogen matrix were significantly lower in PRP-PCs. Higher levels of active confirmation of the GPIIb/IIIa in BC-PCs were also associated with greater concentration of glucose in these products. We demonstrated the superior capacities of integrin activation and adhesion to fibrinogen for BC-PCs compared to those of PRP-PCs. These findings may provide more advantages for BC method of platelet preparation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Functional assessment of autologous platelet-rich plasma (PRP) after long-term storage at -20 °C without any preservation agent.

    Science.gov (United States)

    Hosnuter, Mubin; Aslan, Cem; Isik, Daghan; Caliskan, Gorkem; Arslan, Banu; Durgun, Mustafa

    2017-08-01

    Platelet-rich plasma (PRP) is increasingly being used in the treatment of chronic wounds, pathologies of the musculoskeletal system, and in cosmetic medicine; however, the preparation of platelet-rich plasma is both time-consuming and requires invasive intervention. Additional costs are introduced if special equipment is used during preparation. The aim of the present study is to test whether autologous platelet-rich plasma (PRP) preserves the feature of growth factor release when stored at -20 °C after preparation. Autologous PRP concentrates were prepared using whole blood samples obtained from 20 healthy subjects and divided into three parts to form three groups. Epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet derived growth factor-AB (PDGF-AB), insulin-like growth factor 1 (IGF-1), transforming growth factor-beta (TGF-β), and P-Selectin levels were immediately analysed in the control group. The other groups were defined as the experimental groups and were stored at -20 °C and analysed on the 7th and the 14th days. The same growth factors were tested in the experimental groups. The growth factors (EGF, VEGF, PDGF-AB, IGF-1, TGF-β) and P-selectin levels were significantly decreased in the autologous PRP samples stored at -20 °C compared to the control group. The growth factor levels on days 7 and 14 suggest that autologous PRP can be stored at -20 °C without preservative agents, although in vivo studies are required in order to evaluate the clinical efficacy of the detected growth factor levels.

  3. Quantification of platelets and platelet derived growth factors from platelet-rich-plasma (PRP) prepared at different centrifugal force (g) and time.

    Science.gov (United States)

    Arora, Satyam; Doda, Veena; Kotwal, Urvershi; Dogra, Mitu

    2016-02-01

    Platelet derived biomaterials represent a key source of cytokines and growth factors extensively used for tissue regeneration; wound healing and tissue repair. Our study was to quantify platelets and growth factors released by PRP when prepared at different centrifugal force (g) and time. Our study was approved by the institutional ethical committee. One hundred millilitres of whole blood (WB) was collected in bag with CPDA as the anticoagulant(AC); (14 mL for 100 mL WB ratio). Nine aliquots of 10 mL each were made from the bag and set of three aliquots were made a group. PRP was prepared at varying centrifugal force (group A: -110 g, group B: -208 g & group C: -440 g) & time (1: -5 min, 2: -10 min & 3: -20 min). Contents of each PRP prepared were analysed. Commercial sandwich ELISA kits were used to quantify the concentrations of CD62P (Diaclone SAS; France), Platelet derived growth factors-AB (Qayee-Bio; China), transforming growth factor-β1 (DRG; Germany) and vascular endothelial growth factor (Boster Immuno Leader; USA) released in each PRP prepared. Eight volunteers were enrolled in the study (24-30 years). The baseline blood counts of all the volunteers were comparable (p ≥ 0.05). Mean ± SD of platelet yield of all nine groups ranged from 17.2 ± 4.2% to 78.7 ± 5.7%. Each PRP was activated with calcified thromboplastin to quantify the growth factors released by them. Significantly higher (p < 0.05) transforming growth factor-β1 and vascular endothelial growth factor were released compared to the baseline. Our study highlights the variation in both force (g) and time results in changes at cellular level and growth factor concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Programming Language: Concepts and Paradigms

    OpenAIRE

    Ruiz Lizama, Edgar

    2014-01-01

    The article presents the concepts that govern around the programming languages and the paradigms of the programming and the influence in the development of the software. El artículo presenta los conceptos que rigen a los lenguajes de programación y los paradigmas de la programación y como estos influyen en el desarrollo del software.

  5. Understanding the land management paradigm

    DEFF Research Database (Denmark)

    Enemark, Stig

    2006-01-01

    There is a worldwide need to build understanding of the land management paradigm and for institutional development to establish sustainable national concepts. This includes creation and adoption of a policy on land development, and an approach that combines the land administration...

  6. Artificial life, the new paradigm

    International Nuclear Information System (INIS)

    Martinez Paez, Jose Jesus

    1998-01-01

    A chronological synthesis of the most important facts is presented in the theoretical development and computational simulation that they have taken to the formation of a new paradigm that is known as artificial life; their characteristics and their main investigation lines are analyzed. Finally, a description of its work is made in the National University of Colombia

  7. Combined use of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and platelet rich plasma (PRP) stimulates proliferation and differentiation of myoblasts in vitro: new therapeutic perspectives for skeletal muscle repair/regeneration.

    Science.gov (United States)

    Sassoli, Chiara; Vallone, Larissa; Tani, Alessia; Chellini, Flaminia; Nosi, Daniele; Zecchi-Orlandini, Sandra

    2018-02-05

    Satellite cell-mediated skeletal muscle repair/regeneration is compromised in cases of extended damage. Bone marrow mesenchymal stromal cells (BM-MSCs) hold promise for muscle healing but some criticisms hamper their clinical application, including the need to avoid animal serum contamination for expansion and the scarce survival after transplant. In this context, platelet-rich plasma (PRP) could offer advantages. Here, we compare the effects of PRP or standard culture media on C2C12 myoblast, satellite cell and BM-MSC viability, survival, proliferation and myogenic differentiation and evaluate PRP/BM-MSC combination effects in promoting myogenic differentiation. PRP induced an increase of mitochondrial activity and Ki67 expression comparable or even greater than that elicited by standard media and promoted AKT signaling activation in myoblasts and BM-MSCs and Notch-1 pathway activation in BM-MSCs. It stimulated MyoD, myogenin, α-sarcomeric actin and MMP-2 expression in myoblasts and satellite cell activation. Notably, PRP/BM-MSC combination was more effective than PRP alone. We found that BM-MSCs influenced myoblast responses through a paracrine activation of AKT signaling, contributing to shed light on BM-MSC action mechanisms. Our results suggest that PRP represents a good serum substitute for BM-MSC manipulation in vitro and could be beneficial towards transplanted cells in vivo. Moreover, it might influence muscle resident progenitors' fate, thus favoring the endogenous repair/regeneration mechanisms. Finally, within the limitations of an in vitro experimentation, this study provides an experimental background for considering the PRP/BM-MSC combination as a potential therapeutic tool for skeletal muscle damage, combining the beneficial effects of BM-MSCs and PRP on muscle tissue, while potentiating BM-MSC functionality.

  8. RENEGOTIATION MINING CONTRACT: LEGAL PARADIGM RECONSTRUCTION EFFORTS

    Directory of Open Access Journals (Sweden)

    Marilang -

    2014-07-01

    Full Text Available Renegotiation contract mining is not a priori notion that was born but is driven by the fact that empirical Work Contract (KK and coal mining concessions of the Works Agreement (Cca that are valid for this resulted in profits which are not comparable between countries with investors (domestic and foreign. In addition, Law No. 4 of 2009 about Mineral and Coal Mining (minerba through article 169 have been injected that though the mining contracts during the validity of this, still respected until the end, however, if the implementation of these contracts give rise to distortions for the national interest, then the Government must encourage the investors to do Renegotiation against existing contracts to comply with legislation minerba forever within a period of one year since the enactment of the legislation this minerba. Renegotiation mining contracts that have been approved on the fact of the matter is simply an attempt to reconstruct the ruling paradigm, so with that paradigm shift, both parties can reach the intersection for the benefit of both parties, i.e. the parties proportionately Indonesia suffered no losses on the one hand, and the benefit of the domestic and foreign investors remain in reasonable limits on the other. 

  9. Changing environments or shifting paradigms? Strategic decision making toward water protection in Helsinki, 1850-2000.

    Science.gov (United States)

    Laakkonen, Simo; Laurila, Sari

    2007-04-01

    The study examines the history of strategic decision-making concerning water protection in Helsinki, 1850-2000. We identified five major strategic decisions that occurred during the study period. The results indicate that strategic decision-making evolves in long-term policy cycles that last on average 20-30 years. New policy cycles are caused by paradigm shifts. Paradigms are shared and predominant ways of understanding reality that help when groups must act to solve common and complex environmental problems. However the internal structure and external dynamics of paradigms are contradictory. Although paradigms serve initially as means to redefine problems and find creative solutions, as time goes by each paradigm seems to become also a barrier that restricts the introduction of new ways of thinking and acting. The power of paradigms lies in the fact that they can be defined as scientific but also social, political, or cultural agreements depending on the context.

  10. Policy paradigms, transnationalism, and domestic politics

    National Research Council Canada - National Science Library

    Skogstad, Grace Darlene

    2011-01-01

    Policy Paradigms, Transnationalism, and Domestic Politics offers a variety of perspectives on the development of policy paradigms -- the ideas that structure thinking about what can and should be done in a policy domain...

  11. Is the psychological refractory period effect for ideomotor compatible tasks eliminated by speed-stress instructions?

    Science.gov (United States)

    Shin, Yun Kyoung; Cho, Yang Seok; Lien, Mei-Ching; Proctor, Robert W

    2007-09-01

    It has been argued that the psychological refractory period (PRP) effect is eliminated with two ideomotor compatible tasks when instructions stress fast and simultaneous responding. Three experiments were conducted to test this hypothesis. In all experiments, Task 1 required spatially compatible manual responses (left or right) to the direction of an arrow, and Task 2 required saying the name of the auditory letter A or B. In Experiments 1 and 3, the manual responses were keypresses made with the left and right hands, whereas in Experiment 2 they were left-right toggle-switch movements made with the dominant hand. Instructions that stressed response speed reduced reaction time and increased error rate compared to standard instructions to respond fast and accurately, but did not eliminate the PRP effect on Task 2 reaction time. These results imply that, even when response speed is emphasized, ideomotor compatible tasks do not bypass response selection.

  12. Black hole evaporation: a paradigm

    International Nuclear Information System (INIS)

    Ashtekar, Abhay; Bojowald, Martin

    2005-01-01

    A paradigm describing black hole evaporation in non-perturbative quantum gravity is developed by combining two sets of detailed results: (i) resolution of the Schwarzschild singularity using quantum geometry methods and (ii) time evolution of black holes in the trapping and dynamical horizon frameworks. Quantum geometry effects introduce a major modification in the traditional spacetime diagram of black hole evaporation, providing a possible mechanism for recovery of information that is classically lost in the process of black hole formation. The paradigm is developed directly in the Lorentzian regime and necessary conditions for its viability are discussed. If these conditions are met, much of the tension between expectations based on spacetime geometry and structure of quantum theory would be resolved

  13. Three Paradigms of Social Assistance

    Directory of Open Access Journals (Sweden)

    Pierre-Marc Daigneault

    2014-11-01

    Full Text Available “Ideas,” which are defined as the normative and cognitive beliefs of actors, are fundamental to a full understanding of the welfare state and, in particular, of social assistance. However, policy ideas have been neglected in most typologies of social assistance regimes. Based on a selective review of the literature, this article proposes a brief but systematic analysis of policy paradigms in the field of social assistance. Three ideal types that emphasize the ideational dimension of social assistance are analyzed, namely, the entitlement, workfare, and activation paradigms. The value of the typology lies in its utility for characterizing the ideational orientation of social assistance regimes. Specifically, the typology provides a yardstick for measuring the ideas of policy actors with respect to social assistance and can facilitate the conduct of case studies, comparative research, and causal analyses on this policy sector.

  14. Exploring Paradigms of Crime Reduction

    DEFF Research Database (Denmark)

    Soothill, Keith; Christoffersen, Mogens N.; Hussain, Azhar

    2010-01-01

    Using Danish registers for a 1980 birth cohort of 29,944 males with parental information and following up these cases for 25 years, the study considers four paradigms of crime reduction (parental child rearing, structural factors around adolescence, locality and individual resources). Focusing on...... have more widespread benefits, but the assumed causal links need to be further explored. The use of population registers, under controlled conditions, provides an important window on criminal careers....

  15. Storytelling, advertising and paradigm fusion

    OpenAIRE

    Anderson, David

    2012-01-01

    'The art of storytelling in the modern age is fundamentally important. So, how we create stories for a screen-based culture is vitally important to master' (Hegarty, 2011, p.96-97). This paper explores the potential benefit of fusing aspects of creative writing with the curriculum of the BA Creative Advertising programme (BACAP) at Leeds College of Art (LCA) in order to address Sir John Hegarty's assertion. In particular it will focus on the characteristics of the 'classical paradigms' us...

  16. Mandarin functional MRI Language paradigms

    OpenAIRE

    Ci, He; van Graan, Andre; Gonz?lvez, Gloria; Thompson, Pamela; Hill, Andrea; Duncan, John S.

    2016-01-01

    Abstract Objective The objective of this study was to implement convenient, fast, and accurate Mandarin task paradigms for functional MRI, and to locate the Chinese language functional areas in frontal and temporal lobes. Materials and Methods Nineteen healthy Chinese volunteers participated in this study, which utilized a block design with four language tasks: auditory naming (AN), picture naming (PN), verbal fluency?character (VFC), and verbal fluency?letter (VFL). All functional images wer...

  17. Introduction: Science, Sexuality, and Psychotherapy: Shifting Paradigms.

    Science.gov (United States)

    Cerbone, Armand R

    2017-08-01

    This introduction presents an overview of the current issue (73, 8) of Journal of Clinical Psychology: In Session. This issue features a series of articles, with clinical cases, each presented to illustrate the challenges faced by individuals and couples whose sexual and gender identities and expressions do not comport with traditional and cultural norms. These articles also document the challenges to the therapists who treat them. Considered individually, each article underscores the need to recognize the importance of evidence in guiding psychotherapy in cases involving sexuality. The discussions in each article offer recommendations meant to help and guide psychotherapists. Considered collectively, they raise important questions and considerations about shifting paradigms of human sexuality. Implications for assessment and treatment of cases involving sexuality and gender identity are discussed and recommended. © 2017 Wiley Periodicals, Inc.

  18. [Meta-legal paradigms of nanomedicine].

    Science.gov (United States)

    Pérez Alvarez, Salvador

    2012-01-01

    Nanomedicine is the Nanotechnology applied in the field of Medicine. Nanomedicine includes a wide range of technologies applied to devices, materials, medical procedures and treatment modalities are being developed, in some cases, through the convergence of living and nonliving materials. The developments in this scientific field are the prelude of a new era in health where Nanotechnology will provide, in a short period of time, substantial benefits for the general welfare and health of people with serious and incurable diseases using other more traditional medical treatments. This is, in brief, the object of this research that has been focused in the study of the ethical-legal paradigms that should inform the developments and expectations generated by medical applications of Nanotechnology.

  19. About hypotheses and paradigms: exploring the Discreetness-Chance Paradigm.

    Science.gov (United States)

    Kaellis, Eugene

    2006-01-01

    Hypotheses generally conform to paradigms which, over time, change, usually tardily, after they have become increasingly difficult to sustain under the impact of non-conforming evidence and alternative hypotheses, but more important, when they no longer are comfortably ensconced in the surrounding social-economic-political-cultural milieu. It is asserted that this milieu is the most important factor in shaping scientific theorizing. Some examples are cited: the rejection of the evidence that the world orbits around the sun (suspected by Pythagoras) in favor of centuries-long firm adherence to the Ptolemaic geocentric system; the early acceptance of Natural Selection in spite of its tautological essence and only conjectural supporting evidence, because it justified contemporaneous social-political ideologies as typified by, e.g., Spencer and Malthus. Economic, social, and cultural factors are cited as providing the ground, i.e., ideational substrate, for what is cited as the Discreetness-Chance Paradigm (DCP), that has increasingly dominated physics, biology, and medicine for over a century and which invokes small, discrete packets of energy/matter (quanta, genes, microorganisms, aberrant cells) functioning within an environment of statistical, not determined, causality. There is speculation on a possible paradigmatic shift from the DCP, which has fostered the proliferation, parallel with ("splitting") taxonomy, of alleged individual disease entities, their diagnoses, and, when available, their specific remedies, something particularly prominent in, e.g., psychiatry's Diagnostic and Statistical Manual, a codified compendium of alleged mental and behavioral disorders, but evident in any textbook of diagnosis and treatment of physical ailments. This presumed paradigm shift may be reflected in Western medicine, presently increasingly empirical and atomized, towards a growing acceptance of a more generalized, subject-oriented, approach to health and disease, a non

  20. A general method for the purification of synthetic oligodeoxyribonucleotides containing strong secondary structure by reversed-phase high-performance liquid chromatography on PRP-1 resin.

    Science.gov (United States)

    Germann, M W; Pon, R T; van de Sande, J H

    1987-09-01

    Synthetic 5'-dimethoxytritylated oligodeoxyribonucleotides, which contained strong secondary structure, were satisfactorily denatured and purified by reversed-phase HPLC on PRP-1 columns when strongly alkaline conditions (0.05 M NaOH) were employed. This procedure was suitable for the purification of hairpin structures, e.g., d(CG)nT4(CG)n (n = 4, 5, 6), and oligo(dG) sequences, e.g., d(G)24, as well as oligodeoxyribonucleotide probes which contained degenerate base sites. Oligodeoxyribonucleotides as long as 50 bases in length were purified. Recovery of injected oligonucleotides was typically 90% or better. The high capacity of the PRP-1 resin also allowed purification to be performed on a preparative scale (2-8 mg per injection). Enzymatic degradation and HPLC analysis indicated that no modification of the heterocyclic bases occurred under the alkaline conditions described.

  1. Reduced response of splenocytes after mitogen-stimulation in the prion protein (PrP) gene-deficient mouse: PrPLP/Doppel production and cerebral degeneration

    International Nuclear Information System (INIS)

    Kim, Chi-Kyeong; Hirose, Yuko; Sakudo, Akikazu; Takeyama, Natsumi; Kang, Chung-Boo; Taniuchi, Yojiro; Matsumoto, Yoshitsugu; Itohara, Shigeyoshi; Sakaguchi, Suehiro; Onodera, Takashi

    2007-01-01

    Splenocytes of wild-type (Prnp +/+ ) and prion protein gene-deficient (Prnp -/- ) mice were treated with various activation stimuli such as T cell mitogen concanavalin A (ConA), phorbol 12-myristate 13-acetate (PMA) + ionomycin (Io), or B cell mitogen lipopolysaccharide (LPS). Cellular prion protein (PrP C ) expression was enhanced following ConA stimulation, but not PMA + Io or LPS in Prnp +/+ splenocytes. Rikn Prnp -/- splenocytes elicited lower cell proliferations than Prnp +/+ or Zrch I Prnp -/- splenocytes after LPS stimulation and showed sporadic nerve cells in the cerebral cortex and deeper structure. Around the degenerated nerve cells, mild vacuolation in the neuropil was observed. This neural alteration correlated well to the suppressed response of B cells in the spleen. The finding that discrete lesions within the central nervous systems induced marked modulation of immune function probably indicates the existence of a delicately balanced neural-endocrine network by PrP C and PrPLP/Doppel

  2. Low fraction of the 222K PrP variant in the protease-resistant moiety of PrPres in heterozygous scrapie positive goats.

    Science.gov (United States)

    Mazza, Maria; Guglielmetti, Chiara; Ingravalle, Francesco; Brusadore, Sonia; Langeveld, Jan P M; Ekateriniadou, Loukia V; Andréoletti, Olivier; Casalone, Cristina; Acutis, Pier Luigi

    2017-07-01

    The presence of lysine (K) at codon 222 has been associated with resistance to classical scrapie in goats, but few scrapie cases have been identified in 222Q/K animals. To investigate the contribution of the 222K variant to PrPres formation in natural and experimental Q/K scrapie cases, we applied an immunoblotting method based on the use of two different monoclonal antibodies, F99/97.6.1 and SAF84, chosen for their different affinities to 222K and 222Q PrP variants. Our finding that PrPres seems to be formed nearly totally by the 222Q variant provides evidence that the 222K PrP variant confers resistance to conversion to PrPres formation and reinforces the view that this mutation has a protective role against classical scrapie in goats.

  3. Problem Periods

    Science.gov (United States)

    ... ovary syndrome. Read our information on PCOS for teens , and see your doctor if you think you may have PCOS. Major weight loss. Girls who have anorexia will often stop having periods. When to see ...

  4. PrP mRNA and protein expression in brain and PrP(c) in CSF in Creutzfeldt-Jakob disease MM1 and VV2.

    Science.gov (United States)

    Llorens, Franc; Ansoleaga, Belén; Garcia-Esparcia, Paula; Zafar, Saima; Grau-Rivera, Oriol; López-González, Irene; Blanco, Rosi; Carmona, Margarita; Yagüe, Jordi; Nos, Carlos; Del Río, José Antonio; Gelpí, Ellen; Zerr, Inga; Ferrer, Isidre

    2013-01-01

    Creutzfeldt-Jakob disease (CJD) is a heterogenic neurodegenerative disorder associated with abnormal post-translational processing of cellular prion protein (PrP(c)). CJD displays distinctive clinical and pathological features which correlate with the genotype at the codon 129 (methionine or valine: M or V respectively) in the prion protein gene and with size of the protease-resistant core of the abnormal prion protein PrP(sc) (type 1: 20/21 kDa and type 2: 19 kDa). MM1 and VV2 are the most common sporadic CJD (sCJD) subtypes. PrP mRNA expression levels in the frontal cortex and cerebellum are reduced in sCJD in a form subtype-dependent. Total PrP protein levels and PrP(sc) levels in the frontal cortex and cerebellum accumulate differentially in sCJD MM1 and sCJD VV2 with no relation between PrP(sc) deposition and spongiform degeneration and neuron loss, but with microgliosis, and IL6 and TNF-α response. In the CSF, reduced PrP(c), the only form present in this compartment, occurs in sCJD MM1 and VV2. PrP mRNA expression is also reduced in the frontal cortex in advanced stages of Alzheimer disease, Lewy body disease, progressive supranuclear palsy, and frontotemporal lobe degeneration, but PrP(c) levels in brain varies from one disease to another. Reduced PrP(c) levels in CSF correlate with PrP mRNA expression in brain, which in turn reflects severity of degeneration in sCJD.

  5. A Randomized Controlled Study of a Fully Liquid DTaP-IPV-HB-PRP-T Hexavalent Vaccine for Primary and Booster Vaccinations of Healthy Infants and Toddlers in Latin America.

    Science.gov (United States)

    López, Pío; Arguedas Mohs, Adriano; Abdelnour Vásquez, Arturo; Consuelo-Miranda, Maria; Feroldi, Emmanuel; Noriega, Fernando; Jordanov, Emilia; B Chir, Siham; Zambrano, Betzana

    2017-11-01

    Hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-HB-PRP-T)-containing vaccines are increasingly the standard of care. This study evaluated the primary series (NCT01177722) and booster (NCT01444781) of a fully liquid DTaP-IPV-HB-PRP-T vaccine in Latin America. Infants (N = 1375) received hepatitis B vaccine at birth and were randomized to one of 3 batches of the investigational DTaP-IPV-HB-PRP-T or licensed control vaccine (DTaP-HB-IPV//PRP-T) at 2-4 to 6 months of age, coadministered with 7-valent pneumococcal conjugate vaccine (PCV7) (2-4-6 months) and rotavirus vaccine (2-4 months). A booster of either DTaP-IPV-HB-PRP-T or control was given at 12-24 months, coadministered with PCV7. Immunogenicity was assessed by validated assays and safety from parental reports. Primary series seroprotection and vaccine response rates were equivalent for DTaP-IPV-HB-PRP-T batches. For pooled batches, noninferiority to the control vaccine was demonstrated for each antigen. There were no descriptive differences in antibody persistence or booster response between DTaP-IPV-HB-PRP-T and the control. The booster responses to either vaccine following DTaP-IPV-HB-PRP-T primary series or to DTaP-IPV-HB-PRP-T following a control vaccine primary series were similar. The anti-aP component (filamentous hemagglutinin [FHA] and pertussis toxin [PT]) vaccine response and anti-Haemophilus influenzae type b (PRP) series seroprotection (≥0.15 µg/mL) rates were ≥73.0% after 2 primary series doses. Antipyretics had no effect on the immune response, and an extra (oral) polio vaccination had no effect on the antipolio booster response. Responses to PCV7 and rotavirus vaccine were similar for each coadministration. There were no safety concerns observed with any vaccine. These results confirm the suitability of the fully liquid DTaP-IPV-HB-PRP-T vaccine for primary and booster vaccination of infants.

  6. Evidence that bank vole PrP is a universal acceptor for prions.

    Directory of Open Access Journals (Sweden)

    Joel C Watts

    2014-04-01

    Full Text Available Bank voles are uniquely susceptible to a wide range of prion strains isolated from many different species. To determine if this enhanced susceptibility to interspecies prion transmission is encoded within the sequence of the bank vole prion protein (BVPrP, we inoculated Tg(M109 and Tg(I109 mice, which express BVPrP containing either methionine or isoleucine at polymorphic codon 109, with 16 prion isolates from 8 different species: humans, cattle, elk, sheep, guinea pigs, hamsters, mice, and meadow voles. Efficient disease transmission was observed in both Tg(M109 and Tg(I109 mice. For instance, inoculation of the most common human prion strain, sporadic Creutzfeldt-Jakob disease (sCJD subtype MM1, into Tg(M109 mice gave incubation periods of ∼200 days that were shortened slightly on second passage. Chronic wasting disease prions exhibited an incubation time of ∼250 days, which shortened to ∼150 days upon second passage in Tg(M109 mice. Unexpectedly, bovine spongiform encephalopathy and variant CJD prions caused rapid neurological dysfunction in Tg(M109 mice upon second passage, with incubation periods of 64 and 40 days, respectively. Despite the rapid incubation periods, other strain-specified properties of many prion isolates--including the size of proteinase K-resistant PrPSc, the pattern of cerebral PrPSc deposition, and the conformational stability--were remarkably conserved upon serial passage in Tg(M109 mice. Our results demonstrate that expression of BVPrP is sufficient to engender enhanced susceptibility to a diverse range of prion isolates, suggesting that BVPrP may be a universal acceptor for prions.

  7. Transmissibility of H-Type Bovine Spongiform Encephalopathy to Hamster PrP Transgenic Mice.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Okada

    Full Text Available Two distinct forms of atypical bovine spongiform encephalopathies (H-BSE and L-BSE can be distinguished from classical (C- BSE found in cattle based on biochemical signatures of disease-associated prion protein (PrPSc. H-BSE is transmissible to wild-type mice-with infected mice showing a long survival period that is close to their normal lifespan-but not to hamsters. Therefore, rodent-adapted H-BSE with a short survival period would be useful for analyzing H-BSE characteristics. In this study, we investigated the transmissibility of H-BSE to hamster prion protein transgenic (TgHaNSE mice with long survival periods. Although none of the TgHaNSE mice manifested the disease during their lifespan, PrPSc accumulation was observed in some areas of the brain after the first passage. With subsequent passages, TgHaNSE mice developed the disease with a mean survival period of 220 days. The molecular characteristics of proteinase K-resistant PrPSc (PrPres in the brain were identical to those observed in first-passage mice. The distribution of immunolabeled PrPSc in the brains of TgHaNSE mice differed between those infected with H-BSE as compared to C-BSE or L-BSE, and the molecular properties of PrPres in TgHaNSE mice infected with H-BSE differed from those of the original isolate. The strain-specific electromobility, glycoform profiles, and proteolytic cleavage sites of H-BSE in TgHaNSE mice were indistinguishable from those of C-BSE, in which the diglycosylated form was predominant. These findings indicate that strain-specific pathogenic characteristics and molecular features of PrPres in the brain are altered during cross-species transmission. Typical H-BSE features were restored after back passage from TgHaNSE to bovinized transgenic mice, indicating that the H-BSE strain was propagated in TgHaNSE mice. This could result from the overexpression of the hamster prion protein.

  8. Reduced Hyperpolarization-Activated Current Contributes to Enhanced Intrinsic Excitability in Cultured Hippocampal Neurons from PrP(-/-) Mice.

    Science.gov (United States)

    Fan, Jing; Stemkowski, Patrick L; Gandini, Maria A; Black, Stefanie A; Zhang, Zizhen; Souza, Ivana A; Chen, Lina; Zamponi, Gerald W

    2016-01-01

    Genetic ablation of cellular prion protein (PrP(C)) has been linked to increased neuronal excitability and synaptic activity in the hippocampus. We have previously shown that synaptic activity in hippocampi of PrP-null mice is increased due to enhanced N-methyl-D-aspartate receptor (NMDAR) function. Here, we focused on the effect of PRNP gene knock-out (KO) on intrinsic neuronal excitability, and in particular, the underlying ionic mechanism in hippocampal neurons cultured from P0 mouse pups. We found that the absence of PrP(C) profoundly affected the firing properties of cultured hippocampal neurons in the presence of synaptic blockers. The membrane impedance was greater in PrP-null neurons, and this difference was abolished by the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker ZD7288 (100 μM). HCN channel activity appeared to be functionally regulated by PrP(C). The amplitude of voltage sag, a characteristic of activating HCN channel current (I h), was decreased in null mice. Moreover, I h peak current was reduced, along with a hyperpolarizing shift in activation gating and slower kinetics. However, neither HCN1 nor HCN2 formed a biochemical complex with PrP(C). These results suggest that the absence of PrP downregulates the activity of HCN channels through activation of a cell signaling pathway rather than through direct interactions. This in turn contributes to an increase in membrane impedance to potentiate neuronal excitability.

  9. Peroxiredoxin 6 promotes upregulation of the prion protein (PrP in neuronal cells of prion-infected mice

    Directory of Open Access Journals (Sweden)

    Wagner Wibke

    2012-12-01

    Full Text Available Abstract Background It has been widely established that the conversion of the cellular prion protein (PrPC into its abnormal isoform (PrPSc is responsible for the development of transmissible spongiform encephalopathies (TSEs. However, the knowledge of the detailed molecular mechanisms and direct functional consequences within the cell is rare. In this study, we aimed at the identification of deregulated proteins which might be involved in prion pathogenesis. Findings Apolipoprotein E and peroxiredoxin 6 (PRDX6 were identified as upregulated proteins in brains of scrapie-infected mice and cultured neuronal cell lines. Downregulation of PrP gene expression using specific siRNA did not result in a decrease of PRDX6 amounts. Interestingly, selective siRNA targeting PRDX6 or overexpression of PRDX6 controlled PrPC and PrPSc protein amounts in neuronal cells. Conclusions Besides its possible function as a novel marker protein in the diagnosis of TSEs, PDRX6 represents an attractive target molecule in putative pharmacological intervention strategies in the future.

  10. Paradigm for new scientific technology; Shinkagaku gijutsu paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Shindo, Y [National Chemical Lab. for Industry, Tokyo (Japan)

    1995-01-05

    This paper reviews the current status from the standpoint of chemical engineers facing the coming of the 21st century, and surveys the paradigm for new scientific technologies. The criticism is mixed with unique opinions everywhere, such as `departure of students from scientific and engineering faculties is none other than the result of a market principle`, `national burden of trillions of yens should not be spent only under a justice of advancement of the science`, and `the global civilization itself has no other way but to change from the conventional expansive development type of the western country style to the internal development type of the oriental country style`. Values that define the paradigm for new scientific technologies may include such keywords as saturation in technology, baseless expansion of research projects, criticism on science, market principle, and centering human being. It should be looked at seriously that profit from research and development should exceed the cast invested therein in the future, and scientific technologies that serve truly the society should be aimed at. These efforts will result in one of the large pillars that support the future in which creation of new functions is aimed at as a result of structuring the new systems. Trying to overcome the environmental problems is one of them.

  11. Cytoplasmic viral RNA-dependent RNA polymerase disrupts the intracellular splicing machinery by entering the nucleus and interfering with Prp8.

    Directory of Open Access Journals (Sweden)

    Yen-Chin Liu

    2014-06-01

    Full Text Available The primary role of cytoplasmic viral RNA-dependent RNA polymerase (RdRp is viral genome replication in the cellular cytoplasm. However, picornaviral RdRp denoted 3D polymerase (3D(pol also enters the host nucleus, where its function remains unclear. In this study, we describe a novel mechanism of viral attack in which 3D(pol enters the nucleus through the nuclear localization signal (NLS and targets the pre-mRNA processing factor 8 (Prp8 to block pre-mRNA splicing and mRNA synthesis. The fingers domain of 3D(pol associates with the C-terminal region of Prp8, which contains the Jab1/MPN domain, and interferes in the second catalytic step, resulting in the accumulation of the lariat form of the splicing intermediate. Endogenous pre-mRNAs trapped by the Prp8-3D(pol complex in enterovirus-infected cells were identified and classed into groups associated with cell growth, proliferation, and differentiation. Our results suggest that picornaviral RdRp disrupts pre-mRNA splicing processes, that differs from viral protease shutting off cellular transcription and translation which contributes to the pathogenesis of viral infection.

  12. Heparan sulfate proteoglycan is associated with amyloid plaques and neuroanatomically targeted PrP pathology throughout the incubation period of scrapie-infected mice

    NARCIS (Netherlands)

    McBride, P. A.; Wilson, M. I.; Eikelenboom, P.; Tunstall, A.; Bruce, M. E.

    1998-01-01

    Heparan sulfate proteoglycan (HSPG) has been found to be associated with amyloid deposits in a number of diseases including the cerebral amyloid plaques of Alzheimer's disease and the transmissible spongiform encephalopathies (TSEs). The role of HSPG in amyloid formation and the neurodegenerative

  13. The Paradigm of Distributed Creativity

    DEFF Research Database (Denmark)

    Glaveanu, Vlad Petre

    This presentation aims to focus on and develop the notion of distributed creativity from a cultural psychological perspective. It will start by outlining the need for a cultural psychological paradigm of creative expression and argue that this perspective is primarily concerned with what can...... be called ‘distributed creativity’. Drawing on related literature on distributed cognition (Hutchins, 2000), I will consider here the three inter-related ways in which creative action is distributed: across people, across people and objects, and across time. This particular understanding of creativity...

  14. Psychiatry beyond the current paradigm.

    LENUS (Irish Health Repository)

    Bracken, Pat

    2012-12-01

    A series of editorials in this Journal have argued that psychiatry is in the midst of a crisis. The various solutions proposed would all involve a strengthening of psychiatry\\'s identity as essentially \\'applied neuroscience\\'. Although not discounting the importance of the brain sciences and psychopharmacology, we argue that psychiatry needs to move beyond the dominance of the current, technological paradigm. This would be more in keeping with the evidence about how positive outcomes are achieved and could also serve to foster more meaningful collaboration with the growing service user movement.

  15. Intra-articular platelet-rich plasma (PRP) injections for treating knee pain associated with osteoarthritis of the knee in the Japanese population: a phase I and IIa clinical trial.

    Science.gov (United States)

    Taniguchi, Yu; Yoshioka, Tomokazu; Kanamori, Akihiro; Aoto, Katsuya; Sugaya, Hisashi; Yamazaki, Masashi

    2018-02-01

    Intra-articular platelet-rich plasma (PRP) injection has been found to be effective for treating osteoarthritis in patients from Western countries; however, the safety and efficacy of PRP have not been sufficiently investigated in Japanese patients. The present study aimed to evaluate the safety and feasibility of intra-articular PRP injection in Japanese patients with knee osteoarthritis. PRP without white blood cells was prepared using a single-spin centrifuge (PRGF-Endoret; BTI Biotechnology Institute, Vitoria, Spain). A 6-mL PRP volume was injected in the knee joint three times at 1 week intervals. All patients were prospectively evaluated before intervention and at 1, 3, and 6 months after the treatment. Adverse events, the Visual Analog Scale (VAS) pain score, Japanese Knee Osteoarthritis Measure (JKOM) score and Japanese Orthopedic Association score were evaluated. Ten patients (all women; average age, 60.6 years) were treated. Only minor adverse events after injection were noted, and symptoms resolved within 48 hours after the injection. The average VAS pain scores were 71.6 mm and 18.4 mm at baseline and the 6-month follow-up, respectively (P PRP injection likely represents a safe treatment option for Japanese patients with mild-to-moderate knee osteoarthritis, and has the potential to relieve pain for up to 6 months, but further study is needed to verify the efficacy.

  16. Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome.

    Science.gov (United States)

    Saturveithan, C; Premganesh, G; Fakhrizzaki, S; Mahathir, M; Karuna, K; Rauf, K; William, H; Akmal, H; Sivapathasundaram, N; Jaspreet, K

    2016-07-01

    Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option.

  17. Intra-articular Hyaluronic Acid (HA and Platelet Rich Plasma (PRP injection versus Hyaluronic acid (HA injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA: A Retrospective Study on Functional Outcome

    Directory of Open Access Journals (Sweden)

    Saturveithan C

    2016-07-01

    Full Text Available Introduction: Intra-articular hyaluronic acid (HA is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option.

  18. Semisynthetic prion protein (PrP) variants carrying glycan mimics at position 181 and 197 do not form fibrils† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc02719b Click here for additional data file.

    Science.gov (United States)

    Araman, Can; Thompson, Robert E.; Wang, Siyao; Hackl, Stefanie; Payne, Richard J.

    2017-01-01

    The prion protein (PrP) is an N-glycosylated protein attached to the outer leaflet of eukaryotic cell membranes via a glycosylphosphatidylinositol (GPI) anchor. Different prion strains have distinct glycosylation patterns and the extent of glycosylation of potentially pathogenic misfolded prion protein (PrPSc) has a major impact on several prion-related diseases (transmissible spongiform encephalopathies, TSEs). Based on these findings it is hypothesized that posttranslational modifications (PTMs) of PrP influence conversion of cellular prion protein (PrPC) into PrPSc and, as such, modified PrP variants are critical tools needed to investigate the impact of PTMs on the pathogenesis of TSEs. Here we report a semisynthetic approach to generate PrP variants modified with monodisperse polyethyleneglycol (PEG) units as mimics of N-glycans. Incorporating PEG at glycosylation sites 181 and 197 in PrP induced only small changes to the secondary structure when compared to unmodified, wildtype PrP. More importantly, in vitro aggregation was abrogated for all PEGylated PrP variants under conditions at which wildtype PrP aggregated. Furthermore, the addition of PEGylated PrP as low as 10 mol% to wildtype PrP completely blocked aggregation. A similar effect was observed for synthetic PEGylated PrP segments comprising amino acids 179–231 alone if these were added to wildtype PrP in aggregation assays. This behavior raises the question if large N-glycans interfere with aggregation in vivo and if PEGylated PrP peptides could serve as potential therapeutics. PMID:28989689

  19. Concomitant administration of a fully liquid, ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal serogroup C conjugate vaccine in infants.

    Science.gov (United States)

    Vesikari, Timo; Borrow, Ray; Da Costa, Xavier; Richard, Patrick; Eymin, Cécile; Boisnard, Florence; Lockhart, Stephen

    2017-01-11

    DTaP-IPV-HB-PRP-T or hexavalent vaccines are indicated for primary and booster vaccination of infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib). The present study evaluates the safety and immunogenicity of a ready-to-use hexavalent vaccine when co-administered with a meningococcal serogroup C conjugate (MenC) vaccine in infants. This was a phase III, open-label, randomised, multicentre study conducted in Finland. Healthy infants, aged 46-74days (n=350), were randomised in a ratio of 1:1 to receive DTaP-IPV-HB-PRP-T vaccine at two, three and four months, either with a MenC vaccine co-administered at two and four months (Group 1; n=175) or without MenC vaccine (Group 2; n=175). All infants also received routine rotavirus and 13-valent pneumococcal conjugate vaccines. The proportion of participants with an anti-HBs concentration ⩾10mIU/mL assessed one month after the third dose of DTaP-IPV-HB-PRP-T vaccine was 97.5% [95%CI: 93.1-99.3] in the coadministration group and 96.1% [95%CI: 91.8-98.6] in the group without MenC vaccine. The proportion of participants with an anti-MenC SBA titre ⩾8 assessed one month after the second dose of MenC vaccine was 100% in the coadministration group. Both primary objectives were achieved. Secondary immunogenicity and safety analyses showed that co-administration of DTaP-IPV-HB-PRP-T and MenC vaccines did not impact the immune response to the antigens of each of the two vaccines. All vaccines were well tolerated and the safety profile of DTaP-IPV-HB-PRP-T vaccine was similar in both groups. ClinicalTrials.gov identifier: NCT01839175; EudraCT number: 2012-005547-24. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  20. Functions for fission yeast splicing factors SpSlu7 and SpPrp18 in alternative splice-site choice and stress-specific regulated splicing.

    Directory of Open Access Journals (Sweden)

    Geetha Melangath

    Full Text Available Budding yeast spliceosomal factors ScSlu7 and ScPrp18 interact and mediate intron 3'ss choice during second step pre-mRNA splicing. The fission yeast genome with abundant multi-intronic transcripts, degenerate splice signals and SR proteins is an apt unicellular fungal model to deduce roles for core spliceosomal factors in alternative splice-site choice, intron retention and to study the cellular implications of regulated splicing. From our custom microarray data we deduce a stringent reproducible subset of S. pombe alternative events. We examined the role of factors SpSlu7 or SpPrp18 for these splice events and investigated the relationship to growth phase and stress. Wild-type log and stationary phase cells showed ats1+ exon 3 skipped and intron 3 retained transcripts. Interestingly the non-consensus 5'ss in ats1+ intron 3 caused SpSlu7 and SpPrp18 dependent intron retention. We validated the use of an alternative 5'ss in dtd1+ intron 1 and of an upstream alternative 3'ss in DUF3074 intron 1. The dtd1+ intron 1 non-canonical 5'ss yielded an alternative mRNA whose levels increased in stationary phase. Utilization of dtd1+ intron 1 sub-optimal 5' ss required functional SpPrp18 and SpSlu7 while compromise in SpSlu7 function alone hampered the selection of the DUF3074 intron 1 non canonical 3'ss. We analysed the relative abundance of these splice isoforms during mild thermal, oxidative and heavy metal stress and found stress-specific splice patterns for ats1+ and DUF3074 intron 1 some of which were SpSlu7 and SpPrp18 dependent. By studying ats1+ splice isoforms during compromised transcription elongation rates in wild-type, spslu7-2 and spprp18-5 mutant cells we found dynamic and intron context-specific effects in splice-site choice. Our work thus shows the combinatorial effects of splice site strength, core splicing factor functions and transcription elongation kinetics to dictate alternative splice patterns which in turn serve as an additional

  1. Emergence of two prion subtypes in ovine PrP transgenic mice infected with human MM2-cortical Creutzfeldt-Jakob disease prions.

    Science.gov (United States)

    Chapuis, Jérôme; Moudjou, Mohammed; Reine, Fabienne; Herzog, Laetitia; Jaumain, Emilie; Chapuis, Céline; Quadrio, Isabelle; Boulliat, Jacques; Perret-Liaudet, Armand; Dron, Michel; Laude, Hubert; Rezaei, Human; Béringue, Vincent

    2016-02-05

    Mammalian prions are proteinaceous pathogens responsible for a broad range of fatal neurodegenerative diseases in humans and animals. These diseases can occur spontaneously, such as Creutzfeldt-Jakob disease (CJD) in humans, or be acquired or inherited. Prions are primarily formed of macromolecular assemblies of the disease-associated prion protein PrP(Sc), a misfolded isoform of the host-encoded prion protein PrP(C). Within defined host-species, prions can exist as conformational variants or strains. Based on both the M/V polymorphism at codon 129 of PrP and the electrophoretic signature of PrP(Sc) in the brain, sporadic CJD is classified in different subtypes, which may encode different strains. A transmission barrier, the mechanism of which remains unknown, limits prion cross-species propagation. To adapt to the new host, prions have the capacity to 'mutate' conformationally, leading to the emergence of a variant with new biological properties. Here, we transmitted experimentally one rare subtype of human CJD, designated cortical MM2 (129 MM with type 2 PrP(Sc)), to transgenic mice overexpressing either human or the VRQ allele of ovine PrP(C). In marked contrast with the reported absence of transmission to knock-in mice expressing physiological levels of human PrP, this subtype transmitted faithfully to mice overexpressing human PrP, and exhibited unique strain features. Onto the ovine PrP sequence, the cortical MM2 subtype abruptly evolved on second passage, thereby allowing emergence of a pair of strain variants with distinct PrP(Sc) biochemical characteristics and differing tropism for the central and lymphoid tissues. These two strain components exhibited remarkably distinct replicative properties in cell-free amplification assay, allowing the 'physical' cloning of the minor, lymphotropic component, and subsequent isolation in ovine PrP mice and RK13 cells. Here, we provide in-depth assessment of the transmissibility and evolution of one rare subtype of

  2. Analysis of the Paradigm Evolution of Digital Libraries in China

    Directory of Open Access Journals (Sweden)

    Tan Sun

    2007-10-01

    Full Text Available The authors analyze the developmental framework of digital libraries in China and point out their current demand characteristics, development requirements, and developmental period. They then conclude that it is necessary to start up a new paradigm evolution of a digital library, from a traditional digital library to a virtual digital library. On that basis, they describe in detail several problems and developmental approaches that developing a virtual digital library must deal with, drawing lessons from the prototype DILIGENT.

  3. The detour paradigm in animal cognition.

    Science.gov (United States)

    Kabadayi, Can; Bobrowicz, Katarzyna; Osvath, Mathias

    2018-01-01

    In this paper, we review one of the oldest paradigms used in animal cognition: the detour paradigm. The paradigm presents the subject with a situation where a direct route to the goal is blocked and a detour must be made to reach it. Often being an ecologically valid and a versatile tool, the detour paradigm has been used to study diverse cognitive skills like insight, social learning, inhibitory control and route planning. Due to the relative ease of administrating detour tasks, the paradigm has lately been used in large-scale comparative studies in order to investigate the evolution of inhibitory control. Here we review the detour paradigm and some of its cognitive requirements, we identify various ecological and contextual factors that might affect detour performance, we also discuss developmental and neurological underpinnings of detour behaviors, and we suggest some methodological approaches to make species comparisons more robust.

  4. ENVIRONMENTALISM AND CLASSIC PARADIGMS OF INTERNATIONAL RELATIONS

    OpenAIRE

    D. D. Miniaeva

    2014-01-01

    This article examines an environmentalism integration process into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism) into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism). The main purpose of this study is to reveal the result of this integration. Methods used in this article include analysis and comparison of "ecological" paradigms on selected parameters (the nature of international relations, actors, ta...

  5. The Oral Paradigm and Snapchat

    Directory of Open Access Journals (Sweden)

    Oren Soffer

    2016-09-01

    Full Text Available In this short essay, I argue that the ephemeral nature of emerging instant-messaging applications, such as Snapchat, applies an oral paradigm. While online discourse of computer-mediated communication shares many qualities with oral communication, the case of ephemeral applications is unique, as the oral features are already integrated in the application technology design and as orality is often implemented on highly visual products. Snapchat applies technology that fades visual contents as if they were spoken words fading in the air after utterance. Moreover, Snapchat’s promise to delete all messages from its database after they are viewed echoes a key characteristic of primary oral culture: that is, the inability (and in our case, the obligation not to store knowledge. In this, Snapchat demonstrates counter-logic to the contemporary grammar of new media, which is based on information aggregation.

  6. Toward a New Energy Paradigm

    International Nuclear Information System (INIS)

    Farhad Mahmud

    2006-01-01

    More than 50% of the developing world does not have access to electricity. It is our belief that it is as much a problem of distribution as of production. The traditional approach of power distribution through a national grid system is remarkably slow. Alternate methods are not sought because of an implicit assumption that it is an area that would necessarily involve large infra-structural undertaking. However, the traditional distribution paradigm can be challenged by new developments in fuel cell technology that can open up the possibility of involvement of small private initiatives in the distribution of power in remote areas where grid penetration has not taken place. This would require distribution re-engineering in an innovative and practical way based on advancement in new technology (fuel cells in our case). Our business approach would require a shift in focus away from production to distribution in addressing the issue. (authors)

  7. Shield calculations, optimization vs. paradigm

    International Nuclear Information System (INIS)

    Cornejo D, N.; Hernandez S, A.; Martinez G, A.

    2006-01-01

    Many shieldings have been designed under the criteria of 'Maximum dose rates of project'. It has created the paradigm of those 'low dose rates', for the one which not few specialists would consider unacceptable levels of dose rate superior to the units of μSv.h -1 , independently of the exposure times. At the present time numerous shieldings are being designed considering dose restrictions in real times of exposure. After these new shieldings, the dose rates could be notably superior to those after traditional shieldings, without it implies inadequate designs or constructive errors. In the work significant differences in levels of dose rates and thickness of shieldings estimated by both methods for some typical facilities. It was concluded that the use of real times of exposure is more adequate for the optimization of the Radiological Protection, although this method demands bigger care in its application. (Author)

  8. Shielding calculations. Optimization vs. Paradigms

    International Nuclear Information System (INIS)

    Cornejo Diaz, Nestor; Hernandez Saiz, Alejandro; Martinez Gonzalez, Alina

    2005-01-01

    Many radiation shielding barriers in Cuba have been designed according to the criterion of Maxi-mum Projected Dose Rates. This fact has created the paradigm of low dose rates. Because of this, dose rate levels greater than units of Sv.h-1 would be considered unacceptable by many specialists, regardless of the real exposure times. Nowadays many shielding barriers are being designed using dose constraints in real exposure times. Behind the new barriers, dose rates could be notably greater than those behind the traditional ones, and it does not imply inadequate designs or constructive errors. In this work were obtained significant differences in dose rate levels and shield-ing thicknesses calculated by both methods for some typical installations. The work concludes that real exposure time approach is more adequate in order to optimise Radiation Protection, although this method should be carefully applied

  9. Emerging Paradigms in Machine Learning

    CERN Document Server

    Jain, Lakhmi; Howlett, Robert

    2013-01-01

    This  book presents fundamental topics and algorithms that form the core of machine learning (ML) research, as well as emerging paradigms in intelligent system design. The  multidisciplinary nature of machine learning makes it a very fascinating and popular area for research.  The book is aiming at students, practitioners and researchers and captures the diversity and richness of the field of machine learning and intelligent systems.  Several chapters are devoted to computational learning models such as granular computing, rough sets and fuzzy sets An account of applications of well-known learning methods in biometrics, computational stylistics, multi-agent systems, spam classification including an extremely well-written survey on Bayesian networks shed light on the strengths and weaknesses of the methods. Practical studies yielding insight into challenging problems such as learning from incomplete and imbalanced data, pattern recognition of stochastic episodic events and on-line mining of non-stationary ...

  10. The Risk-Benefit Paradigm vs the Causal Exposure Paradigm: LDL as a primary cause of vascular disease.

    Science.gov (United States)

    Toth, Peter P; Thanassoulis, George; Williams, Ken; Furberg, Curt D; Sniderman, Allan

    2014-01-01

    All current guidelines use the 10-year risk of a cardiovascular event to select subjects for statin primary preventive therapy. Benefit from therapy is stated to be determined by risk with the result that statin primary preventive therapy is initiated only when the risk of a cardiovascular event over the next decade exceeds a specified level. Thus all current guidelines are based primarily on the Risk-Benefit paradigm of primary prevention. The recent American Heart Association/American College of Cardiology guidelines differ from others in basing selection for statin therapy virtually exclusively on risk except for those few subjects with markedly elevated levels of low-density lipoprotein cholesterol (LDL-C). The Causal Exposure paradigm differs from the Risk-Benefit paradigm in that the objective of therapy is to prevent the anatomic disease within arterial walls that produces cardiovascular risk. Moreover, the anatomic disease and, therefore, the cardiovascular risk, is a function of the injurious action of the causal factors of vascular disease, such as blood pressure and LDL, on the arterial wall over long periods. In this article, we explain the strengths and weaknesses of both paradigms to provide a more secure framework to compare the strengths and weaknesses in the different cholesterol guidelines with particular emphasis on the evidence that the cardiovascular risk and the benefit from statin therapy is related to the level of LDL. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  11. Autologous US-guided PRP injection versus US-guided focal extracorporeal shock wave therapy for chronic lateral epicondylitis: A minimum of 2-year follow-up retrospective comparative study.

    Science.gov (United States)

    Alessio-Mazzola, Mattia; Repetto, Ilaria; Biti, Besmir; Trentini, Roberto; Formica, Matteo; Felli, Lamberto

    2018-01-01

    To compare the efficacy of two independent groups of patients treated with ultrasound (US)-guided extracorporeal shock wave (ESW) therapy and with US-guided injection of platelet-rich plasma (PRP) for chronic lateral epicondylitis (LE) with a minimum of 2-year follow-up. We retrospectively evaluated 63 patients treated for chronic LE (31 patients with autologous US-guided PRP injection and 32 patients with US-guided focal ESW therapy) from 2009 to 2014. All the patients were evaluated by means of Roles-Maudsley (RM) score, quick Disabilities of Arm, Shoulder, and Hand (QuickDASH) score, visual analogic scale (VAS) and patient-rated tennis elbow evaluation (PRTEE) to retrospectively assess the pain relief, level of activity, the self-reported function and subjective satisfaction at minimum of 2-year follow-up. Both US-guided autologous PRP injection and US-guided focal ESW administration proved effective in chronic LE with significant improvement in the QuickDASH, VAS, RM and PRTEE scores ( p 0.05). The mean time between treatment and symptom resolution was significantly shorter for the PRP treatment ( p = 0.0212); furthermore, the mean time to return to the normal activities was quicker for PRP group ( p = 0.0119). Both PRP injection and ESW therapy are feasible and safe options for the treatment of chronic LE with low risk of complications and with good long-term follow-up results. US-guided PRP injection has quick efficacy when compared with US-guided focal ESW therapy.

  12. Is This the Paradigm Shift We Need?

    Science.gov (United States)

    Mirvis, Jonathan

    2012-01-01

    Dr. Woocher's essay, states Mirvis, is seminal in the field of Jewish education. It proposes a new paradigm for Jewish education in North America. This proposed paradigm is supported by a comprehensive multi-disciplinary research drawing on literature from education, philosophy, history, sociology, psychology, and economics. The essay reflects a…

  13. Testing the membrane paradigm with holography

    NARCIS (Netherlands)

    de Boer, J.; Heller, M.P.; Pinzani-Fokeeva, N.

    2015-01-01

    One version of the membrane paradigm states that, as far as outside observers are concerned, black holes can be replaced by a dissipative membrane with simple physical properties located at the stretched horizon. We demonstrate that such a membrane paradigm is incomplete in several aspects. We argue

  14. Programming Paradigms in Computer Science Education

    OpenAIRE

    Bolshakova, Elena

    2005-01-01

    Main styles, or paradigms of programming – imperative, functional, logic, and object-oriented – are shortly described and compared, and corresponding programming techniques are outlined. Programming languages are classified in accordance with the main style and techniques supported. It is argued that profound education in computer science should include learning base programming techniques of all main programming paradigms.

  15. Towards a New Paradigm of Moral Personhood

    Science.gov (United States)

    Frimer, Jeremy A.; Walker, Lawrence J.

    2008-01-01

    Moral psychology is between paradigms. Kohlberg's model of moral rationality has proved inadequate in explaining action; yet its augmentation--moral personality--awaits empirical embodiment. This article addresses some critical issues in developing a comprehensive empirical paradigm of moral personhood. Is a first-person or a third-person…

  16. Efficacy of Platelet-Rich-Plasma (PRP and Highly Purified Bovine Xenograft (Laddec® Combination in Bone Regeneration after Cyst Enucleation: Radiological and Histological Evaluation

    Directory of Open Access Journals (Sweden)

    Sabrina Pappalardo

    2013-10-01

    Full Text Available Objectives: The purpose of the present study was to evaluate the efficacy of adding platelet-rich plasma (PRP to a new highly purified bovine allograft (Laddec® in the bone regeneration of cystic bony defects augmented following cystectomy.Material and Methods: Study sample included 20 patients undergoing cystectomy in which the bone defect was filled with PRP and Laddec®. All patients were examined with periapical radiographs before operation and at follow-up. After 3 months, at re-entry surgery for implant placement, bone core was taken for histological and histomorphometric analysis.Results: The postoperative successive radiographs showed a good regeneration of bone in the height of bony defects with application of PRP to bone graft. By the first postoperative month, about 48% of the defect was filled, which gradually increased in each month and showed about 90% of defect-fill by 6 months. Histological and histomorphometric analysis, showed a significant presence of bone tissue and vessels, with newly formed bone in contact with anorganic bone particles. The mean volume of vital bone was 68 ± 1.6% and the mean percentage of vital bone was 48 ± 2.4%. The mean percentage of inorganic particles in tissues was 20 ± 1.2% of the total volume. All the samples analyzed did not evidence the presence of inflammatory cells.Conclusions: The results of this study showed how the use of Laddec® in association with platelet-rich plasma allows bone regeneration and has a potential for routine clinical use for regeneration of cystic bony defects.

  17. Revisiting cytogenetic paradigms armed with new tools

    International Nuclear Information System (INIS)

    Cornforth, M.N.

    2003-01-01

    It could be argued that most of the fundamental tenets of radiation biology were either discovered, or subsequently confirmed, by observing eukaryotic chromosomes under the microscope. These include, but are certainly not limited to, dose-response relationships with respect to intensity (dose rate/dose fractionation) and radiation quality (LET/track structure). Chromosome aberrations are exquisitely sensitive indicators of radiation damage, and provide quantitative information of biological effect on a cell-by-cell-basis. As such, they have long been a favored endpoint for theoreticians, thereby figuring prominently in the development of generalized models of radiation action. Most of these seminal contributions to radiation biology occurred over a period of time when cytogenetic techniques were, of course, less refined than today. Considering the increasing rate at which technological advances have been made available to the researcher over the past few years, a reexamination of some of the radiological principles that cytogenetics helped to found seems in order. As an example of such effort, this talk will center around improvements to the use of whole chromosome painting by FISH- principally combinatorial painting techniques like mFISH and SKY- for the purposes of examining in greater detail structural aberrations to chromosomes produced following exposure to ionizing radiations of differing quality and intensity. This and related approaches by various laboratories around the world have turned up a few surprise discoveries that do not always fit established paradigms, and which serve to sharpen arguments that have been used to buttress existing models of aberration formation

  18. Understanding paradigms used for nursing research.

    Science.gov (United States)

    Weaver, Kathryn; Olson, Joanne K

    2006-02-01

    The aims of this paper are to add clarity to the discussion about paradigms for nursing research and to consider integrative strategies for the development of nursing knowledge. Paradigms are sets of beliefs and practices, shared by communities of researchers, which regulate inquiry within disciplines. The various paradigms are characterized by ontological, epistemological and methodological differences in their approaches to conceptualizing and conducting research, and in their contribution towards disciplinary knowledge construction. Researchers may consider these differences so vast that one paradigm is incommensurable with another. Alternatively, researchers may ignore these differences and either unknowingly combine paradigms inappropriately or neglect to conduct needed research. To accomplish the task of developing nursing knowledge for use in practice, there is a need for a critical, integrated understanding of the paradigms used for nursing inquiry. We describe the evolution and influence of positivist, postpositivist, interpretive and critical theory research paradigms. Using integrative review, we compare and contrast the paradigms in terms of their philosophical underpinnings and scientific contribution. A pragmatic approach to theory development through synthesis of cumulative knowledge relevant to nursing practice is suggested. This requires that inquiry start with assessment of existing knowledge from disparate studies to identify key substantive content and gaps. Knowledge development in under-researched areas could be accomplished through integrative strategies that preserve theoretical integrity and strengthen research approaches associated with various philosophical perspectives. These strategies may include parallel studies within the same substantive domain using different paradigms; theoretical triangulation to combine findings from paradigmatically diverse studies; integrative reviews; and mixed method studies. Nurse scholars are urged to

  19. Low fraction of the 222K PrP variant in the protease-resistant moiety of PrPres in heterozygous scrapie positive goats

    OpenAIRE

    Mazza, Maria; Guglielmetti, Chiara; Ingravalle, Francesco; Brusadore, Sonia; Langeveld, Jan P. M.; Ekateriniadou, Loukia V.; Andréoletti, Olivier; Casalone, Cristina; Acutis, Pier Luigi

    2017-01-01

    The presence of lysine (K) at codon 222 has been associated with resistance to classical scrapie in goats, but few scrapie cases have been identified in 222Q/K animals. To investigate the contribution of the 222K variant to PrPres formation in natural and experimental Q/K scrapie cases, we applied an immunoblotting method based on the use of two different monoclonal antibodies, F99/97.6.1 and SAF84, chosen for their different affinities to 222K and 222Q PrP variants. Our finding that PrPres s...

  20. Black holes: the membrane paradigm

    International Nuclear Information System (INIS)

    Thorne, K.S.; Price, R.H.; Macdonald, D.A.

    1986-01-01

    The physics of black holes is explored in terms of a membrane paradigm which treats the event horizon as a two-dimensional membrane embedded in three-dimensional space. A 3+1 formalism is used to split Schwarzschild space-time and the laws of physics outside a nonrotating hole, which permits treatment of the atmosphere in terms of the physical properties of thin slices. The model is applied to perturbed slowly or rapidly rotating and nonrotating holes, and to quantify the electric and magnetic fields and eddy currents passing through a membrane surface which represents a stretched horizon. Features of tidal gravitational fields in the vicinity of the horizon, quasars and active galalctic nuclei, the alignment of jets perpendicular to accretion disks, and the effects of black holes at the center of ellipsoidal star clusters are investigated. Attention is also given to a black hole in a binary system and the interactions of black holes with matter that is either near or very far from the event horizon. Finally, a statistical mechanics treatment is used to derive a second law of thermodynamics for a perfectly thermal atmosphere of a black hole

  1. Self-organized criticality paradigm

    International Nuclear Information System (INIS)

    Duran, I.; Stoeckel, J.; Hron, M.; Horacek, J.; Jakubka, K.; Kryska, L.

    2000-01-01

    According to the paradigm of the Self-Organized Criticality (SOC), the anomalous transport in tokamaks is caused by fast transient processes - avalanches. One of the manifestations of these phenomena should be 1/f decay of electrostatic fluctuations power spectra in a certain frequency range. In this paper, the frequency spectra of floating potential, density and fluctuation-induced flux, measured by poloidal and radial arrays of Langmuir probes on the CASTOR tokamak, are presented. The floating potential and the fluctuation-induced flux decay from 30 kHz up to 100 kHz as f -1 . The plasma density decays as f -1 in a more narrow band, 20 to 40 kHz. The possible limitation of SOC behavior for frequencies higher than 100 kHz due to intermittency is stressed. For this reason the Probability Distribution Functions (PDFs) of floating potential fluctuations were computed at different time scales using wavelet transform. A clear departure of the computed PDFs from Gaussianity, which is a classical signature of intermittency, is observed at time scales under 10 μs (100 kHz). (author)

  2. MDMA and the "ecstasy paradigm".

    Science.gov (United States)

    Cole, Jon C

    2014-01-01

    For nearly 30 years, there has been a steady flow of research papers highlighting the dangers of MDMA and the implications for ecstasy users. After such a long time, it would be reasonable to expect that these dangers would be obvious due to the large number of ecstasy users. The available evidence does not indicate that there are millions of ecstasy users experiencing any problems linked to their ecstasy use. The "precautionary principle" suggests that, in the absence of knowing for certain, "experts" should argue that MDMA be avoided. However, this may have been taken too far, as the dire warnings do not seem to be reducing with the lack of epidemiological evidence of clinically relevant problems. The "ecstasy paradigm" is one way of articulating this situation, in that the needs of research funders and publication bias lead to a specific set of subcultural norms around what information is acceptable in the public domain. By digging a little deeper, it is easy to find problems with the evidence base that informs the public debate around MDMA. The key question is whether it is acceptable to maintain this status quo given the therapeutic potential of MDMA.

  3. Cancer: shift of the paradigm.

    Science.gov (United States)

    Lichtenstein, Anatoly V

    2008-12-01

    Cancer is usually considered to be a by-product of design limitations of a multicellular organism and its intrinsic fallibility. However, recent data prompt a revision of some established notions about carcinogenesis and form a new paradigm of carcinogenesis as a highly conserved biological phenomenon - a programmed death of an organism. This altruistic program, which is unleashed when mutagenesis surpasses a certain critical threshold, gives a population the important benefit acting as a guardian of the gene pool against the spread of certain mutant genes. A growing body of evidence supports this point of view: (i) epigenetic changes leading to cancer arise early, simultaneously in many cells and look like deterministic regulation; (ii) concept of cancer stem cell suggests a view of carcinogenesis not as vague transformation but as well known differentiation; (iii) tumor/host relations usually perceived as antagonistic are, in reality, synergistic; (iv) death of an individual from cancer is predetermined and results apparently from a specific activity (killer function) of cancer cell and (v) evolutionary conservation indicates that cancer comes with a general advantage that explains its evolutionary success. A holistic approach to carcinogenesis suggests new avenues of research and new therapeutic strategy.

  4. An adaptive semantic matching paradigm for reliable and valid language mapping in individuals with aphasia.

    Science.gov (United States)

    Wilson, Stephen M; Yen, Melodie; Eriksson, Dana K

    2018-04-17

    Research on neuroplasticity in recovery from aphasia depends on the ability to identify language areas of the brain in individuals with aphasia. However, tasks commonly used to engage language processing in people with aphasia, such as narrative comprehension and picture naming, are limited in terms of reliability (test-retest reproducibility) and validity (identification of language regions, and not other regions). On the other hand, paradigms such as semantic decision that are effective in identifying language regions in people without aphasia can be prohibitively challenging for people with aphasia. This paper describes a new semantic matching paradigm that uses an adaptive staircase procedure to present individuals with stimuli that are challenging yet within their competence, so that language processing can be fully engaged in people with and without language impairments. The feasibility, reliability and validity of the adaptive semantic matching paradigm were investigated in sixteen individuals with chronic post-stroke aphasia and fourteen neurologically normal participants, in comparison to narrative comprehension and picture naming paradigms. All participants succeeded in learning and performing the semantic paradigm. Test-retest reproducibility of the semantic paradigm in people with aphasia was good (Dice coefficient = 0.66), and was superior to the other two paradigms. The semantic paradigm revealed known features of typical language organization (lateralization; frontal and temporal regions) more consistently in neurologically normal individuals than the other two paradigms, constituting evidence for validity. In sum, the adaptive semantic matching paradigm is a feasible, reliable and valid method for mapping language regions in people with aphasia. © 2018 Wiley Periodicals, Inc.

  5. Ostracism Online: A social media ostracism paradigm.

    Science.gov (United States)

    Wolf, Wouter; Levordashka, Ana; Ruff, Johanna R; Kraaijeveld, Steven; Lueckmann, Jan-Matthis; Williams, Kipling D

    2015-06-01

    We describe Ostracism Online, a novel, social media-based ostracism paradigm designed to (1) keep social interaction experimentally controlled, (2) provide researchers with the flexibility to manipulate the properties of the social situation to fit their research purposes, (3) be suitable for online data collection, (4) be convenient for studying subsequent within-group behavior, and (5) be ecologically valid. After collecting data online, we compared the Ostracism Online paradigm with the Cyberball paradigm (Williams & Jarvis Behavior Research Methods, 38, 174-180, 2006) on need-threat and mood questionnaire scores (van Beest & Williams Journal of Personality and Social Psychology 91, 918-928, 2006). We also examined whether ostracized targets of either paradigm would be more likely to conform to their group members than if they had been included. Using a Bayesian analysis of variance to examine the individual effects of the different paradigms and to compare these effects across paradigms, we found analogous effects on need-threat and mood. Perhaps because we examined conformity to the ostracizers (rather than neutral sources), neither paradigm showed effects of ostracism on conformity. We conclude that Ostracism Online is a cost-effective, easy to use, and ecologically valid research tool for studying the psychological and behavioral effects of ostracism.

  6. Evolution of the radiological protection paradigms

    International Nuclear Information System (INIS)

    Sordi, Gian Maria A.A.

    2009-01-01

    We consider as initial radiological protection paradigms those in vigour after the release of the atomic energy for pacific usages in 1955. In that occasion, only one paradigm was introduced, presently named dose limitation system. After arguing about the basis that raised the paradigm, we introduced the guidance, that is, the measurements to be implemented to comply with the paradigm. In that occasion, they were two, i.e., the radiation dose monitoring and the workplace classification. Afterwards, the reasons that caused the radiological protection paradigms changes in force until 1995 are discussed. The initial paradigm was modified introducing the justification and the optimization principles, adding that the radiological protection should be economical and effective. The guidance also increased to four: personal monitoring, workplace classification, reference level and workers classification. Afterwards, we give the main justifications for the present paradigms that besides the formers were added the dose constraints, the potential exposure and the annual risk limits. Due to these modifications, the workers classifications were eliminated from the guidance, but the potential exposure and the search for the dose constraints were added. Eventually, we discuss the tendencies for the next future and the main changes introduced by the ICRP in the Publication 103, 2007. (author)

  7. The Cognitive Paradigm Ontology: Design and Application

    Science.gov (United States)

    Laird, Angela R.

    2013-01-01

    We present the basic structure of the Cognitive Paradigm Ontology (CogPO) for human behavioral experiments. While the experimental psychology and cognitive neuroscience literature may refer to certain behavioral tasks by name (e.g., the Stroop paradigm or the Sternberg paradigm) or by function (a working memory task, a visual attention task), these paradigms can vary tremendously in the stimuli that are presented to the subject, the response expected from the subject, and the instructions given to the subject. Drawing from the taxonomy developed and used by the BrainMap project (www.brainmap.org) for almost two decades to describe key components of published functional imaging results, we have developed an ontology capable of representing certain characteristics of the cognitive paradigms used in the fMRI and PET literature. The Cognitive Paradigm Ontology is being developed to be compliant with the Basic Formal Ontology (BFO), and to harmonize where possible with larger ontologies such as RadLex, NeuroLex, or the Ontology of Biomedical Investigations (OBI). The key components of CogPO include the representation of experimental conditions focused on the stimuli presented, the instructions given, and the responses requested. The use of alternate and even competitive terminologies can often impede scientific discoveries. Categorization of paradigms according to stimulus, response, and instruction has been shown to allow advanced data retrieval techniques by searching for similarities and contrasts across multiple paradigm levels. The goal of CogPO is to develop, evaluate, and distribute a domain ontology of cognitive paradigms for application and use in the functional neuroimaging community. PMID:21643732

  8. Gas transmission : a paradigm shift

    International Nuclear Information System (INIS)

    Cornelson, D.W.

    1997-01-01

    The evolution of energy markets in North America was discussed. The investment opportunities that are possible in a deregulated energy market, be it in production or in the generation of energy commodities, in the development of midstream infrastructure, or in the provision of energy services, were outlined. Deregulation of crude oil, natural gas and electricity has resulted in significant changes in the structure of energy markets and the way in which customers are served. One of the advantages of competition regarding power generation is that it has turned energy into a commodity which has resulted in greater customer choice and efficiency. As one example of midstream infrastructure development, the Alliance Pipeline project was described. This project was conceived as a means to enhance the value of western Canadian natural gas. The 1,900 mile pipeline will run from British Columbia, through Alberta into Chicago where it will interconnect with the North American gas transmission grid. The pipeline is an efficient means of transporting energy from Western Canada to North American markets, and Alliance, as a lowest cost transporter, will continue to put pressure on the traditional infrastructure to become even more competitive at the margin. As such, Alliance represents a paradigm shift in energy transportation, and serves as an excellent example of the type of investment opportunity that a deregulated market can provide. It was suggested that innovation and competition in a deregulated North American energy market will continue to increase. As electricity is deregulated, the energy market will respond more quickly to changes in supply and demand than it did in the past, in an effort to satisfy the needs of investors and customers. This will provide increased opportunities for restructuring and further competition

  9. PARADIGM OF EDUCATION FOR THE INFORMATION SOCIETY

    Directory of Open Access Journals (Sweden)

    Yuriy M. Bogachkov

    2015-10-01

    Full Text Available Considering total crisis in education in Informational Age, we suggest that to overcome the crisis, it is necessary to promote pedagogical science up from "pre-paradigm stage” to the "paradigm stage". For this purpose it is necessary to separate the "educational science" from "education." “Educational paradigm” in such study will be the subject of the science. The key concepts for the "pedagogical paradigm" should be the concepts of "educational practice", "class of problems" and "educational text". We offer some axioms around these concepts.

  10. The Prerequisites for a Degrowth Paradigm Shift

    DEFF Research Database (Denmark)

    Buch-Hansen, Hubert

    2018-01-01

    What would it take for a degrowth paradigm shift to take place? Drawing on contemporary critical political economy scholarship, this article identifies four prerequisites for socio-economic paradigm shifts: deep crisis, an alternative political project, a comprehensive coalition of social forces...... currently facing humanity. On the other hand, the prospects for a degrowth paradigm shift remain bleak: unlike political projects that became hegemonic in the past, degrowth has neither support from a comprehensive coalition of social forces nor any consent to its agenda among the broader population....

  11. Female Poverty in Development Paradigm

    OpenAIRE

    PEKER, Ayşe Esra

    2018-01-01

    The scope  of  poverty differs  from country tocountry,  from the  period to period,  and  depending on  the  developments in welfare  level.  Today, although  the  phenomenon poverty is seen  the problem  of   less developed  and   developing c...

  12. Effects of the Pathogenic Mutation A117V and the Protective Mutation H111S on the Folding and Aggregation of PrP106-126: Insights from Replica Exchange Molecular Dynamics Simulations.

    Directory of Open Access Journals (Sweden)

    Lulu Ning

    Full Text Available The fragment 106-126 of prion protein exhibits similar properties to full-length prion. Experiments have shown that the A117V mutation enhances the aggregation of PrP106-126, while the H111S mutation abolishes the assembly. However, the mechanism of the change in the aggregation behavior of PrP106-126 upon the two mutations is not fully understood. In this study, replica exchange molecular dynamics simulations were performed to investigate the conformational ensemble of the WT PrP106-126 and its two mutants A117V and H111S. The obtained results indicate that the three species are all intrinsically disordered but they have distinct morphological differences. The A117V mutant has a higher propensity to form β-hairpin structures than the WT, while the H111S mutant has a higher population of helical structures. Furthermore, the A117V mutation increases the hydrophobic solvent accessible surface areas of PrP106-126 and the H111S mutation reduces the exposure of hydrophobic residues. It can be concluded that the difference in populations of β-hairpin structures and the change of hydrophobic solvent accessible areas may induce the different aggregation behaviors of the A117V and the H111S mutated PrP106-126. Understanding why the two mutations have contrary effects on the aggregation of PrP106-126 is very meaningful for further elucidation of the mechanism underlying aggregation and design of inhibitor against aggregation process.

  13. Absence of Evidence for a Causal Link between Bovine Spongiform Encephalopathy Strain Variant L-BSE and Known Forms of Sporadic Creutzfeldt-Jakob Disease in Human PrP Transgenic Mice.

    Science.gov (United States)

    Jaumain, Emilie; Quadrio, Isabelle; Herzog, Laetitia; Reine, Fabienne; Rezaei, Human; Andréoletti, Olivier; Laude, Hubert; Perret-Liaudet, Armand; Haïk, Stéphane; Béringue, Vincent

    2016-12-01

    Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt-Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between the host cellular prion protein (PrP C ) and the infecting pathological PrP assemblies (PrP Sc ) constituting the prion. A BSE strain variant, designated L-BSE and responsible for atypical, supposedly spontaneous forms of prion diseases in aged cattle, demonstrates zoonotic potential, as evidenced by its capacity to propagate more easily than classical BSE in transgenic mice expressing human PrP C and in nonhuman primates. In humanized mice, L-BSE propagates without any apparent species barrier and shares similar biochemical PrP Sc signatures with the CJD subtype designated MM2-cortical, thus opening the possibility that certain CJD cases classified as sporadic may actually originate from L-type BSE cross-transmission. To address this issue, we compared the biological properties of L-BSE and those of a panel of CJD subtypes representative of the human prion strain diversity using standard strain-typing criteria in human PrP transgenic mice. We found no evidence that L-BSE causes a known form of sporadic CJD. Since the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD, and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Brain regional networks active during the mismatch negativity vary with paradigm.

    Science.gov (United States)

    MacLean, Shannon E; Blundon, Elizabeth G; Ward, Lawrence M

    2015-08-01

    We used independent component analysis (ICA) of high-density EEG recordings coupled with single dipole fitting to identify the dominant brain regions active during the MMN in two different versions of a passive oddball paradigm: a simple, monotic, frequency-deviant paradigm and a more complex, dichotic, frequency-deviant paradigm with deviants occurring in either ear alone or in both ears at the same time. In both paradigms we found brain regional sources in the temporal and frontal cortices active during the MMN period, consistent with some previous studies. In the simpler paradigm, the scalp-potential variance during the earlier (70-120 ms) MMN was mostly accounted for by a wide array of temporal, frontal, and parietal sources. In the more complex paradigm, however, a generator in the prefrontal cortex accounted for a substantial amount of the variance of the scalp potential during the somewhat later MMN period (120-200 ms). These findings are consistent with a more nuanced view of the MMN and its generators than has been held in the past. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Glycosylphosphatidylinositol Anchor Modification Machinery Deficiency Is Responsible for the Formation of Pro-Prion Protein (PrP) in BxPC-3 Protein and Increases Cancer Cell Motility*

    Science.gov (United States)

    Yang, Liheng; Gao, Zhenxing; Hu, Lipeng; Wu, Guiru; Yang, Xiaowen; Zhang, Lihua; Zhu, Ying; Wong, Boon-Seng; Xin, Wei; Sy, Man-Sun; Li, Chaoyang

    2016-01-01

    The normal cellular prion protein (PrP) is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein. However, in pancreatic ductal adenocarcinoma cell lines, such as BxPC-3, PrP exists as a pro-PrP retaining its glycosylphosphatidylinositol (GPI) peptide signaling sequence. Here, we report the identification of another pancreatic ductal adenocarcinoma cell line, AsPC-1, which expresses a mature GPI-anchored PrP. Comparison of the 24 genes involved in the GPI anchor modification pathway between AsPC-1 and BxPC-3 revealed 15 of the 24 genes, including PGAP1 and PIG-F, were down-regulated in the latter cells. We also identified six missense mutations in DPM2, PIG-C, PIG-N, and PIG-P alongside eight silent mutations. When BxPC-3 cells were fused with Chinese hamster ovary (CHO) cells, which lack endogenous PrP, pro-PrP was successfully converted into mature GPI-anchored PrP. Expression of the individual gene, such as PGAP1, PIG-F, or PIG-C, into BxPC-3 cells does not result in phosphoinositide-specific phospholipase C sensitivity of PrP. However, when PIG-F but not PIG-P is expressed in PGAP1-expressing BxPC-3 cells, PrP on the surface of the cells becomes phosphoinositide-specific phospholipase C-sensitive. Thus, low expression of PIG-F and PGAP1 is the major factor contributing to the accumulation of pro-PrP. More importantly, BxPC-3 cells expressing GPI-anchored PrP migrate much slower than BxPC-3 cells bearing pro-PrP. In addition, GPI-anchored PrP-bearing AsPC-1 cells also migrate slower than pro-PrP bearing BxPC-3 cells, although both cells express filamin A. “Knocking out” PRNP in BxPC-3 cell drastically reduces its migration. Collectively, these results show that multiple gene irregularity in BxPC-3 cells is responsible for the formation of pro-PrP, and binding of pro-PrP to filamin A contributes to enhanced tumor cell motility. PMID:26683373

  16. Glycosylphosphatidylinositol Anchor Modification Machinery Deficiency Is Responsible for the Formation of Pro-Prion Protein (PrP) in BxPC-3 Protein and Increases Cancer Cell Motility.

    Science.gov (United States)

    Yang, Liheng; Gao, Zhenxing; Hu, Lipeng; Wu, Guiru; Yang, Xiaowen; Zhang, Lihua; Zhu, Ying; Wong, Boon-Seng; Xin, Wei; Sy, Man-Sun; Li, Chaoyang

    2016-02-19

    The normal cellular prion protein (PrP) is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein. However, in pancreatic ductal adenocarcinoma cell lines, such as BxPC-3, PrP exists as a pro-PrP retaining its glycosylphosphatidylinositol (GPI) peptide signaling sequence. Here, we report the identification of another pancreatic ductal adenocarcinoma cell line, AsPC-1, which expresses a mature GPI-anchored PrP. Comparison of the 24 genes involved in the GPI anchor modification pathway between AsPC-1 and BxPC-3 revealed 15 of the 24 genes, including PGAP1 and PIG-F, were down-regulated in the latter cells. We also identified six missense mutations in DPM2, PIG-C, PIG-N, and PIG-P alongside eight silent mutations. When BxPC-3 cells were fused with Chinese hamster ovary (CHO) cells, which lack endogenous PrP, pro-PrP was successfully converted into mature GPI-anchored PrP. Expression of the individual gene, such as PGAP1, PIG-F, or PIG-C, into BxPC-3 cells does not result in phosphoinositide-specific phospholipase C sensitivity of PrP. However, when PIG-F but not PIG-P is expressed in PGAP1-expressing BxPC-3 cells, PrP on the surface of the cells becomes phosphoinositide-specific phospholipase C-sensitive. Thus, low expression of PIG-F and PGAP1 is the major factor contributing to the accumulation of pro-PrP. More importantly, BxPC-3 cells expressing GPI-anchored PrP migrate much slower than BxPC-3 cells bearing pro-PrP. In addition, GPI-anchored PrP-bearing AsPC-1 cells also migrate slower than pro-PrP bearing BxPC-3 cells, although both cells express filamin A. "Knocking out" PRNP in BxPC-3 cell drastically reduces its migration. Collectively, these results show that multiple gene irregularity in BxPC-3 cells is responsible for the formation of pro-PrP, and binding of pro-PrP to filamin A contributes to enhanced tumor cell motility. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Beyond desertification: New paradigms for dryland landscapes

    Science.gov (United States)

    The dryland desertification paradigm focuses on losses of ecosystem services accompanying transitions from grasslands to systems dominated by bare ground or woody plants unpalatable for domestic livestock. However, recent studies reveal complex transitions across a range of environmental conditions ...

  18. The safety implications of emerging software paradigms

    International Nuclear Information System (INIS)

    Suski, G.J.; Persons, W.L.; Johnson, G.L.

    1994-10-01

    This paper addresses some of the emerging software paradigms that may be used in developing safety-critical software applications. Paradigms considered in this paper include knowledge-based systems, neural networks, genetic algorithms, and fuzzy systems. It presents one view of the software verification and validation activities that should be associated with each paradigm. The paper begins with a discussion of the historical evolution of software verification and validation. Next, a comparison is made between the verification and validation processes used for conventional and emerging software systems. Several verification and validation issues for the emerging paradigms are discussed and some specific research topics are identified. This work is relevant for monitoring and control at nuclear power plants

  19. Major Development Communication Paradigms and Practices ...

    African Journals Online (AJOL)

    info

    major paradigms of development and communication practices on graphic ... mobilize, educate and persuade target audience to support human development ... facilitates the understanding of the themes, issues and facts of a campaign.

  20. Dissonance: scientific paradigms underpinning the study of sound in geography

    Directory of Open Access Journals (Sweden)

    Daniel Paiva

    2018-05-01

    Full Text Available The objective of this article is to approach the different conceptions of sound – and its relations to the underlying scientific paradigms – that emerged throughout the history of geography. There has been a growing interest among geographers in understanding the spatialities of sound, and geographies of sound have become an emerging subfield of the discipline. For this reason, it is the right time to address how the discipline has approached sound throughout its history. Several theoretical perspectives influenced geography in the twentieth century, changing its methodologies and how its subjects were conceived. Sound, like other subjects, has been conceived very differently by geographers of competing paradigms. Concepts such as noise, soundscape, or sound as affect, among others, have dominated geographies of sound at specific periods. Due to the marginality of the subject in the discipline, assessments of these conceptual shifts are rare. I tackle this issue in this article as I provide a first attempt of writing a history of sound in geography. The article reviews debates regarding the name of the subfield, and the conceptions of sound in the successive and competing scientific paradigms in geography.

  1. New Indivisible Planetary Science Paradigm: Consequence of Questioning Popular Paradigms

    Science.gov (United States)

    Marvin Herndon, J.

    2014-05-01

    Progress in science involves replacing less precise understanding with more precise understanding. In science and in science education one should always question popular ideas; ask "What's wrong with this picture?" Finding limitations, conflicts or circumstances that require special ad hoc consideration sometimes is the key to making important discoveries. For example, from thermodynamic considerations, I found that the 'standard model of solar system formation' leads to insufficiently massive planetary cores. That understanding led me to discover a new indivisible planetary science paradigm. Massive-core planets formed by condensing and raining-out from within giant gaseous protoplanets at high pressures and high temperatures, accumulating heterogeneously on the basis of volatility with liquid core-formation preceding mantle-formation; the interior states of oxidation resemble that of the Abee enstatite chondrite. Core-composition was established during condensation based upon the relative solubilities of elements, including uranium, in liquid iron in equilibrium with an atmosphere of solar composition at high pressures and high temperatures. Uranium settled to the central region and formed planetary nuclear fission reactors, producing heat and planetary magnetic fields. Earth's complete condensation included a ~300 Earth-mass gigantic gas/ice shell that compressed the rocky kernel to about 66% of Earth's present diameter. T-Tauri eruptions, associated with the thermonuclear ignition of the Sun, stripped the gases away from the Earth and the inner planets. The T-Tauri outbursts stripped a portion of Mercury's incompletely condensed protoplanet and transported it to the region between Mars and Jupiter where it fused with in-falling oxidized condensate from the outer regions of the Solar System, forming the parent matter of ordinary chondrite meteorites, the main-Belt asteroids, and veneer for the inner planets, especially Mars. With its massive gas/ice shell

  2. A Viable Paradigm for Quantum Reality

    Science.gov (United States)

    Srivastava, Jagdish

    2010-10-01

    After a brief discussion of the EPR paradox, Bell's inequality, and Aspect's experiment, arguments will be presented in favor of the following statements: ``As it stands, Quantum mechanics is incomplete. There is further hidden structure, which would involve variables. No influence can move faster than light. The wave function is one whole thing and any change in its structure instantly influences its outcomes. Bell's theorem has not been applied correctly. There is a better paradigm.'' The said paradigm will be presented.

  3. International business and the eclectic paradigm

    DEFF Research Database (Denmark)

    The eclectic paradigm has become the dominant theoretical basis in the study of international business, multinational corporations and internationalization since 1980. However, developments such as economic globalization and the subsequent growth of global and alliance capitalism have fundamentally......, finance, evolutionary economics, resource-based theory or strategic management? Can it be utilized to explain new developments in international business and economics? Do these require new ideas and concepts to be integrated within the eclectic paradigm? What are the new challenges to which international...

  4. Project management: a new service delivery paradigm

    Directory of Open Access Journals (Sweden)

    G. van der Walt

    2007-07-01

    Full Text Available In line with international trends in governance, the South African Government’s initial focus on the development of policy frameworks, structures and systems in order to give effect to the values and principles of the Constitution, shifted to the most critical issue, namely service delivery. The Government became increasingly aware that a significant expansion in the scope and quality of service provision was not possible with traditional delivery settings and approaches. There is growing evidence that there is a need for a significant departure from conventional approaches and that a leap into a new service delivery paradigm is necessary. Increasingly this new paradigm highlights the need to further develop the government’s project management skills and applications with a view to achieving improved delivery capability. In this article the focus will be placed on the changing service delivery paradigm – from an “old” traditional model through the transition to a “new” paradigm. This paradigm is shaped by international and national trends and events in government. The contribution and advantages of project management applications for effective governance are highlighted and the article concludes with an explanation of project management organisational arrangements necessary to support the new paradigm.

  5. Caribbean ciguatera: a changing paradigm

    Directory of Open Access Journals (Sweden)

    T.R Tosteson

    2004-09-01

    Full Text Available Analyses of ciguatoxicity in the great barracuda Sphyraena barracuda and quantity of toxic benthic dinoflagellates on coastal reefs (correlated with the number of cases of human ciguatera intoxications in Puerto Rico were used to construct a model formulated on data obtained during the period of 1985-1988. The validity of the proposed model has been questioned by recent data obtained during the period of 1990-2000. Barracuda ciguatoxicity no longer showed a prominent seasonality while the fraction of randomly caught barracuda that were ciguatoxic significantly increased during this period. These two changes, accompanied by the discovery that ciguatoxic fish contained a variety of multiple toxins, appear to be correlated with the steadily increasing periods of elevated sea surface temperatures in this regionPruebas de ciguatoxicidad en la gran barracuda, Sphyraena barracuda y la cantidad de dinoflagelados bentónicos tóxicos en los arrecifes de la costa están correlacionados con el número de casos de intoxicaciones por ciguatera en humanos, en Puerto Rico. Estos hechos fueron utilizados para construir un modelo que fue formulado con la información recopilada durante el período de 1985- 1988. La validez de este modelo propuesto ha sido cuestionada debido a la información recientemente obtenida durante el período 1990-2000. La ciguatoxicidad en la barracuda ya no demostraba una marcada asociación con las temporadas mientras que la cantidad de barracuda ciguatóxica capturada al azar tuvo un aumento significativo durante este período. Estos dos cambios estuvieron acompañados por el descubrimiento de que peces ciguatóxicos contienen una gran variedad de toxinas que parecen estar relacionadas con los períodos de elevadas temperaturas en la superficie del mar. Estas temperaturas continúan aumentando de manera que a su vez continúan en un aumento estable en esta región

  6. Active training paradigm for motor imagery BCI.

    Science.gov (United States)

    Li, Junhua; Zhang, Liqing

    2012-06-01

    Brain-computer interface (BCI) allows the use of brain activities for people to directly communicate with the external world or to control external devices without participation of any peripheral nerves and muscles. Motor imagery is one of the most popular modes in the research field of brain-computer interface. Although motor imagery BCI has some advantages compared with other modes of BCI, such as asynchronization, it is necessary to require training sessions before using it. The performance of trained BCI system depends on the quality of training samples or the subject engagement. In order to improve training effect and decrease training time, we proposed a new paradigm where subjects participated in training more actively than in the traditional paradigm. In the traditional paradigm, a cue (to indicate what kind of motor imagery should be imagined during the current trial) is given to the subject at the beginning of a trial or during a trial, and this cue is also used as a label for this trial. It is usually assumed that labels for trials are accurate in the traditional paradigm, although subjects may not have performed the required or correct kind of motor imagery, and trials may thus be mislabeled. And then those mislabeled trials give rise to interference during model training. In our proposed paradigm, the subject is required to reconfirm the label and can correct the label when necessary. This active training paradigm may generate better training samples with fewer inconsistent labels because it overcomes mistakes when subject's motor imagination does not match the given cues. The experiments confirm that our proposed paradigm achieves better performance; the improvement is significant according to statistical analysis.

  7. Cancer research in need of a scientific revolution: Using `paradigm ...

    Indian Academy of Sciences (India)

    It has been proposed that science proceeds not only by accumulating data but also through paradigm shifts. Here, we propose to use the concept of `paradigm shift' as a method of investigation when dominant paradigms fail to achieve their promises. The first step in using the `paradigm shift' method in cancer research ...

  8. ENVIRONMENTALISM AND CLASSIC PARADIGMS OF INTERNATIONAL RELATIONS

    Directory of Open Access Journals (Sweden)

    D. D. Miniaeva

    2014-06-01

    Full Text Available This article examines an environmentalism integration process into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism into Three classical paradigms of international relations theory (Liberalism, Realism and Marxism. The main purpose of this study is to reveal the result of this integration. Methods used in this article include analysis and comparison of "ecological" paradigms on selected parameters (the nature of international relations, actors, targets, tools, processes. Results of research show that the beginning of the XXI century is distinguished by the development of new types of political concepts that explain interaction of elements in modern international relations in the area of environmental protection. The reason of these changes lies in the phenomena of environmentalism integration into Three paradigms of international relations. However, we cannot say that any of the examined paradigms accumulated all features of environmentalism without their modification. Better to say, it's rather similar to adaptation of environmental ideas. Therefore, to understand modern international relations processes, it is necessary to take into account their environmental element. Purchase on Elibrary.ru > Buy nowDOI: http://dx.doi.org/10.12731/2070-7568-2014-3-4

  9. Dodecylphosphocholine Micelles Induce Amyloid Formation of the PrP(110-136 Peptide via an α-Helical Metastable Conformation.

    Directory of Open Access Journals (Sweden)

    Simon Sauvé

    Full Text Available A peptide encompassing the conserved hydrophobic region and the first β-strand of the prion protein (PrP(110-136 shown to interact with the surface of dodecylphosphocholine micelles adopts an α-helical conformation that is localized below the head-group layer. This surface-bound peptide has a half-life of one day, and readily initiates the formation of amyloid fibrils. The presence of the latter was confirmed using birefringence microscopy upon Congo red binding and thioflavin T-binding induced fluorescence. The observation of this metastable α-helical conformer provides a unique snapshot of the early steps of the inter-conversion pathway. These findings together with the body of evidence from the prion literature allowed us to propose a mechanism for the conversion of PrPC to amyloid material.

  10. Bion and the sublime: the origins of an aesthetic paradigm.

    Science.gov (United States)

    Civitarese, Giuseppe

    2014-12-01

    In constructing his theory Bion drew on a number of symbolic matrices: psychoanalysis, philosophy, mathematics, literature, aesthetics. The least investigated of these is the last. True, we know that Bion cites many authors of the Romantic period, such as Coleridge, Keats, Blake and Wordsworth, as well as others who were held in high esteem in the Romantic period, such as Milton. However, less is known about the influence exerted on him by the aesthetics of the sublime, which while chronologically preceding Romanticism is in fact one of its components. My working hypothesis is that tracing a number of Bion's concepts back to this secret model can serve several purposes: firstly, it contributes to the study of the sources, and, secondly, it makes these concepts appear much less occasional and idiosyncratic than we might believe, being as they are mostly those less immediately understandable but not less important (O, negative capability, nameless dread, the infinite, the language of achievement, unison etc.). Finally, connecting these notions to a matrix, that is, disclosing the meaning of elements that are not simply juxtaposed but dynamically interrelated, in my view significantly increases not only their theoretical intelligibility but also their usefulness in clinical practice. In conclusion, one could legitimately argue that Bion gradually subsumed all the other paradigms he drew on within the aesthetic paradigm. Copyright © 2014 Institute of Psychoanalysis.

  11. Effects of FlAsH/Tetracysteine (TC) tag on PrP proteolysis and PrPres formation by TC-scanning

    Science.gov (United States)

    Taguchi, Yuzuru; Hohsfield, Lindsay A.; Hollister, Jason R.

    2014-01-01

    The FlAsH/tetracysteine (FlAsH/TC) tag is a powerful tool for fluorescent labeling of proteins. However, even small tags such as FlAsH/TC could alter the behavior of the tagged proteins, especially if the insertion occurs at internal sites. Defining the influence of FlAsH/TC on nearby protein-protein interactions might aid in selecting appropriate positions for internal TC insertions and allow the exploitation of serial FlAsH/TC insertions (TC-scanning) as a probe to characterize sites of protein-protein interaction. To explore this application in the context of substrate-protease interactions, we analyzed the effect of FlAsH/TC insertions on proteolysis of cellular prion protein (PrPsen) in in vitro reactions and generation of the C1 metabolic fragment of PrPsen in live neuroblastoma cells. The influence of FlAsH/TC insertion was evaluated by TC-scanning across the cleavage sites of each protease. The results showed that FlAsH/TC inhibited protease cleavage only within limited ranges of the cleavage sites that varied from about 1 to 6 residues-wide depending on the protease, providing an estimate of the PrP residues interacting with each protease. TC-scanning was also used to probe a different type of protein-protein interaction, the conformational conversion of FlAsH-PrPsen to the prion disease-associated isoform, PrPres. PrP constructs with FlAsH/TC insertions at residues 90–96 but not 97–101 were converted to FlAsH-PrPres, identifying a boundary separating loosely versus compactly folded regions of PrPres. Our observations demonstrate that TC-scanning with the FlAsH/TC tag can be a versatile method for probing protein-protein interactions and folding processes. PMID:23943295

  12. Understanding Mixed Emotions: Paradigms and Measures

    Science.gov (United States)

    Kreibig, Sylvia D.; Gross, James J.

    2017-01-01

    In this review, we examine the paradigms and measures available for experimentally studying mixed emotions in the laboratory. For eliciting mixed emotions, we describe a mixed emotions film library that allows for the repeated elicitation of a specific homogeneous mixed emotional state and appropriately matched pure positive, pure negative, and neutral emotional states. For assessing mixed emotions, we consider subjective and objective measures that fall into univariate, bivariate, and multivariate measurement categories. As paradigms and measures for objectively studying mixed emotions are still in their early stages, we conclude by outlining future directions that focus on the reliability, temporal dynamics, and response coherence of mixed emotions paradigms and measures. This research will build a strong foundation for future studies and significantly advance our understanding of mixed emotions. PMID:28804752

  13. A New Paradigm for Chemical Engineering?

    DEFF Research Database (Denmark)

    Gani, Rafiqul

    evidence of this change comes from the jobs taken by graduating chemical engineering professionals in North America, Europe, and some of the Asian countries. In terms of where the graduating chemical engineers are going to work, a clear shift from the commodity chemical industry to the product oriented...... businesses has been observed. There is an increasing trend within the chemical industry to focus on products and the sustainable processes that can make them. Do these changes point to a paradigm shift in chemical engineering as a discipline? Historically, two previous paradigm shifts in chemical engineering...... corresponded to major shifts in chemical engineering as a discipline, which affected not only the education of chemical engineers, but also the development of chemical engineering as a discipline. Has the time come for a new paradigm shift that will prepare the current and future chemical engineering graduates...

  14. Golkar Party's Political Communications the New Paradigm Bakrie Leadership 2009-2013

    Directory of Open Access Journals (Sweden)

    Khoiruddin Muchtar

    2013-11-01

    Full Text Available This study base on the efforts of the Golkar Party's to the process of interpretation, socialization, and implementation of the new paradigm, the paradigm guide to reformations Golkar Party's become to democratic, independent, solid, strong, foundamental, and responsive. How Golkar party's political communication about socialization and implementation of a new paradigm of Golkar Party's leadership Aburizal Bakrie-year period from 2009 to 2012.The aim of this research is to study and overview of the process of socialization and implementation new paradigm Golkar Party's of the Aburizal Bakrie’s leadership. This contect described to using constructivist paradigm through the theory of Performance of Communication and Structuration. Research using the case study method. Data obtained by participation observer, unstructured interviews, and documentary study. The data also collected from informants. The results of this research show: 1 The Golkar Party's has a very significant infrastructure, so the making easier to socialization new paradigm to internal party, but Golkar Party's can not erase stigma society as the New Order party. Socializing new paradigm Golkar Party's to be done in integrated, systematic and continuous addressed to all cadres of various levels from the center to the village. 2 the new paradigm Golkar Party's ideals as the basis and foundation values stand for the Golkar Party's, the implementation is faced with the reality of the condition of the various political considerations and the interests of power, so it can not shown the Golkar Party's political communication with the direction of the reality, Golkar Party's must be have to political communication with the role of multi faces.

  15. A novel Gerstmann-Sträussler-Scheinker disease mutation defines a precursor for amyloidogenic 8 kDa PrP fragments and reveals N-terminal structural changes shared by other GSS alleles

    Science.gov (United States)

    Mercer, Robert C. C.; Fu, Ze-Lin; Mays, Charles E.; Gapeshina, Hristina; Wohlgemuth, Serene L.; Acevedo-Morantes, Claudia Y.; Cashman, Neil R.; Coulthart, Michael B.; Jansen, Gerard H.; Stepanova, Maria

    2018-01-01

    To explore pathogenesis in a young Gerstmann-Sträussler-Scheinker Disease (GSS) patient, the corresponding mutation, an eight-residue duplication in the hydrophobic region (HR), was inserted into the wild type mouse PrP gene. Transgenic (Tg) mouse lines expressing this mutation (Tg.HRdup) developed spontaneous neurologic syndromes and brain extracts hastened disease in low-expressor Tg.HRdup mice, suggesting de novo formation of prions. While Tg.HRdup mice exhibited spongiform change, PrP aggregates and the anticipated GSS hallmark of a proteinase K (PK)-resistant 8 kDa fragment deriving from the center of PrP, the LGGLGGYV insertion also imparted alterations in PrP's unstructured N-terminus, resulting in a 16 kDa species following thermolysin exposure. This species comprises a plausible precursor to the 8 kDa PK-resistant fragment and its detection in adolescent Tg.HRdup mice suggests that an early start to accumulation could account for early disease of the index case. A 16 kDa thermolysin-resistant signature was also found in GSS patients with P102L, A117V, H187R and F198S alleles and has coordinates similar to GSS stop codon mutations. Our data suggest a novel shared pathway of GSS pathogenesis that is fundamentally distinct from that producing structural alterations in the C-terminus of PrP, as observed in other prion diseases such as Creutzfeldt-Jakob Disease and scrapie. PMID:29338055

  16. A radical paradigm shift for a new definition of architecture

    Directory of Open Access Journals (Sweden)

    Alessio Erioli

    2015-11-01

    Full Text Available Architecture is facing a period of great challenges and possibilities, typical of all crises. In such periods, the paradigms we have taken for granted so far are the same ones that generated the crisis, therefore they should undergo a critical revision and new modes of thought and operation (driven by computation can be actively explored and pursued. Instead of retreating to intellectual “safe houses”, architecture should open itself up to and be restructured by the accelerated pace of change imposed by reality, renouncing obsolete methods of anticipating and exerting control and welcoming a more proactive behaviour. It is therefore of primary importance to promote the exercise of projective imagination.

  17. Lab-oriented radical innovations as drivers of paradigm shifts in science

    NARCIS (Netherlands)

    Coccia, M.

    2014-01-01

    An interesting problem in the economics of innovation and strategic management of labs is to explain the drivers of breakthroughs and paradigm shifts in science. This study confronts the issue by analysing a main case study: the technological determinant of the discovery of quasi-periodic materials

  18. Shifting Paradigms in Music Education Research (1953-1978): A Theoretical and Quantitative Reassessment

    Science.gov (United States)

    Jorgensen, Estelle R.; Ward-Steinman, Patrice Madura

    2015-01-01

    The purpose of this study was to examine evidence of a hypothesized shift in the operative research paradigms in music education during the first quarter century of the publication of the "Journal of Research in Music Education," during the period 1953 to 1978. This shift was from humanities-oriented historical and philosophical studies…

  19. Prion Protein Does Not Confer Resistance to Hippocampus-Derived Zpl Cells against the Toxic Effects of Cu2+, Mn2+, Zn2+ and Co2+ Not Supporting a General Protective Role for PrP in Transition Metal Induced Toxicity.

    Science.gov (United States)

    Cingaram, Pradeep Kumar Reddy; Nyeste, Antal; Dondapati, Divya Teja; Fodor, Elfrieda; Welker, Ervin

    2015-01-01

    The interactions of transition metals with the prion protein (PrP) are well-documented and characterized, however, there is no consensus on their role in either the physiology of PrP or PrP-related neurodegenerative disorders. PrP has been reported to protect cells from the toxic stimuli of metals. By employing a cell viability assay, we examined the effects of various concentrations of Cu2+, Zn2+, Mn2+, and Co2+ on Zpl (Prnp-/-) and ZW (Prnp+/+) hippocampus-derived mouse neuronal cells. Prnp-/- Zpl cells were more sensitive to all four metals than PrP-expressing Zw cells. However, when we introduced PrP or only the empty vector into Zpl cells, we could not discern any protective effect associated with the presence of PrP. This observation was further corroborated when assessing the toxic effect of metals by propidium-iodide staining and fluorescence activated cell sorting analysis. Thus, our results on this mouse cell culture model do not seem to support a strong protective role for PrP against transition metal toxicity and also emphasize the necessity of extreme care when comparing cells derived from PrP knock-out and wild type mice.

  20. School on Cloud: Towards a Paradigm Shift

    Science.gov (United States)

    Koutsopoulos, Kostis C.; Kotsanis, Yannis C.

    2014-01-01

    This paper presents the basic concept of the EU Network School on Cloud: Namely, that present conditions require a new teaching and learning paradigm based on the integrated dimension of education, when considering the use of cloud computing. In other words, it is suggested that there is a need for an integrated approach which is simultaneously…

  1. Den postmoderna stadens två paradigm

    DEFF Research Database (Denmark)

    Nielsen, Tom

    2005-01-01

    the attention of politicians, planners and architects today is focused on the individual, not the collective. But the policy of the third way has no counterpart in an urbanism torn between two paradigms. Tom Nielsen paints the picture of what has to urban development since the welfare state...

  2. Redesigning Higher Education: Embracing a New Paradigm

    Science.gov (United States)

    Watson, William R.; Watson, Sunnie Lee

    2014-01-01

    Higher education is under enormous pressure to transform itself and embrace a new paradigm. Operating under an outdated model that no longer aligns with the realities of modern society, institutions of higher education are recognizing the need to drastically remake themselves or possibly cease to exist. This article explores the current landscape…

  3. A postfoundationalist research paradigm of practical theology

    Directory of Open Access Journals (Sweden)

    Sung Kyu Park

    2010-10-01

    This article examines and argues for postfoundationalism – transversal reason, interdisciplinarity and interpreted experience – as a viable theological option against rigid foundationalism and relativistic nonfoundationalism. Also discussed are the process and the interdisciplinary nature of practical theology. It is suggested that narrative research and social constructionism should be part of the research paradigm of postfoundational practical theology.

  4. New Paradigms for Computer Aids to Invention.

    Science.gov (United States)

    Langston, M. Diane

    Many people are interested in computer aids to rhetorical invention and want to know how to evaluate an invention aid, what the criteria are for a good one, and how to assess the trade-offs involved in buying one product or another. The frame of reference for this evaluation is an "old paradigm," which treats the computer as if it were…

  5. Diet and Cancer: The Fourth Paradigm

    Science.gov (United States)

    Walter C. Willett, MD, DrPH, an international expert in diet and nutrition, with posts as a Professor of Epidemiology and Nutrition and Chairman of the Department of Nutrition at Harvard School of Public Health and as Professor of Medicine at Harvard Medical School, presented "Diet and Cancer: The Fourth Paradigm".

  6. Challenging paradigms in estuarine ecology and management

    Science.gov (United States)

    Elliott, M.; Whitfield, A. K.

    2011-10-01

    For many years, estuarine science has been the 'poor relation' in aquatic research - freshwater scientists ignored estuaries as they tended to get confused by salt and tides, and marine scientists were more preoccupied by large open systems. Estuaries were merely regarded by each group as either river mouths or sea inlets respectively. For the past four decades, however, estuaries (and other transitional waters) have been regarded as being ecosystems in their own right. Although often not termed as such, this has led to paradigms being generated to summarise estuarine structure and functioning and which relate to both the natural science and management of these systems. This paper defines, details and affirms these paradigms that can be grouped into those covering firstly the science (definitions, scales, linkages, productivity, tolerances and variability) and secondly the management (pressures, valuation, health and services) of estuaries. The more 'science' orientated paradigms incorporate the development and types of ecotones, the nature of stressed and variable systems (with specific reference to resilience and redundancy), the relationship between generalists and specialists produced by environmental tolerance, the relevance of scale in relation to functioning and connectivity, the sources of production and degree of productivity, the biodiversity-ecosystem functioning and the stress-subsidy debates. The more 'management' targeted paradigms include the development and effects of exogenic unmanaged pressures and endogenic managed pressures, the perception of health and the ability to manage estuaries (related to internal and external influences), and the influence of all of these on the production of ecosystem services and societal benefits.

  7. THE NEW PUBLIC ADMINISTRATION PARADIGM DIRECTIONS

    OpenAIRE

    CHERVYAKOVA OLHA VOLODYMYRIVNA

    2017-01-01

    This article presents aspects of public administration paradigm of using disciplinary matrix, a public management model based on a feedback mechanism in the subject-subject interaction, which is the basis of theoretical and methodological establishment in public administration science (Public administration) in Ukraine.

  8. 06472 Abstracts Collection - XQuery Implementation Paradigms

    NARCIS (Netherlands)

    Boncz, Peter A.; Grust, Torsten; Siméon, Jerome; Boncz, P.A.; Grust, T.; Siméon, J.; van Keulen, Maurice

    From 19.11.2006 to 22.11.2006, the Dagstuhl Seminar 06472 ``XQuery Implementation Paradigms'' was held in the International Conference and Research Center (IBFI), Schloss Dagstuhl. During the seminar, several participants presented their current research, and ongoing work and open problems were

  9. Answer Set Programming and Other Computing Paradigms

    Science.gov (United States)

    Meng, Yunsong

    2013-01-01

    Answer Set Programming (ASP) is one of the most prominent and successful knowledge representation paradigms. The success of ASP is due to its expressive non-monotonic modeling language and its efficient computational methods originating from building propositional satisfiability solvers. The wide adoption of ASP has motivated several extensions to…

  10. Toward an Ecological Paradigm in Adventure Programming

    Science.gov (United States)

    Beringer, Almut

    2004-01-01

    Many forms of adventure therapy, in particular wilderness therapy, rely on challenges in the outdoors to achieve objectives of client change. While nature is drawn on as a medium for therapy and healing, some adventure therapists give nature little if any mention when it comes to explaining therapeutic success. The dominant paradigm in psychology…

  11. ACCOUNTING PARADIGMS WHICH FAVOR HISTORICAL COST

    Directory of Open Access Journals (Sweden)

    Valentin Gabriel CRISTEA

    2014-05-01

    Full Text Available Henning Kirkegaard shows that the evolution of accounting is to shift from one paradigm to another . Business continuity perspective should guide the company into the future , without confine it exclusively in the past. Accounting in its classical form , however, can not be dissociated from the historical cost evaluation .

  12. On the solitary wave paradigm for tsunamis

    DEFF Research Database (Denmark)

    Madsen, Per A.; Fuhrman, David R.; Schäffer, Hemming Andreas

    2008-01-01

    Since the 1970s, solitary waves have commonly been used to model tsunamis especially in experimental and mathematical studies. Unfortunately, the link to geophysical scales is not well established, and in this work we question the geophysical relevance of this paradigm. In part 1, we simulate...

  13. Evolving conservation paradigms for the Anthropocene

    Science.gov (United States)

    Ariel E. Lugo

    2014-01-01

    The Anthropocene will have fundamental effects on the species composition, function, and structure of the ecosystems of the world. Land management agencies such as the USDA Forest Service will need to adapt their policies and conservation activities to avoid engaging in continuous conflict with natural processes and unfamiliar biotic assemblages. Conservation paradigms...

  14. A new paradigm for doing Reformed dogmatics

    Directory of Open Access Journals (Sweden)

    G. J. Spykman

    1992-06-01

    Full Text Available When discussing Reformational Theology: A New Paradigm for Doing Dogmatics some people may call it my opus magnum. Perhaps time 'will tell. The book has only recently - early 1992 - entered the marketplace of theological ideas. How critic readers and reviewers respond will go a long way toward settling the case.

  15. Moral Developmental Science between Changing Paradigms

    Science.gov (United States)

    Keller, Monika

    2012-01-01

    This review encompasses a time-span of about 50 years of research on morality and moral development. It discusses Kohlberg's (1984) work as a milestone that constituted the cognitive developmental viewpoint of morality and that dominated research for about three decades. In this paradigm the role of reasoning and deliberation was emphasized as the…

  16. Paradigms of Interaction Between Culture and Politics

    Directory of Open Access Journals (Sweden)

    Morteza Bahrani

    2012-12-01

    Full Text Available Political thought as a normative knowledge seeks a good society and the means for its realization. Accordingly, every intellectual paradigm introduces us a social and individual situation which is the best. This model, itself requires a dramatic change in the culture and flourishes it. In another words, there is a necessary relationship between the elements of political thought and the culture in every society. This relationship is twofold, so it is impossible to indicate whether which aspect is the first. So every paradigm feeds some special elements into the current culture of society, while there is it feedback. It is important that political thought goes in search of condition for cultural flourishing which is according whit the criteria of good society. This paper focuses on most important paradigm in political thought history and shows the trend in which indicates the relationships between political thought and culture. This trend looks at human beings as "citizen", then "the individual"; and in the modem era, paradigms of "critical modem", "postmodern", and "communitarian" has a key role in prospering the realm of culture.

  17. Fourth Generation War: Paradigm for Change

    Science.gov (United States)

    2005-06-01

    PARADIGM FOR CHANGE by Ghanshyam Singh Katoch June 2005 Thesis Advisor : Kalev Sepp Second Reader...Approved by: Kalev Sepp Thesis Advisor Douglas Borer Second Reader Gordon McCormick Chairman, Department of Defense...combination of all the resources of the government, not just the army. d. Economy of Effort A Robo -Soldier is a small, tracked, electrically powered vehicle

  18. Operationalizing Social Justice Counseling: Paradigm to Practice

    Science.gov (United States)

    Lewis, Judith A.

    2011-01-01

    Social justice counseling, like all humanistic models, recognizes the dignity of each human being, affirms the right of all people to choose and work toward their own goals, and asserts the importance of service to community. The social justice paradigm brings a special emphasis on the role of the environment. (Contains 1 figure and 1 table.)

  19. SCIENTIFIC PARADIGM SHIFT AS THE BACKGROUND OF LANGUAGE EDUCATION

    Directory of Open Access Journals (Sweden)

    V. D. Tabanakova

    2017-01-01

    Full Text Available Introduction. Recently, there has been a cardinal restructuring of university preparation. Linguistic education takes up nearly the last position in the new model of the higher school dictated by economic interests. Investments in linguistic projects are considered as unprofitable today. The linguistic component in educational programs of a bachelor degree is reduced to a minimum, and focused on language knowledge promoting as communication technologies.The aim of the work purposes to trace how the scientific and the linguistic paradigm shift have an impact on the domestic linguistic education system, and to show the unrealized potential capacity of linguistic knowledge.Methodology and research methods. The methodology of the offered research is based, on the one hand, upon the domestic periodical press review on the linguistic education problems for the last 15 years, on the other – on the philosophical analysis of science historical forms which change has caused the past, the present and the future of linguistics and linguistic education. The inductive methods to integrate different approaches are also used.Theoretical significance. The author emphasizes the need to consider the problems of higher education in philosophical aspect, through the interaction of a scientific and educational paradigm.Results and scientific novelty. At a time of global changes in domestic higher education the linguistic education is considered to be a display of the convergence process of natural sciences, technology and humanities. The philosophical study of the scientific paradigms – classical, non-classical and post-non-classical has revealed the regularities of the linguistic scientific paradigms – structural, communicative and cognitive. Each of the paradigms was traced in the frame of linguistic education functions alternation and constantly changing academic programs.A new take on the U-turn of a centrifugal vector in science has obviously demonstrated

  20. The membrane paradigm for black holes

    International Nuclear Information System (INIS)

    Price, R.H.; Thorne, K.S.

    1988-01-01

    It is now widely accepted that black holes exist and have an astrophysical role, in particular as the likely power source of quasars. To understand this role with ease, the authors and their colleagues have developed a new paradigm for black holes - a new way to picture, think about and describe them. As far as possible it treats black holes as ordinary astrophysical objects, made of real material. A black hole in this description is a spherical or oblate surface made of a thin, electrically conducting membrane. It was the author's quest to understand the Blandford-Znajek process intuitively that led them to create the membrane paradigm. Their strategy was to translate the general-relativistic mathematics of black holes into the same language of three-dimensional space that is used for magnetized plasmas and to create a new set of black-hole diagrams and pictures to go along with the language. 9 figs

  1. Changing the Dominant Paradigm in Economics

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Mollo

    2015-10-01

    Full Text Available This article addresses the discussion proposed by the World Academy of Art & Science (WAAS about the need to build a new paradigm to confront the challenges of the global society and to move across to a New Society discussing specific problems related to economic globalization and proposing changes. The ways in which economic orthodoxy and heterodoxy analyze the role of the State and the question of sustainability of development and the problems of environmental sustainability depend on their different views or theoretical arguments about the role of the market. The article contrasts the mainstream economics arguments to support the free market context of globalization with Post-Keynesian and Marxist’s skeptical or critical views. Finally, it proposes some strategies to face the critical aspects analyzed making suggestions to move to another dominant economic paradigm.

  2. [Assistance to the climacteric woman: new paradigms].

    Science.gov (United States)

    Lorenzi, Dino Roberto Soares De; Catan, Lenita Binelli; Moreira, Karen; Artico, Graziela Rech

    2009-01-01

    Population aging is a demographic reality for Brazil. Consequently, in the next years it is expected a progressive increase in seeking health care services in the country by women with complaints related to climacterium. Parallel to it, assistance at this part of woman's life has been going through a paradigm shift which has imposed to health professionals a change of attitude in relation to this stage of woman's life. Today it is acknowledged that the climacterium is influenced by biological, psychosocial and cultural factors, whose knowledge is fundamental for planning a more qualified and humanized care. This article proposes a reflection on the paradigm shifts in assistance at climacterium, highlighting important aspects as multidisciplinarity and interdisciplinarity, so as to serve better this portion of population, and provide it with more integrated and individualized care, bringing together knowledge and sensitivity, and always aiming at a better quality of life.

  3. Inhabiting compassion: A pastoral theological paradigm

    Directory of Open Access Journals (Sweden)

    Phil C. Zylla

    2017-08-01

    Full Text Available Inspired by the vision of care in Vincent van Gogh’s depiction of the parable of the Good Samaritan, this article offers a paradigm for inhabiting compassion. Compassion is understood in this article as a moral emotion that is also a pathocentric virtue. This definition creates a dynamic view of compassion as a desire to alleviate the suffering of others, the capacity to act on behalf of others and a commitment to sustain engagement with the suffering other. To weave this vision of compassion as a habitus rather than a theoretical construct, the article develops three phases of compassion: seeing, companioning and sighing. This framework deepens and augments a pastoral theological paradigm of compassion with the aim of inculcating an inhabited compassion in caregivers and the communities in which they participate.

  4. BMS invariance and the membrane paradigm

    International Nuclear Information System (INIS)

    Penna, Robert F.

    2016-01-01

    The Bondi-van der Burg-Metzner-Sachs (BMS) group is the asymptotic symmetry group of asymptotically flat spacetime. It is infinite dimensional and entails an infinite number of conservation laws. According to the black hole membrane paradigm, null infinity (in asymptotically flat spacetime) and black hole event horizons behave like fluid membranes. The fluid dynamics of the membrane is governed by an infinite set of symmetries and conservation laws. Our main result is to point out that the infinite set of symmetries and conserved charges of the BMS group and the membrane paradigm are the same. This relationship has several consequences. First, it sheds light on the physical interpretation of BMS conservation laws. Second, it generalizes the BMS conservation laws to arbitrary subregions of arbitrary null surfaces. Third, it clarifies the identification of the superrotation subgroup of the BMS group. We briefly comment on the black hole information problem.

  5. Paradigms of modern radio-biology

    International Nuclear Information System (INIS)

    Grodzins'kij, D.M.

    2005-01-01

    The basic paradigms of modern radio-biology are considered as models of pictures of essence of radio-biology problems and methods of their decision. It is marked on absolute heuristics of these ascending conceptual assertions and their assistance to subsequent development of experimental science. That has the concrete display in the decision of actual tasks of protection of people from action of ionizing radiation

  6. The Knowledge Society: A Sustainability Paradigm

    Directory of Open Access Journals (Sweden)

    Naim Hamdija Afgan

    2010-10-01

    Full Text Available This paper defines the knowledge society as a human structured organisation based on contemporary developed knowledge and representing new quality of life support systems. It implies the need for a full understanding of distribution of knowledge, access to information and the capability to transfer information into a knowledge. The understanding of knowledge is the central challenge when defining a knowledge society. From our present perception of knowledge society, it is of interest to emphasize the role of the knowledge society in future development of human society. The life support systems are essential pillars of human society development. In this respect knowledge society represents a new paradigm for future development and it is strongly correlated to sustainable development. For this reason the sustainability paradigm of knowledge society is a potential frame for human society development leading to social cohesion, economic competitiveness and stability, use of resources and economic development, safeguarding biodiversity and the ecosystem.In order to verify the mutual relation between knowledge society and sustainability, we have to introduce the difference between these two terms. The knowledge society is based on the agglomeration of eco-knowledge, env-knowledge and soc-knowledge, it may be evaluated as the complex knowledge of quality of life support systems. We have to introduce metrics which will allow us to present knowledge as the paradigm of the number of indicators for verifying progress made.Sustainability metrics are designed to consolidate measures of economic, environmental and social performance of any system. It can be understood as a pattern for evaluation of the available knowledge about systems and their performance. In particular the decision-making process for the selection of the system under consideration must be based on the available knowledge. The link between knowledge and sustainability makes it possible for

  7. Agricultural Economics and Qualitative Research: Incompatible Paradigms?

    OpenAIRE

    Vera Bitsch

    2000-01-01

    The disciplinary paradigm of agricultural economics emphasizes rational behavior in a world constrained by scarce resources. The research practice focuses on the quantitative modeling of optimization behavior. These models, though, only offer limited support to practitioners in solving real-world problems. Qualitative research approaches contribute to this task, particularly with research in developing countries. Participatory action research was introduced in the seventies; case studies have...

  8. Doing smooth pursuit paradigms in Windows 7

    DEFF Research Database (Denmark)

    Wilms, Inge Linda

    predict strengths or deficits in perception and attention. However, smooth pursuit movements have been difficult to study and very little normative data is available for smooth pursuit performance in children and adults. This poster describes the challenges in setting up a smooth pursuit paradigm...... in Windows 7 with live capturing of eye movements using a Tobii TX300 eye tracker. In particular, the poster describes the challenges and limitations created by the hardware and the software...

  9. Ideomotor compatibility in the psychological refractory period effect: 29 years of oversimplification.

    Science.gov (United States)

    Lien, Mei-Ching; Proctor, Robert W; Allen, Philip A

    2002-04-01

    Four experiments examined whether the psychological refractory period (PRP) effect can be eliminated with ideomotor compatible (IM) but not stimulus-response compatible (SR) tasks, as reported by A. G. Greenwald and H. G. Shulman (1973). Their tasks were used: a left or right movement to a left- or right-pointing arrow (IM) or to the word left or right (SR) for Task 1; saying "A" or "B" (IM) or "1" or "2" (SR) to an auditory A or B for Task 2. The stimulus onset asynchronies were 0, 100, 200, 300, 500, and 1,000 ms in Experiment 1, and only 0, 100, 200, and 1,000 ms in Experiments 2-4. The arrow was in the center of the screen in Experiments 1-3 and to the left or right in Experiment 4. As in Greenwald and Shulman's Experiment 2, the instructions stated that most often the 2 stimuli would be presented simultaneously. A PRP effect was obtained in all conditions, most likely because response-selection decisions are required even for IM tasks.

  10. What Do Ecological Paradigms Offer to Conservation?

    International Nuclear Information System (INIS)

    Ale, S.B.; Howe, H.F.; Ale, S.B.; Howe, H.F.

    2010-01-01

    Ecological theory provides applications to biodiversity management but often falls short of expectations. One possibility is that heuristic theories of a young science are too immature. Logistic growth predicts a carrying capacity, but fisheries managed with the Lotka-Volterra paradigm continue to collapse. A second issue is that general predictions may not be useful. The theory of island biogeography predicts species richness but does not predict community composition. A third possibility is that the theory itself may not have much to do with nature, or that empirical parameterization is too difficult to know. The meta population paradigm is relevant to conservation, but meta populations might not be common in nature. For instance, empirical parameterization within the meta population paradigm is usually infeasible. A challenge is to determine why ecology fails to match needs of managers sometimes but helps at other. Managers may expect too much of paradigmatic blueprints, while ecologists believe them too much. Those who implement biodiversity conservation plans need simple, pragmatic guidelines based on science. Is this possible. What is possible An eclectic review of theory and practice demonstrate the power and weaknesses of the ideas that guide conservation and attempt to identify reasons for prevailing disappointment.

  11. Toward a Metatheoretical Integration of Developmental Paradigms

    Directory of Open Access Journals (Sweden)

    Mark W. Antley

    2010-07-01

    Full Text Available This paper shows how a partial consilience might be achieved in the field of human development by means of principles from general systems theory. The author concurs with Sameroff (1989 that it is possible to interpret the mechanistic, organisimic, and contextualist paradigms/worldviews (Goldhaber, 2000; Pepper, 1970 in terms of general systems theory. The author selects a major developmentalist from each paradigm and interprets that scholar’s work in terms of systems principles. The following developmentalists were selected: Arnold Sameroff (contextualism, Erik Erickson (organicism, and Albert Bandura (mechanism. The systems principles employed are wholeness and order, self-stabilization, self-reorganization, hierarchical interaction, and dialectical contradiction (Sameroff, 1989. The author addresses the conflicting presuppositions of the major paradigms in order to provide for their theoretical subsuming under systems theory. Finally, the author notes areas of inconsistency that will need to be resolved in the future and calls for further scholarship to translate developmental theory in terms of general systems theory for the benefit of students, scholars, consultants and other practitioners familiar with systems theory.

  12. Marketing communications: Qualitative and quantitative paradigm

    Directory of Open Access Journals (Sweden)

    Uzelac Nikola

    2005-01-01

    Full Text Available This paper focuses on key issues in relation to the choice of basic language of communication of marketing as a practical and academic field. Principally, marketing managers prefer descriptive way of expression, but they should use the advantages of language of numbers much more. By doing so, they will advance decision-making process - and the communication with finance and top management. In this regard, models offered by academic community could be helpful. This especially pertains to those positive or normative verbal approaches and models in which mathematics and statistical solutions have been embedded, as well as to those which emphasize financial criteria in decision-making. Concerning the process of creation and verification of scientific knowledge, the choice between languages of words and numbers is the part of much wider dimension, because it is inseparable from the decision on basic research orientation. Quantitative paradigm is more appropriate for hypotheses testing, while qualitative paradigm gives greater contribution in their generation. Competition factor could become the key driver of changes by which existing "parallel worlds" of main paradigms would be integrating, for the sake of disciplinary knowledge advancement.

  13. Playing off the beat: Applying the jazz paradigm to psychotherapy.

    Science.gov (United States)

    Johnson, David Read

    2018-02-01

    A jazz paradigm is applied to traditional psychotherapy practice, illuminating the links between psychotherapy and the Romantic aesthetic tradition, primarily in the centrality of concepts such as attunement. Modernist disruptions of realism during the early 20 th century, such as jazz, elaborated dissonant and improvisational artistic impulses that brought new vitality to their art forms. The psychotherapeutic relationship also has potential avenues for multilevel and discrepant communication that open possibilities of freedom. However, the limitations imposed by the single channel nature of comprehended language, compared with the capacity of artistic media to express multiple sensory information simultaneously, remain the most significant obstacle to dimensionalizing the psychotherapeutic dialogue. Psychotherapy may have much to gain from embracing some of the concepts underlying the jazz aesthetic. © 2018 Wiley Periodicals, Inc.

  14. Paradigm Adherence and Personality Correlates across Mental Health Professions

    Science.gov (United States)

    Rauscher, Laura Anne

    2012-01-01

    Paradigm adherence has been developed as a meta-theoretical approach to organize and to classify the multitude of different theories of counseling and psychotherapy. Four paradigms have been identified in the literature: The Organic-Medical, The Psychological, The Systemic-Relational, and the Social Constructivist paradigms. Only one other study…

  15. Linking aims, paradigm and method in nursing research.

    Science.gov (United States)

    Houghton, Catherine; Hunter, Andrew; Meskell, Pauline

    2012-01-01

    To explore the use of paradigms as ontological and philosophical guides for conducting PhD research. A paradigm can help to bridge the aims of a study and the methods to achieve them. However, choosing a paradigm can be challenging for doctoral researchers: there can be ambiguity about which paradigm is suitable for a particular research question and there is a lack of guidance on how to shape the research process for a chosen paradigm. The authors discuss three paradigms used in PhD nursing research: post-positivism, interpretivism and pragmatism. They compare each paradigm in relation to its ontology, epistemology and methodology, and present three examples of PhD nursing research studies to illustrate how research can be conducted using these paradigms in the context of the research aims and methods. The commonalities and differences between the paradigms and their uses are highlighted. Creativity and flexibility are important when deciding on a paradigm. However, consistency and transparency are also needed to ensure the quality and rigour necessary for conducting nursing research. When choosing a suitable paradigm, the researcher should ensure that the ontology, epistemology and methodology of the paradigm are manifest in the methods and research strategies employed.

  16. The Imperative Paradigm of Korowai, a language of West Papua

    NARCIS (Netherlands)

    de Vries, Lourens; Aikhenvald, Alexandra; Dixon, R.M.W

    2017-01-01

    The imperative paradigm of Korowai, a Papuan language of West Papua, is the richest independent verb paradigm of Korowai: it makes more tense, aspect, mood, person and number distinctions than all other verb paradigms. This formal richness is matched by functional richness: imperatives are used in a

  17. Nuestra experiencia en el tratamiento de úlceras crónicas mediante PRF-Vivostat®: Serie de 10 casos Our experience in the treatment of chronic ulcers by PRP-Vivostat®: Series of 10 cases

    Directory of Open Access Journals (Sweden)

    E. Monclús Fuertes

    2009-06-01

    Full Text Available Pretendemos mostrar nuestra experiencia clínica en el manejo de úlceras crónicas de distinta etiología, mediante tratamiento conservador con gel rico en fibrina autóloga más factores de crecimiento plaquetarios o PRP, experiencia que reafirma los buenos resultados obtenidos en estudios anteriores referentes a Cirugía Plástica, Estética y Reparadora El hecho diferencial de nuestro estudio es el trato de las lesiones única y exclusivamente con PRP, sin otros tratamientos adyuvantes como es habitual en otros estudios acerca de este tema Entre los años 2002 y 2007 tratamos con PRP 10 pacientes con historia de fallo en los tratamientos convencionales, con una edad media de 65.6 años. Se realizaron entre 3 y 5 sesiones por paciente, espaciadas por una semana. El método de obtención elegido fue el sistema VIVOSTAT® (MBA Group. Se realizó un control fotográfico en cada sesión. Realizamos un seguimiento visual de las lesiones (pretratamiento- postratamiento, valorándolas según una modificación de la escala de Valbonesi et al a la que llamamos "Escala de Zaragoza", siendo el resultado pobre en 1 paciente, regular en 2, bueno en 5 y excelente en 2. El uso de PRP para úlceras crónicas en pacientes refractarios a otro tipo de tratamientos, tanto conservadores como quirúrgicos, es actualmente una alternativa real para conseguir una mejoría evidente e incluso la curación completa de las lesiones.The aim of this study is to evaluate our clinical experience in the management of chronic ulcers by conservative treatment with autologous fibrin-rich gel further platelet growth factors or PRP. This experience reaffirms the good results obtained in earlier studies relating to Plastic, Reconstructive and Aesthetic Surgery; moreover, the strength of our study is the use of PRP as the only treatment of such injuries, without other adjuvant treatments as usual in other works on this topic. From 2002 to 2007, we treated with PRP 10 patients with a

  18. Evolution of periodicity in periodical cicadas.

    Science.gov (United States)

    Ito, Hiromu; Kakishima, Satoshi; Uehara, Takashi; Morita, Satoru; Koyama, Takuya; Sota, Teiji; Cooley, John R; Yoshimura, Jin

    2015-09-14

    Periodical cicadas (Magicicada spp.) in the USA are famous for their unique prime-numbered life cycles of 13 and 17 years and their nearly perfectly synchronized mass emergences. Because almost all known species of cicada are non-periodical, periodicity is assumed to be a derived state. A leading hypothesis for the evolution of periodicity in Magicicada implicates the decline in average temperature during glacial periods. During the evolution of periodicity, the determinant of maturation in ancestral cicadas is hypothesized to have switched from size dependence to time (period) dependence. The selection for the prime-numbered cycles should have taken place only after the fixation of periodicity. Here, we build an individual-based model of cicadas under conditions of climatic cooling to explore the fixation of periodicity. In our model, under cold environments, extremely long juvenile stages lead to extremely low adult densities, limiting mating opportunities and favouring the evolution of synchronized emergence. Our results indicate that these changes, which were triggered by glacial cooling, could have led to the fixation of periodicity in the non-periodical ancestors.

  19. Polo-like kinase 3 (PLK3) mediates the clearance of the accumulated PrP mutants transiently expressed in cultured cells and pathogenic PrP(Sc) in prion infected cell line via protein interaction.

    Science.gov (United States)

    Wang, Hui; Tian, Chan; Fan, Xue-Yu; Chen, Li-Na; Lv, Yan; Sun, Jing; Zhao, Yang-Jing; Zhang, Lu-bin; Wang, Jing; Shi, Qi; Gao, Chen; Chen, Cao; Shao, Qi-Xiang; Dong, Xiao-Ping

    2015-05-01

    Polo-like kinases (PLKs) family has long been known to be critical for cell cycle and recent studies have pointed to new dimensions of PLKs function in the nervous system. Our previous study has verified that the levels of PLK3 in the brain are severely downregulated in prion-related diseases. However, the associations of PLKs with prion protein remain unclear. In the present study, we confirmed that PrP protein constitutively interacts with PLK3 as determined by both in vitro and in vivo assays. Both the kinase domain and polo-box domain of PLK3 were proved to bind PrP proteins expressed in mammalian cell lines. Overexpression of PLK3 did not affect the level of wild-type PrP, but significantly decreased the levels of the mutated PrPs in cultured cells. The kinase domain appeared to be responsible for the clearance of abnormally aggregated PrPs, but this function seemed to be independent of its kinase activity. RNA-mediated knockdown of PLK3 obviously aggravated the accumulation of cytosolic PrPs. Moreover, PLK3 overexpression in a scrapie infected cell line caused notable reduce of PrP(Sc) level in a dose-dependent manner, but had minimal effect on the expression of PrP(C) in its normal partner cell line. Our findings here confirmed the molecular interaction between PLK3 and PrP and outlined the regulatory activity of PLK3 on the degradation of abnormal PrPs, even its pathogenic isoform PrP(Sc). We, therefore, assume that the recovery of PLK3 in the early stage of prion infection may be helpful to prevent the toxic accumulation of PrP(Sc) in the brain tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF).

    Science.gov (United States)

    Masuki, Hideo; Okudera, Toshimitsu; Watanebe, Taisuke; Suzuki, Masashi; Nishiyama, Kazuhiko; Okudera, Hajime; Nakata, Koh; Uematsu, Kohya; Su, Chen-Yao; Kawase, Tomoyuki

    2016-12-01

    The development of platelet-rich fibrin (PRF) drastically simplified the preparation procedure of platelet-concentrated biomaterials, such as platelet-rich plasma (PRP), and facilitated their clinical application. PRF's clinical effectiveness has often been demonstrated in pre-clinical and clinical studies; however, it is still controversial whether growth factors are significantly concentrated in PRF preparations to facilitate wound healing and tissue regeneration. To address this matter, we performed a comparative study of growth factor contents in PRP and its derivatives, such as advanced PRF (A-PRF) and concentrated growth factors (CGF). PRP and its derivatives were prepared from the same peripheral blood samples collected from healthy donors. A-PRF and CGF preparations were homogenized and centrifuged to produce extracts. Platelet and white blood cell counts in A-PRF and CGF preparations were determined by subtracting those counts in red blood cell fractions, supernatant acellular serum fractions, and A-PRF/CGF exudate fractions from those counts of whole blood samples. Concentrations of growth factors (TGF-β1, PDGF-BB, VEGF) and pro-inflammatory cytokines (IL-1β, IL-6) were determined using ELISA kits. Compared to PRP preparations, both A-PRF and CGF extracts contained compatible or higher levels of platelets and platelet-derived growth factors. In a cell proliferation assay, both A-PRF and CGF extracts significantly stimulated the proliferation of human periosteal cells without significant reduction at higher doses. These data clearly demonstrate that both A-PRF and CGF preparations contain significant amounts of growth factors capable of stimulating periosteal cell proliferation, suggesting that A-PRF and CGF preparations function not only as a scaffolding material but also as a reservoir to deliver certain growth factors at the site of application.

  1. Identification of seven haplotypes of the caprine PrP gene at codons 127, 142, 154, 211, 222 and 240 in French Alpine and Saanen breeds and their association with classical scrapie.

    Science.gov (United States)

    Barillet, F; Mariat, D; Amigues, Y; Faugeras, R; Caillat, H; Moazami-Goudarzi, K; Rupp, R; Babilliot, J M; Lacroux, C; Lugan, S; Schelcher, F; Chartier, C; Corbière, F; Andréoletti, O; Perrin-Chauvineau, C

    2009-03-01

    In sheep, susceptibility to scrapie is mainly influenced by polymorphisms of the PrP gene. In goats, there are to date few data related to scrapie susceptibility association with PrP gene polymorphisms. In this study, we first investigated PrP gene polymorphisms of the French Alpine and Saanen breeds. Based on PrP gene open reading frame sequencing of artificial insemination bucks (n=404), six encoding mutations were identified at codons 127, 142, 154, 211, 222 and 240. However, only seven haplotypes could be detected: four (GIH(154)RQS, GIRQ(211)QS, GIRRK(222)S and GIRRQP(240)) derived from the wild-type allele (G(127)I(142)R(154)R(211)Q(222)S(240)) by a single-codon mutation, and two (S(127)IRRQP(240) and GM(142)RRQP(240)) by a double-codon mutation. A case-control study was then implemented in a highly affected Alpine and Saanen breed herd (90 cases/164 controls). Mutations at codon 142 (I/M), 154 (R/H), 211 (R/Q) and 222 (Q/K) were found to induce a significant degree of protection towards natural scrapie infection. Compared with the baseline homozygote wild-type genotype I(142)R(154)R(211)Q(222)/IRRQ goats, the odds of scrapie cases in IRQ(211)Q/IRRQ and IRRK(222)/IRRQ heterozygous animals were significantly lower [odds ratio (OR)=0.133, PFrench Alpine and Saanen breeds were low (0.5-18.5 %), which prevent us from assessing the influence of all the possible genotypes in natural exposure conditions.

  2. GHRH, PRP-PACAP and GHRHR Target Sequencing via an Ion Torrent Personal Genome Machine Reveals an Association with Growth in Orange-Spotted Grouper (Epinephelus coioides

    Directory of Open Access Journals (Sweden)

    Liang Guo

    2015-11-01

    Full Text Available Growth hormone-releasing hormone (GHRH and the receptor, GHRHR, constitute important components of the hypothalamus-pituitary growth axis and act on the downstream growth hormone (GH. PACAP-related peptide/pituitary adenylate cyclase activating polypeptide (PRP-PACAP is a paralog of GHRH. These genes all play key roles in development and growth patterns. To improve the quality of cultured fish strains, natural genetic variation must be examined and understood. A mixed linear model has been widely used in association mapping, taking the population structures and pairwise kinship patterns into consideration. In this study, a mass cross population of orange-spotted grouper (Epinephelus coioides was examined. These candidate genes were found to harbor low nucleotide diversity (θw from 0.00154 to 0.00388 and linkage disequilibrium levels (delay of 50% within 2 kbp. Association mapping was employed, and two single-nucleotide polymorphisms (KR269823.1:g.475A>C and KR269823.1:g.2143T>C were found to be associated with growth (false discovery rate Q < 0.05, explaining 9.0%–17.0% of the phenotypic variance. The association of KR269823.1:g.2143T>C was also found via haplotype-based association (p < 0.05. The identified associations offer new insights into gene functions, and the associated single-nucleotide polymorphisms (SNPs may be used for breeding purposes.

  3. Effects of in vivo applications of peripheral blood-derived mesenchymal stromal cells (PB-MSCs) and platlet-rich plasma (PRP) on experimentally injured deep digital flexor tendons of sheep.

    Science.gov (United States)

    Martinello, Tiziana; Bronzini, Ilaria; Perazzi, Anna; Testoni, Stefania; De Benedictis, Gulia Maria; Negro, Alessandro; Caporale, Giovanni; Mascarello, Francesco; Iacopetti, Ilaria; Patruno, Marco

    2013-02-01

    Tendon injuries, degenerative tendinopathies, and overuse tendinitis are common in races horses. Novel therapies aim to restore tendon functionality by means of cell-based therapy, growth factor delivery, and tissue engineering approaches. This study examined the use of autologous mesenchymal stromal cells derived from peripheral blood (PB-MSCs), platelet-rich plasma (PRP) and a combination of both for ameliorating experimental lesions on deep digital flexor tendons (DDFT) of Bergamasca sheep. In particular, testing the combination of blood-derived MSCs and PRP in an experimental animal model represents one of the few studies exploring a putative synergistic action of these treatments. Effectiveness of treatments was evaluated at 30 and 120 days comparing clinical, ultrasonographic, and histological features together with immunohistochemical expression of collagen types 1 and 3, and cartilage oligomeric matrix protein (COMP). Significant differences were found between treated groups and their corresponding controls (placebo) regarding tendon morphology and extracellular matrix (ECM) composition. However, our results indicate that the combined use of PRP and MSCs did not produce an additive or synergistic regenerative response and highlighted the predominant effect of MSCs on tendon healing, enhanced tissue remodeling and improved structural organization. Copyright © 2012 Orthopaedic Research Society.

  4. Paradigm Shift in Language Teaching and Language Teacher Education

    Directory of Open Access Journals (Sweden)

    Elaine Ferreira do Vale Borges

    2014-11-01

    Full Text Available In this article, I intend to conduct a short literature review and discussion about paradigm shift in language teaching and language teacher education from Cartesian to the complexity paradigm. For that, I use the Kuhnian notion of scientific revolution to present a short compilation of works related to paradigm shift in different sciences, including psychology, linguistics and, more emphatically, applied linguistics. The main proposal is to show the evolutions of paradigm shift in language and social sciences and its impact on the emergence of the complexity paradigm in language teaching and language teacher education fields.

  5. SCHOOL ECONOMY IN THE INVENTING EDUCATION PARADIGM

    Directory of Open Access Journals (Sweden)

    Anatoliy Alexandrovich Lepeshev

    2018-01-01

    Full Text Available Requirements applied to specialists for working in the sixth wave of innovation, i.e. Industry 4.0, determines the necessity of education system improvement concerning training solution and, as a result, creation of inventive ideas. Today in our country this process is stimulated by various competitions, including financing for the implementation of results. In training programs knowledge approach still prevails. The corresponding methods, along with stimulation, are included into educational programs in leading foreign educational institutions, mostly at universities. If in previous decades mostly divergent methods were studied (morphological analysis, the focal objects method, synectics, etc., then now the leading place is taken by theory of inventive problem solving – TRIZ created in the former USSR by G.S. Altshuller in connection with the increasing leading corporations requirement for specialists in TRIZ. This fact gives Russia essential competitive advantages in the innovative way of development. For effective use of this advantage it is important to form the TRIZ-based innovative thinking beginning from school days. For this purpose authors developed new methods in TRIZ-pedagogics, uniting metasubject results (in higher education institutions – competences into the system of innovative thinking. As a result, both educational and economic effects are achieved: the intellectual property created in educational process. For schools it is the possibility of significant improvement of financing causing importance of new mechanisms of intellectual property fixation, protection and implementation. Recommendations about creation of such system are provided in the article. Purpose Defining the opportunities and ways of improving economic effectiveness of educational activities in the paradigm of inventive education. Tasks: – analysis of school education institutions experience in implementation of approaches preceding the inventing education

  6. Urgency of changing paradigms in radiation hygiene

    International Nuclear Information System (INIS)

    Kudritskij, Yu.K.; Karpov, V.I.; Georgievskij, A.B.

    1991-01-01

    A problem has been raised on the necessity to substitute the linear-nonthreshold hypothesis as a paradigm of radiation hygiene for the hypothesis of the biological effectiveness of ionizing irradiations. A comparison of the methodological substantiation for both hypotheses and a conception of 'acceptable risk' has been carried out. It is suggested that the possibility of theoretical substantiation of safety standards for the radiational factor on the basis of adatational hypothesis be acknowledged instead of the linear - nonthreshold conception which has lost its historic significance

  7. Causal hydrodynamics and the membrane paradigm

    International Nuclear Information System (INIS)

    Natsuume, Makoto

    2008-01-01

    We obtain the relaxation time for the shear viscous stress for various geometries using the 'membrane paradigm' formula proposed recently. We consider the generic Schwarzschild-anti-de Sitter black holes (SAdS), the generic Dp-brane, the Klebanov-Tseytlin (KT) geometry, and the N=2* theory. The formula is the 'shear mode' result and is not fully trustable, but it may be helpful to learn some generic behaviors about the relaxation time. For example, a simple formula summarizes all known results for SAdS, and a single expression summarizes the results for the Dp-brane and the KT geometry.

  8. In search of a new paradigm

    DEFF Research Database (Denmark)

    Poulsen, Lars K.

    2005-01-01

    In this review of research priorities, presented for the European Commission, food allergy is established as a disease with a considerable impact on modern society. Research paradigms have changed from establishing basic symptomatology and diagnostic methods over allergen characterization to a risk...... mechanisms in the cross-field between immunology and gastroenterology. Research priorities should include the molecular basis of cross-reactivity, the digestion and maintenance of antigenicity, the genetics of food allergy, and the immune response to food antigens and effects on the gastrointestinal immune...

  9. Three paradigms for the analysis of corruption

    Directory of Open Access Journals (Sweden)

    Alberto Vannucci

    2015-10-01

    Full Text Available In the last decades a growing awareness emerged of the relevance of corruption as an hidden factor which may negatively affect political and economic decision-making processes. In spite of a lively scientific debate there is no general consensus on a commonly accepted definition of what corruption is.The A. distinguishes three main paradigms, focusing on different (though not irreconcilable variables.The first is the economic paradigm, which usually takes the principal-agent model of corruption as its founding pillar. In this paradigm corruption is considered the outcome of rational individual choices, and its spread within a certain organization is influenced by the factors defining the structure of expected costs and rewards.A second approach – the cultural paradigm – looks at the differences in cultural traditions, social norms and interiorized values which shape individuals’ moral preferences and consideration of his social and institutional role. These are a leading forces that can push a corrupt public or private agent (not to violate legal norms.A third neo-institutional approach considers also mechanisms which allow the internal regulation of social interactions within corrupt networks, and their effects on individuals’ beliefs and preferences. Though the corrupt agreements cannot be enforced with legal sanctions, several informal, non-written rules, contractual provisos and conventions may regulate the corrupt exchange between agent and corruptor.The A. underlines that corruption is the outcome of a multitude of individual and collective choices which change public opinion towards corruption and its diffusion throughout the state, markets and civil society. There is no univocal recipe to deal with anti-bribery measures, since corruption is a complex and multifaceted phenomenon.Reforms aimed at dismantling systemic corruption have to be finely tuned against its hidden governance structures, i.e. its internal regulation of

  10. Chua's circuit a paradigm for chaos

    CERN Document Server

    1993-01-01

    For uninitiated researchers, engineers, and scientists interested in a quick entry into the subject of chaos, this book offers a timely collection of 55 carefully selected papers covering almost every aspect of this subject. Because Chua's circuit is endowed with virtually every bifurcation phenomena reported in the extensive literature on chaos, and because it is the only chaotic system which can be easily built by a novice, simulated in a personal computer, and tractable mathematically, it has become a paradigm for chaos, and a vehicle for illustrating this ubiquitous phenomenon. Its supreme

  11. Periodization Theory: Confronting an Inconvenient Truth.

    Science.gov (United States)

    Kiely, John

    2018-04-01

    Periodization theory has, over the past seven decades, emerged as the preeminent training planning paradigm. The philosophical underpinnings of periodization theory can be traced back to the integration of diverse shaping influences, whereby coaching beliefs and traditions were blended with historically available scientific insights and contextualized against pervading social planning models. Since then, many dimensions of elite preparation have evolved significantly, as driven by a combination of coaching innovations and science-led advances in training theory, techniques, and technologies. These advances have been incorporated into the fabric of the pre-existing periodization planning framework, yet the philosophical assumptions underpinning periodization remain largely unchallenged and unchanged. One particularly influential academic sphere of study, the science of stress, particularly the work of Hans Selye, is repeatedly cited by theorists as a central pillar upon which periodization theory is founded. A fundamental assumption emanating from the early stress research is that physical stress is primarily a biologically mediated phenomenon: a presumption translated to athletic performance contexts as evidence that mechanical training stress directly regulates the magnitude of subsequent 'fitness' adaptations. Interestingly, however, since periodization theory first emerged, the science of stress has evolved extensively from its historical roots. This raises a fundamental question: if the original scientific platform upon which periodization theory was founded has disintegrated, should we critically re-evaluate conventional perspectives through an updated conceptual lens? Realigning periodization philosophy with contemporary stress theory thus presents us with an opportunity to recalibrate training planning models with both contemporary scientific insight and progressive coaching practice.

  12. Shifting the Climate Finance Paradigm: Nine Key Challenges for Developed Countries

    Energy Technology Data Exchange (ETDEWEB)

    Curtin, Joseph

    2013-03-13

    In 2009, developed countries committed to part-funding the cost of adapting to the impacts of climate change and of low carbon development in developing countries. From 2010 to 2012, fast start finance began to flow from developed country exchequers. However, the climate finance paradigm is now shifting. A transition from loans and grants provided from scarce exchequer resources to innovative instruments for leveraging private capital and mitigating investment risk is required in the coming period. But what are the implications for developed countries? This policy brief explores the policy context defining the current climate finance debate; examines the extent to which commitments have been met; and identifies nine key challenges for developed countries as they enter the new climate finance paradigm, drawing on the lessons of the fast start finance period. This is the second in a series of Environment Nexus policy briefs by leading experts in the fields of agriculture, energy, climate change and water.

  13. Consumers’ Empowerement for a New Marketing Paradigm

    Directory of Open Access Journals (Sweden)

    Victor Danciu

    2013-09-01

    Full Text Available The marketing practices of the companies show that not all of them are observing ethical and moral standards and they manipulate the consumers. This paper has as main goal to examine the most usual unethical techniques, the present status of consumers’ power and how more power could work for a new marketing paradigm. There are many unethical marketing techniques which could be found in deceptive product recipes, packaging, promotion, prices and in other areas. Most consumers have no appropriate powers and tools to counteract the manipulation techniques and feel they have fewer rights than the marketers. The current state of empowerment of the consumer show that the European consumers are not in the best position in the market as the Consumer Empowerment Index proves. This matter of facts emphasizes a strong need for a better empowerment of the consumers. The consumer which has more power and wisely use it could improve the balance of power in the market. But the consumers should have a proactive buying behavior in order to get such results. These revolutionary consumers attack the structural roots of the social, economic and political problems which produces a new market ideology as a part of the new tier of transnational institutional ideology. This consumer behavior may have a strong influence toward a new marketing paradigm.

  14. Osteoporosis: Modern Paradigms for Last Century's Bones.

    Science.gov (United States)

    Kruger, Marlena C; Wolber, Frances M

    2016-06-17

    The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a "brittle bone" disease that occurs in post-menopausal, thin, Caucasian women with low calcium intakes and/or vitamin D insufficiency. However, a study of black women in Africa demonstrated that higher proportions of body fat did not protect bone health. Isoflavone interventions in Asian postmenopausal women have produced inconsistent bone health benefits, due in part to population heterogeneity in enteric bacterial metabolism of daidzein. A comparison of women and men in several Asian countries identified significant differences between countries in the rate of bone health decline, and a high incidence rate of osteoporosis in both sexes. These studies have revealed significant differences in genetic phenotypes, debunking long-held beliefs and leading to new paradigms in study design. Current studies are now being specifically designed to assess genotype differences between Caucasian, Asian, African, and other phenotypes, and exploring alternative methodology to measure bone architecture.

  15. Imaging deductive reasoning and the new paradigm

    Science.gov (United States)

    Oaksford, Mike

    2015-01-01

    There has been a great expansion of research into human reasoning at all of Marr’s explanatory levels. There is a tendency for this work to progress within a level largely ignoring the others which can lead to slippage between levels (Chater et al., 2003). It is argued that recent brain imaging research on deductive reasoning—implementational level—has largely ignored the new paradigm in reasoning—computational level (Over, 2009). Consequently, recent imaging results are reviewed with the focus on how they relate to the new paradigm. The imaging results are drawn primarily from a recent meta-analysis by Prado et al. (2011) but further imaging results are also reviewed where relevant. Three main observations are made. First, the main function of the core brain region identified is most likely elaborative, defeasible reasoning not deductive reasoning. Second, the subtraction methodology and the meta-analytic approach may remove all traces of content specific System 1 processes thought to underpin much human reasoning. Third, interpreting the function of the brain regions activated by a task depends on theories of the function that a task engages. When there are multiple interpretations of that function, interpreting what an active brain region is doing is not clear cut. It is concluded that there is a need to more tightly connect brain activation to function, which could be achieved using formalized computational level models and a parametric variation approach. PMID:25774130

  16. The Institutional Paradigm of Human Capital Development

    Directory of Open Access Journals (Sweden)

    Kolomiiets Viktoriia М.

    2018-03-01

    Full Text Available The formation of the modern conception of human capital is connected with the development of post-industrial information society, knowledge economy and digital economy. The main role in analyzing of the content and role of human capital can play a new institutional economic theory. It is determined that the methodology of research of paradigm change in economic science remains the subject of discussion. The conception of institutional paradigm of human capital development can be attributed to the new economy, the development of which is carried out on the condition that the employee is not always alienated from the relationships of ownership: he himself becomes the owner of the «new» economic resources. The factors of education along with the factors of health care which are determining in the development of human capital are researched. Special attention is paid to education, as it acts as an intellectual capital of the new economy, where knowledge and skills become the «intellectual 5D printer», producing the modern human capital. The transition to a new, post-industrial economy is characterized by a major long-term tendency: the progress of knowledge and the increasing complexity of the socio-economic life; created by powerful factors of information and computer technologies and leading to expansion of global economic space.

  17. Passage of American shad: paradigms and realities

    Science.gov (United States)

    Haro, Alex; Castro-Santos, Theodore

    2012-01-01

    Despite more than 250 years of development, the passage of American shad Alosa sapidissima at dams and other barriers frequently remains problematic. Few improvements in design based on knowledge of the swimming, schooling, and migratory behaviors of American shad have been incorporated into passage structures. Large-scale technical fishways designed for the passage of adult salmonids on the Columbia River have been presumed to have good performance for American shad but have never been rigorously evaluated for this species. Similar but smaller fishway designs on the East Coast frequently have poor performance. Provision of effective downstream passage for both juvenile and postspawning adult American shad has been given little consideration in most passage projects. Ways to attract and guide American shad to both fishway entrances and downstream bypasses remain marginally understood. The historical development of passage structures for American shad has resulted in assumptions and paradigms about American shad behavior and passage that are frequently unsubstantiated by supporting data or appropriate experimentation. We propose that many of these assumptions and paradigms are either unfounded or invalid and that significant improvements to American shad upstream and downstream passage can be made via a sequential program of behavioral experimentation, application of experimental results to the physical and hydraulic design of new structures, and controlled tests of large-scale prototype structures in the laboratory and field.

  18. New paradigms of Game Theory from globalization

    Directory of Open Access Journals (Sweden)

    Francisco Javier Esquivel

    2015-06-01

    Full Text Available Games Theory constitutes a model by means every player tries to predict what they will make the other players in reply to his own actions, and to optimize the result of the above mentioned actions in his benefit knowing that the others are thinking to about the same form. The development of the theory supposed a boom after the World War II, which happened of analyzing exclusively competitive behaviors to considering situations with competitive and cooperative characteristics. Nevertheless, the advance of the humanity and the disappearance of both geopolitical blocks have eliminated the balance of power and have produced the emergence of a world the most based on the exclusive conquest of the power. This has originated the model change and dilemmas, happening from the most cooperative models (Prisoner’s Dilemma or from the models of the Cold War (Dilemma of the Gallina up to reaching the dilemmas of the Leader or of the Hero. This change of paradigm owes to the extension of the globalization, which originates an immeasurable loss of economic, social, political power, of human rights, which they have affected negatively to the poor people. In this paper is studied the change of paradigm caused by the consequences of the globalization and the geopolitical transformations in a monopolar world, analyzing the consequences on the basis of the Theory of Games.

  19. Tolerance of sexual harassment: a laboratory paradigm.

    Science.gov (United States)

    Angelone, David J; Mitchell, Damon; Carola, Kara

    2009-12-01

    The present study attempted to develop a laboratory analogue for the study of tolerance for sexual harassment by using an online speed-dating paradigm. In that context, the relation between participants' sexual harassment attitudes, perpetrator attractiveness, perpetrator status, and perceived dating potential of the perpetrator were examined as factors influencing participants' tolerance of sexually harassing behavior. Participants were 128 female college students from a small northeastern public university. Results indicated that attractiveness, high social status, and attitudinal beliefs about sexual harassment were all predictive of tolerance for sexual harassment, providing preliminary support for the validity of this paradigm. In addition, participants' self reported likelihood to date a bogus male dating candidate was also predictive of tolerance for sexual harassment, over and above the aforementioned variables, suggesting that dating potential can play a role in perceptions of sexual harassment. Further, this experiment demonstrated that perceptions of sexual harassment can be assessed using the in vivo measurement of behavior. In addition, using an online environment not only provides a contemporary spin and adds a greater degree of external validity compared to other sexual harassment analogues, it also reduces any risk of potential physical sexual contact for participants.

  20. Colloidal paradigm in supercapattery electrode systems

    Science.gov (United States)

    Chen, Kunfeng; Xue, Dongfeng

    2018-01-01

    Among decades of development, electrochemical energy storage systems are now sorely in need of a new design paradigm at the nano size and ion level to satisfy the higher energy and power demands. In this review paper, we introduce a new colloidal electrode paradigm for supercapattery that integrates multiple-scale forms of matter, i.e. ion clusters, colloidal ions, and nanosized materials, into one colloid system, coupled with multiple interactions, i.e. electrostatic, van der Waals forces, and chemical bonding, thus leading to the formation of many redox reactive centers. This colloidal electrode not only keeps the original ionic nature in colloidal materials, but also creates a new attribute of high electroactivity. Colloidal supercapattery is a perfect application example of the novel colloidal electrode, leading to higher specific capacitance than traditional electrode materials. The high electroactivity of the colloidal electrode mainly comes from the contribution of exposed reactive centers, owing to the confinement effect of carbon and a binder matrix. Systematic and thorough research on the colloidal system will significantly promote the development of fundamental science and the progress of advanced energy storage technology.

  1. Understanding emerging treatment paradigms in rheumatoid arthritis.

    Science.gov (United States)

    Breedveld, Ferdinand C; Combe, Bernard

    2011-05-25

    Treatment strategies for rheumatoid arthritis (RA) will continue to evolve as new drugs are developed, as new data become available, and as our potential to achieve greater and more consistent outcomes becomes more routine. Many patients will find both symptom relief and modest control of their disease with disease-modifying antirheumatic drugs (DMARDs), yet this course of therapy is clearly not effective in all patients. In fact, despite strong evidence that intensive treatment in the early stages of RA can slow or stop disease progression and may prevent disability, many patients continue to be managed in a stepwise manner and are treated with an ongoing monotherapy regimen with DMARDs. There is now a large body of evidence demonstrating the success of treating RA patients with anti-TNF therapy, usually in combination with methotrexate. As a result of the increased use of anti-TNF therapy, treatment paradigms have changed - and our practice is beginning to reflect this change. In the present review, we summarize the salient points of several recently proposed and emerging treatment paradigms with an emphasis on how these strategies may impact future practice.

  2. A new guiding paradigm for waste disposal

    International Nuclear Information System (INIS)

    Suter, Peter

    2003-01-01

    New situations call for a revision of strategies in the waste recycling and recovery sector. The guiding paradigm is that the evaluation and optimization of strategies ought to be integral, i.e. it ought to incorporate all steps from cradle to grave, all cost components and also to take into account all environmental aspects, as well as resource depletion. Furthermore, all variants of a comparison must have the same output and the same boundaries in space and time. Total cost (comprising also environmental damage and resource depletion) is proposed here as the evaluation function; environmental damage can be made operational by the DALY concept (Hofstetter P. Perspectives in life cycle impact assessment. Boston: Kluwer Academic, 1998) ('disability adjusted loss of life years') accounting for the years of life lost due to premature death, to illness or annoyance. The search for optimal strategies in the waste sector evidently requires the solution of a system with an enormous number of parameters; the method of genetic algorithms may represent a suitable solution paradigm, leading to the result in a reasonable computing time

  3. Tourism development and the degrowth paradigm

    Directory of Open Access Journals (Sweden)

    Andriotis Konstantinos

    2014-01-01

    Full Text Available This paper aims to look at alternatives to the classic models of development by exploring the paradigm of degrowth in a tourism context. Degrowth touted as an alternative to mainstream paradigms of development, aims to ensure a high quality of life for people in a society where work, production and consumption are reduced. As a weapon to the problems accrued by capitalism, degrowth reorients the current unsustainable and inequitable path through the transition to a smaller economy with less production and consumption. By arguing that natural limits to growth of many destinations have already been surpassed and their carrying capacity levels have been reached, degrowth proposes the abandonment of growth which promotes nothing other than a quest for profits on part of the owners of capital and results in disastrous implications for the environment and the humanity. As a philosophical concept and movement, degrowth is revolutionary and anticapitalist directed to sustainable change which results from an interest in locality and place, small and medium-sized enterprises, employment generation and reduction in working hours, ecology and quality of life, decommodification of tourism activity, carbon reduction in transport, changed pattern of production and consumption, and high priority in the travel experience.

  4. Special Feature: Epistemological Paradigms in Evaluation: Implications for Practice. Section 3: "Paradigm Complementarity" Case Studies.

    Science.gov (United States)

    Kamis-Gould, Edna; And Others

    1991-01-01

    Three studies are presented, which illustrate situations in which researchers and funders agreed on the primacy of either the experimental or pragmatic paradigms but acknowledged a role for the other. The studies involved evaluations of mental health care, information systems, and a curriculum for behavioral and academic dysfunction. (SLD)

  5. Paradigm Shift or Business as Usual? Dynamic Complementarities in Innovation Strategies

    OpenAIRE

    James Love; Stephen Roper; Priit Vahter

    2013-01-01

    We investigate claims of a ‘paradigm shift’ towards firms using open innovation as a conscious strategic choice. Such a claim implicitly involves two elements: first, there should be some evidence that firms are increasingly likely to use a combination of internal and external knowledge in their innovation activity, and second, there should evidence that firms derive a systematic advantage from so doing. Using a panel of Irish manufacturing plants over the period 1991-2008 we develop four arc...

  6. Romanian spa tourism: a communist paradigm in a post communist era

    OpenAIRE

    George Erdeli; Ana Irina Dincă; Aurel Gheorghilas; Camelia Surugiu

    2011-01-01

    Spa tourism is one of the oldest forms of tourism which continuously evolved in time as the leisure industry paradigm and the consumers’ behavior changed. Similar to other countries in Central and Eastern Europe, spa tourism is an old phenomenon in Romania which expanded to the dimensions of a well defined tourism industry during the mass tourism period which also corresponded to the communism epoch. Although severely affected by the major political and socio-economic changes which occurred a...

  7. Quantitative analysis of distributed control paradigms of robot swarms

    DEFF Research Database (Denmark)

    Ngo, Trung Dung

    2010-01-01

    describe the physical and simulated robots, experiment scenario, and experiment setup. Third, we present our robot controllers based on behaviour based and neural network based paradigms. Fourth, we graphically show their experiment results and quantitatively analyse the results in comparison of the two......Given a task of designing controller for mobile robots in swarms, one might wonder which distributed control paradigms should be selected. Until now, paradigms of robot controllers have been within either behaviour based control or neural network based control, which have been recognized as two...... mainstreams of controller design for mobile robots. However, in swarm robotics, it is not clear how to determine control paradigms. In this paper we study the two control paradigms with various experiments of swarm aggregation. First, we introduce the two control paradigms for mobile robots. Second, we...

  8. Information processing as a paradigm for decision making.

    Science.gov (United States)

    Oppenheimer, Daniel M; Kelso, Evan

    2015-01-03

    For decades, the dominant paradigm for studying decision making--the expected utility framework--has been burdened by an increasing number of empirical findings that question its validity as a model of human cognition and behavior. However, as Kuhn (1962) argued in his seminal discussion of paradigm shifts, an old paradigm cannot be abandoned until a new paradigm emerges to replace it. In this article, we argue that the recent shift in researcher attention toward basic cognitive processes that give rise to decision phenomena constitutes the beginning of that replacement paradigm. Models grounded in basic perceptual, attentional, memory, and aggregation processes have begun to proliferate. The development of this new approach closely aligns with Kuhn's notion of paradigm shift, suggesting that this is a particularly generative and revolutionary time to be studying decision science.

  9. Thought Suppression Research Methods: Paradigms, Theories, Methodological Concerns

    Directory of Open Access Journals (Sweden)

    Niczyporuk Aneta

    2016-12-01

    Full Text Available It is hard to provide an unequivocal answer to the question of whether or not thought suppression is effective. Two thought suppression paradigms - the “white bear” paradigm and the think/no-think paradigm - give mixed results. Generally, “white bear” experiments indicate that thought suppression is counterproductive, while experiments in the think/no-think paradigm suggest that it is possible to effectively suppress a thought. There are also alternative methods used to study thought suppression, for instance the directed forgetting paradigm or the Stroop task. In the article, I describe the research methods used to explore thought suppression efficacy. I focus on the “white bear” and the think/no-think paradigms and discuss theories proposed to explain the results obtained. I also consider the internal and external validity of the methods used.

  10. A epidemiologia, os valores e o significado de paradigma Epidemiology, values, and the meaning of paradigm

    Directory of Open Access Journals (Sweden)

    Djalma Agripino de Melo Filho

    1997-10-01

    Full Text Available Recentemente, o emprego do termo paradigma chegou ao âmbito epidemiológico. Este texto analisou criticamente uma classificação de 'paradigmas epidemiológicos', proposta por Almeida-Filho. Inicialmente constatou-se que os valores não foram considerados como elementos fundamentais para a construção dos paradigmas, distanciando-se, assim, da matriz kuhniana. Uma vez que a sistematização procurou unir tendências antitéticas, ela pareceu estar mais próxima da epistéme foucaultiana. Finalmente, considerou-se mais apropriada a utilização do termo hegemonia, em vez de paradigma, para sistematizar períodos epidemiológicos, pois os valores das vertentes estão comprometidos com a particularidade (principalmente classe social.Use of the term paradigm has recently reached the epidemiological milieu. This article provides a critical analysis of a classification of "epidemiological paradigms" as proposed by Almeida-Filho. It was initially ascertained that values were not considered fundamental elements for the construction of paradigms, and that they therefore distanced themselves from the Kuhnian matrix. Systematization sought to unite antithetical tendencies and thus seemed closer to the Foucaltian epistéme. Finally, hegemony was considered a more appropriate term than paradigm for systematizing epidemiological periods, since the values of the different watersheds are committed to particularity (principally social class.

  11. Does Flywheel Paradigm Training Improve Muscle Volume and Force? A Meta-Analysis.

    Science.gov (United States)

    Nuñez Sanchez, Francisco J; Sáez de Villarreal, Eduardo

    2017-11-01

    Núñez Sanchez, FJ and Sáez de Villarreal, E. Does flywheel paradigm training improve muscle volume and force? A meta-analysis. J Strength Cond Res 31(11): 3177-3186, 2017-Several studies have confirmed the efficacy of flywheel paradigm training for improving or benefiting muscle volume and force. A meta-analysis of 13 studies with a total of 18 effect sizes was performed to analyse the role of various factors on the effectiveness of flywheel paradigm training. The following inclusion criteria were employed for the analysis: (a) randomized studies; (b) high validity and reliability instruments; (c) published in a high quality peer-reviewed journal; (d) healthy participants; (e) studies where the eccentric programme were described; and (f) studies where increases in muscle volume and force were measured before and after training. Increases in muscle volume and force were noted through the use of flywheel systems during short periods of training. The increase in muscle mass appears was not influenced by the existence of eccentric overload during the exercise. The increase in force was significantly higher with the existence of eccentric overload during the exercise. The responses identified in this analysis are essential and should be considered by strength and conditioning professionals regarding the most appropriate dose response trends for flywheel paradigm systems to optimize the increase in muscle volume and force.

  12. [The template principle: paradigm of modern genetics].

    Science.gov (United States)

    Inge-Vechtomov, S G

    2013-01-01

    The idea of continuity in living systems, which was initially developed in mid-19th century, reached its peak in 1928 thanks to N.K. Koltsov, who proposed the template principle in chromosome reproduction. The determination of genetic functions of nucleic acids and the advent of molecular genetics led to F. Crick's statement of the central dogma of molecular biology in 1958. This dogma became a contemporary version of the template principle (templates of the first order). The discovery of "protein inheritance" underlay the notion of steric or conformational templates (second order) for reproducing conformation in a number of proteins. The template principle supplemented by this notion claims to be the main paradigm of modern genetics.

  13. TAMU: A New Space Mission Operations Paradigm

    Science.gov (United States)

    Meshkat, Leila; Ruszkowski, James; Haensly, Jean; Pennington, Granvil A.; Hogle, Charles

    2011-01-01

    The Transferable, Adaptable, Modular and Upgradeable (TAMU) Flight Production Process (FPP) is a model-centric System of System (SoS) framework which cuts across multiple organizations and their associated facilities, that are, in the most general case, in geographically diverse locations, to develop the architecture and associated workflow processes for a broad range of mission operations. Further, TAMU FPP envisions the simulation, automatic execution and re-planning of orchestrated workflow processes as they become operational. This paper provides the vision for the TAMU FPP paradigm. This includes a complete, coherent technique, process and tool set that result in an infrastructure that can be used for full lifecycle design and decision making during any flight production process. A flight production process is the process of developing all products that are necessary for flight.

  14. Toxicogenomics: A New Paradigm for Nanotoxicity Evaluation.

    Science.gov (United States)

    Dwivedi, Sourabh; Saquib, Quaiser; Ahmad, Bilal; Ansari, Sabiha M; Azam, Ameer; Musarrat, Javed

    2018-01-01

    The wider applications of nanoparticles (NPs) has evoked a world-wide concern due to their possible risk of toxicity in humans and other organisms. Aggregation and accumulation of NPs into cell leads to their interaction with biological macromolecules including proteins, nucleic acids and cellular organelles, which eventually induce toxicological effects. Application of toxicogenomics to investigate molecular pathway-based toxicological consequences has opened new vistas in nanotoxicology research. Indeed, genomic approaches appeared as a new paradigm in terms of providing information at molecular levels and have been proven to be as a powerful tool for identification and quantification of global shifts in gene expression. Toxicological responses of NPs have been discussed in this chapter with the aim to provide a clear understanding of the molecular mechanism of NPs induced toxicity both in in vivo and in vitro test models.

  15. A new paradigm of modern central banking

    Directory of Open Access Journals (Sweden)

    Aleksandra Szunke

    2013-05-01

    Full Text Available The changes in the modern monetary policy, which took place at the beginning of the twenty-first century, in response to the global financial crisis led to the transformation of the place and the role of central banks. The strategic aim of the central monetary institutions has become preventing financial instability. So far, central banks have defined financial stability as a public good, which took care independently of other monetary purposes (Pyka, 2010. Unconventional monetary policy resulted in changes the global central banking. The aim of the study is to identify a new paradigm of the role and place of the central bank in the financial system and its new responsibilities, aimed at countering financial instability.

  16. The Rational Relevance of the Diffuse Paradigms

    Directory of Open Access Journals (Sweden)

    Marin Dinu

    2006-01-01

    Full Text Available Processes like the globalization consistency and learning about society are screened by diffuse concepts such as those taking the last steps of the industrial civilization and hierarchically ordered world through hegemony. This is why the meaning of globalization is given by deviant trends, like globalism, and the knowledge society is taken for the tools promoted by itself, such as the internet. This does not imply only approximations of meaning but rather the vanity of change, preserving the status quo represented by the pre-global world or the adversity principle. Historicism of paradigm cannot be avoided. Evolvement towards something else, announced by globalization is implacable, and the new ordinating principle, the one of competition, opens the opportunity horizon to global world.

  17. The Rational Relevance of the Diffuse Paradigms

    Directory of Open Access Journals (Sweden)

    Marin Dinu

    2006-03-01

    Full Text Available Processes like the globalization consistency and learning about society are screened by diffuse concepts such as those taking the last steps of the industrial civilization and hierarchically ordered world through hegemony. This is why the meaning of globalization is given by deviant trends, like globalism, and the knowledge society is taken for the tools promoted by itself, such as the internet. This does not imply only approximations of meaning but rather the vanity of change, preserving the status quo represented by the pre-global world or the adversity principle. Historicism of paradigm cannot be avoided. Evolvement towards something else, announced by globalization is implacable, and the new ordinating principle, the one of competition, opens the opportunity horizon to global world

  18. Systems healthcare: a holistic paradigm for tomorrow.

    Science.gov (United States)

    Fiandaca, Massimo S; Mapstone, Mark; Connors, Elenora; Jacobson, Mireille; Monuki, Edwin S; Malik, Shaista; Macciardi, Fabio; Federoff, Howard J

    2017-12-19

    Systems healthcare is a holistic approach to health premised on systems biology and medicine. The approach integrates data from molecules, cells, organs, the individual, families, communities, and the natural and man-made environment. Both extrinsic and intrinsic influences constantly challenge the biological networks associated with wellness. Such influences may dysregulate networks and allow pathobiology to evolve, resulting in early clinical presentation that requires astute assessment and timely intervention for successful mitigation. Herein, we describe the components of relevant biological systems and the nature of progression from at-risk to manifest disease. We illustrate the systems approach by examining two relevant clinical examples: Alzheimer's and cardiovascular diseases. The implications of systems healthcare management are examined through the lens of economics, ethics, policy and the law. Finally, we propose the need to develop new educational paradigms to enhance the training of the health professional in an era of systems medicine.

  19. Wind power, policy learning and paradigm change

    International Nuclear Information System (INIS)

    Szarka, Joseph

    2006-01-01

    The aim of this article is to study how policy learning has led to new understandings of ways to support renewable energies, based on experience in the wind power sector. Drawing on analysis of the literature and informed by field-work in the wind power sector in Denmark, France and the UK, it explores the extent to which policy learning over the medium term has brought us closer to models that integrate economic, environmental and societal desiderata into renewables policy in a manner congruent with the sustainable development aspirations espoused by the European Union and its constituent states. It contributes to policy theory development by arguing in favour of a new policy paradigm that reaches beyond measures to increase production capacity per se to embrace both the institutional dynamics of innovation processes and the fostering of societal engagement in implementation processes

  20. Ubiquitous health in practice: the interreality paradigm.

    Science.gov (United States)

    Gaggioli, Andrea; Raspelli, Simona; Grassi, Alessandra; Pallavicini, Federica; Cipresso, Pietro; Wiederhold, Brenda K; Riva, Giuseppe

    2011-01-01

    In this paper we introduce a new ubiquitous computing paradigm for behavioral health care: "Interreality". Interreality integrates assessment and treatment within a hybrid environment, that creates a bridge between the physical and virtual worlds. Our claim is that bridging virtual experiences (fully controlled by the therapist, used to learn coping skills and emotional regulation) with real experiences (allowing both the identification of any critical stressors and the assessment of what has been learned) using advanced technologies (virtual worlds, advanced sensors and PDA/mobile phones) may improve existing psychological treatment. To illustrate the proposed concept, a clinical scenario is also presented and discussed: Daniela, a 40 years old teacher, with a mother affected by Alzheimer's disease.

  1. An Instrumental Paradigm for Ubiquitous Interaction

    DEFF Research Database (Denmark)

    Klokmose, Clemens Nylandsted

    2008-01-01

    will require comprehensive experimental user centred development. Originality/Value -- This research offers a new way of thinking interaction, suited for the dynamism of modern computing. Take away message -- Through a strong foundation in activity theory and ecological psychology a new paradigm for ubiquitous...... shortcomings of some of the restrictive assumptions contemporary graphical user interfaces are built upon. Research approach -- Based on activity theory and ecological psychology a conceptual model for ubiquitous interaction is proposed and iteratively challenged and developed through actual implementation....... Findings/Design -- The project will ultimately shed light on how an understanding of interaction form activity theory and ecological psychology maps to an implementation of a new conceptual model for interaction with technology. Research limitations/Implications -- Implementation of an actual system...

  2. Social Media Guidelines and the News Paradigm

    DEFF Research Database (Denmark)

    Blumell, Lindsey; Hellmueller, Lea; Etter, Michael

    Social network use continues to increase in the majority of regions around the world, with a global increase of 17.6% in 2012, and another projected 12.6% in 2014 (digital.org, 2014). Social media have also been incorporated into daily routines of American journalists, with 53.8% reporting...... that they use microblogs like Twitter on a regular basis to both gather and disseminate information (Willnat & Weaver, 2014). The aim of this study is to investigate how social media, more specifically, social media guidelines, implemented at the organizational level intercede with journalism practices...... and if these guidelines challenge the news paradigm. While using social media have been a “loop-hole” of sorts to disseminating political information in countries that have strong censorship (the Arab Spring being a premiere example, Eltantawy & Wiest, 2011; Lotan, Graeff, Ananny, Gaffney, & Pearce, 2011), journalists...

  3. Implementing the Bayesian paradigm in risk analysis

    International Nuclear Information System (INIS)

    Aven, T.; Kvaloey, J.T.

    2002-01-01

    The Bayesian paradigm comprises a unified and consistent framework for analyzing and expressing risk. Yet, we see rather few examples of applications where the full Bayesian setting has been adopted with specifications of priors of unknown parameters. In this paper, we discuss some of the practical challenges of implementing Bayesian thinking and methods in risk analysis, emphasizing the introduction of probability models and parameters and associated uncertainty assessments. We conclude that there is a need for a pragmatic view in order to 'successfully' apply the Bayesian approach, such that we can do the assignments of some of the probabilities without adopting the somewhat sophisticated procedure of specifying prior distributions of parameters. A simple risk analysis example is presented to illustrate ideas

  4. The complexity paradigm in management reconceptualizing

    Directory of Open Access Journals (Sweden)

    Petrović Slavica P.

    2005-01-01

    Full Text Available Chaos and complexity theory is a special, functionalist systems approach to dealing with complex, dynamic, nonlinear systems. Through treating organizations as complex, with their environments coevolving, nonlinear systems, complexity theory is aimed at creative research of their erratic nature. When an organization is in a state of bounded instability, at the edge of chaos, order and disorder are intertwined, its behavior is irregular and unpredictable but has some pattern. According to the complexity paradigm organizations have to strive to avoid the equilibrium states of stability and instability. They have instead to strive to remain in a state of bounded instability, at the edge of chaos, where they are able to display their full potential for creativity and innovation.

  5. SLAVIC LITERATURES IN DALMATIAN PERIODICALS IN THE PERIOD OF CROATIAN MODERNISM

    Directory of Open Access Journals (Sweden)

    Robert Bacalja

    2010-01-01

    Full Text Available The paper analyzes translations and mediatorial articles from the Slavic literature published in Dalmatian newspapers and periodicals which contribute most to mediation during the period of Croatian Modernism. While periodicals in Dalmatia traditionally mediates from the Roman literature, especially from the Italian, in the examined corpus can be seen the remarkable reception of Slavic literature, particularly Russian.. The paradigm of the most recognized culture and literature in non Slavic world is desirable identity basis of the Croatian literature as a part of a large Slavic stem from romanticism to modernism. Mediation of Slavic literatures is examined on the corpus of newspapers and periodicals published in Dubrovnik, Split and Zadar (Crvena Hrvatska, Srđ, Sloboda, Jedinstvo/Novo jedinstvo, Novi vijek, Narodni list, Smotra dalmatinska, Iskra, Glasnik Matice dalmatinske, Lovor, etc..

  6. The search for understanding: the role of paradigms.

    Science.gov (United States)

    Kelly, Marcella; Dowling, Maura; Millar, Michelle

    2018-03-16

    Kuhn's ( 1962 ) acknowledgement of a paradigm as a way that scientists make sense of their world and its reality gave recognition to the idea of 'paradigm shift'. This shift exposes the transience of paradigm development shaped by societal and scientific evolution. This ongoing evolutionary development provides the researcher with many paradigms to consider regarding how research is undertaken and the search for understanding achieved. An understanding of paradigm development is necessary when planning a study and can shape the search for understanding. It is hoped that the discussion presented here will assist novice and experienced researchers in articulating the rationales for their paradigm choices. An overview of the dominant paradigms is presented, reflecting ongoing paradigm development shaped by ontological, epistemological and methodological perspectives. Potential paradigm choices that shape research aims, objectives and focus in the search for understanding are considered. The inherent debates about paradigm shift, division, war and synthesis leave the researcher many perspectives to consider. Articulating the world views underpinning constructivism, interpretivism and pragmatism is particularly challenging because of the blurring of boundaries between them. The evolutionary nature of paradigmatic development has provided nurse researchers with the opportunity for methodological openness to the myriad research approaches, methods and designs that they may choose to answer their research question. However, it is imperative that researchers consider their ontological stances and the nature of their research questions. This is challenging in constructivism, interpretivism and pragmatism, where there is often an overlap of paradigm world views. ©2018 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

  7. The Periodic Pyramid

    Science.gov (United States)

    Hennigan, Jennifer N.; Grubbs, W. Tandy

    2013-01-01

    The chemical elements present in the modern periodic table are arranged in terms of atomic numbers and chemical periodicity. Periodicity arises from quantum mechanical limitations on how many electrons can occupy various shells and subshells of an atom. The shell model of the atom predicts that a maximum of 2, 8, 18, and 32 electrons can occupy…

  8. Book Reviews in Periodicals.

    Science.gov (United States)

    Ettelt, Harold J.

    All recent issues of periodicals found which contain indexed book reviews are listed in this compilation from Drake Memorial Library at the New York State University at Brockport. The periodicals are listed by 29 subject headings in this informal guide designed to be used at Drake Library. The number of reviews in the periodical in a recent year…

  9. A Fluorescent Oligothiophene-Bis-Triazine ligand interacts with PrP fibrils and detects SDS-resistant oligomers in human prion diseases.

    Science.gov (United States)

    Imberdis, Thibaut; Ayrolles-Torro, Adeline; Duarte Rodrigues, Alysson; Torrent, Joan; Alvarez-Martinez, Maria Teresa; Kovacs, Gabor G; Verdier, Jean-Michel; Robitzer, Mike; Perrier, Véronique

    2016-01-26

    Prion diseases are characterized by the accumulation in the central nervous system of an abnormally folded isoform of the prion protein, named PrP(Sc). Aggregation of PrP(Sc) into oligomers and fibrils is critically involved in the pathogenesis of prion diseases. Oligomers are supposed to be the key neurotoxic agents in prion disease, so modulation of prion aggregation pathways with small molecules can be a valuable strategy for studying prion pathogenicity and for developing new diagnostic and therapeutic approaches. We previously identified thienyl pyrimidine compounds that induce SDS-resistant PrP(Sc) (rSDS-PrP(Sc)) oligomers in prion-infected samples. Due to the low effective doses of the thienyl pyrimidine hits, we synthesized a quaterthiophene-bis-triazine compound, called MR100 to better evaluate their diagnostic and therapeutic potentials. This molecule exhibits a powerful activity inducing rSDS-PrP(Sc) oligomers at nanomolar concentrations in prion-infected cells. Fluorescence interaction studies of MR100 with mouse PrP fibrils showed substantial modification of the spectrum, and the interaction was confirmed in vitro by production of rSDS-oligomer species upon incubation of MR100 with fibrils in SDS-PAGE gel. We further explored whether MR100 compound has a potential to be used in the diagnosis of prion diseases. Our results showed that: (i) MR100 can detect rSDS-oligomers in prion-infected brain homogenates of various species, including human samples from CJD patients; (ii) A protocol, called "Rapid Centrifugation Assay" (RCA), was developed based on MR100 property of inducing rSDS-PrP(Sc) oligomers only in prion-infected samples, and avoiding the protease digestion step. RCA allows the detection of both PK-sensitive and PK-resistant PrP(Sc) species in rodents samples but also from patients with different CJD forms (sporadic and new variant); (iii) A correlation could be established between the amount of rSDS-PrP(Sc) oligomers revealed by MR100 and the

  10. Affective Computing used in an imaging interaction paradigm

    DEFF Research Database (Denmark)

    Schultz, Nette

    2003-01-01

    This paper combines affective computing with an imaging interaction paradigm. An imaging interaction paradigm means that human and computer communicates primarily by images. Images evoke emotions in humans, so the computer must be able to behave emotionally intelligent. An affective image selection...

  11. Paradigms: How Far Does Research in Distributed Leadership "Stretch"?

    Science.gov (United States)

    Hartley, David

    2010-01-01

    Burrell and Morgan's widely-cited "Sociological Paradigms and Organizational Analysis" is applied here to research on distributed leadership in education. Nearly all of the extant research is regulatory, not radical; and the evidence which it has generated falls broadly within the paradigm of interpretivism. Few studies have generated the…

  12. Industry 4.0 and the New Simulation Modelling Paradigm

    Directory of Open Access Journals (Sweden)

    Rodič Blaž

    2017-08-01

    Full Text Available Background and Purpose: The aim of this paper is to present the influence of Industry 4.0 on the development of the new simulation modelling paradigm, embodied by the Digital Twin concept, and examine the adoption of the new paradigm via a multiple case study involving real-life R&D cases involving academia and industry.

  13. Disability Is Not Measles: New Research Paradigms in Disability.

    Science.gov (United States)

    Rioux, Marcia H., Ed.; Bach, Michael, Ed.

    This book is the product of a forum titled New Research Directions and Paradigms, held at the Congress of the International Association for the Scientific Study of Mental Deficiency in Australia in August 1992. The book presents 13 chapters, all written within a critical paradigm for disability research which critiques the reification of…

  14. Paradigms in the Gerontology Classroom: Connections and Challenges to Learning

    Science.gov (United States)

    Morgan, Leslie

    2012-01-01

    The article explores paradigms for approaching course content to be studied in the classroom. These paradigms, or global views about what is of interest or importance and ways of knowing, relate to key questions in gerontology, such as what is the relevant domain/content to be studied, what is the central level of analysis or action, what are…

  15. Interaction between Social Categories in the Composite Face Paradigm

    Science.gov (United States)

    Chen, Wenfeng; Ren, Naixin; Young, Andrew W.; Liu, Chang Hong

    2018-01-01

    The composite face paradigm (Young, Hellawell, & Hay, 1987) is widely used to demonstrate holistic perception of faces (Rossion, 2013). In the paradigm, parts from different faces (usually the top and bottom halves) are recombined. The principal criterion for holistic perception is that responses involving the component parts of composites in…

  16. [Nursing knowledge: the evolution of scientific philosophies and paradigm trends].

    Science.gov (United States)

    Hung, Hsuan-Man; Wang, Hui-Ling; Chang, Yun-Hsuan; Chen, Chung-Hey

    2010-02-01

    Different aspects of philosophy are derived from different paradigms that contain various main points, some of which are repeated or overlap. Belief and practice are two components of a paradigm that provide perspective and framework and lead to nursing research. Changes in healthcare have popularized empirical and evidence-based research in the field of nursing research. However, the evidence-base study approach has given rise to a certain level of debate. Until now, no standard paradigm has been established for the nursing field, as different professionals use different paradigms in their studies. Such provides certain limitations as well as advantages. The quantitative aspects of a nursing paradigm were developed by Peplau and Henderson (1950) and Orem (1980). Such remained the standard until 1990, when Guba and Parse proposed qualitative viewpoints in contextual features. Therefore, the nursing paradigm has made great contributions to the development of knowledge in nursing care, although debate continues due to incomplete knowledge attributable to the presentation of knowledge and insight within individually developed paradigms. It is better to apply multiple paradigms to different research questions. It is suggested that better communication amongst experts regarding their individual points of view would help nursing members to integrate findings within the global pool of knowledge and allow replication over multiple studies.

  17. Critical evaluation of paradigms for modelling integrated supply chains

    NARCIS (Netherlands)

    Van Dam, K.H.; Adhitya, A.; Srinivasan, R.; Lukszo, Z.

    2009-01-01

    Contemporary problems in process systems engineering often require model-based decision support tool. Among the various modelling paradigms, equation-based models and agent-based models are widely used to develop dynamic models of systems. Which is the most appropriate modelling paradigm for a

  18. A new learning paradigm: learning using privileged information.

    Science.gov (United States)

    Vapnik, Vladimir; Vashist, Akshay

    2009-01-01

    In the Afterword to the second edition of the book "Estimation of Dependences Based on Empirical Data" by V. Vapnik, an advanced learning paradigm called Learning Using Hidden Information (LUHI) was introduced. This Afterword also suggested an extension of the SVM method (the so called SVM(gamma)+ method) to implement algorithms which address the LUHI paradigm (Vapnik, 1982-2006, Sections 2.4.2 and 2.5.3 of the Afterword). See also (Vapnik, Vashist, & Pavlovitch, 2008, 2009) for further development of the algorithms. In contrast to the existing machine learning paradigm where a teacher does not play an important role, the advanced learning paradigm considers some elements of human teaching. In the new paradigm along with examples, a teacher can provide students with hidden information that exists in explanations, comments, comparisons, and so on. This paper discusses details of the new paradigm and corresponding algorithms, introduces some new algorithms, considers several specific forms of privileged information, demonstrates superiority of the new learning paradigm over the classical learning paradigm when solving practical problems, and discusses general questions related to the new ideas.

  19. Formal Epistemology and New Paradigm Psychology of Reasoning

    NARCIS (Netherlands)

    Pfeifer, Niki; Douven, Igor

    This position paper advocates combining formal epistemology and the new paradigm psychology of reasoning in the studies of conditionals and reasoning with uncertainty. The new paradigm psychology of reasoning is characterized by the use of probability theory as a rationality framework instead of

  20. A Comparison of Two Paradigms for Distributed Shared Memory

    NARCIS (Netherlands)

    Levelt, W.G.; Kaashoek, M.F.; Bal, H.E.; Tanenbaum, A.S.

    1992-01-01

    Two paradigms for distributed shared memory on loosely‐coupled computing systems are compared: the shared data‐object model as used in Orca, a programming language specially designed for loosely‐coupled computing systems, and the shared virtual memory model. For both paradigms two systems are

  1. Exponential time paradigms through the polynomial time lens

    NARCIS (Netherlands)

    Drucker, A.; Nederlof, J.; Santhanam, R.; Sankowski, P.; Zaroliagis, C.

    2016-01-01

    We propose a general approach to modelling algorithmic paradigms for the exact solution of NP-hard problems. Our approach is based on polynomial time reductions to succinct versions of problems solvable in polynomial time. We use this viewpoint to explore and compare the power of paradigms such as

  2. Researching Style: Epistemology, Paradigm Shifts and Research Interest Groups

    Science.gov (United States)

    Rayner, Stephen

    2011-01-01

    This paper identifies the need for a deliberate approach to theory building in the context of researching cognitive and learning style differences in human performance. A case for paradigm shift and a focus upon research epistemology is presented, building upon a recent critique of style research. A proposal for creating paradigm shift is made,…

  3. A Practical Examination of Two Diverse Research Paradigms

    Science.gov (United States)

    Brewer, Robert A.

    2007-01-01

    This manuscript examines the practical differences between quantitative and qualitative inquiry by comparing the differences between one article from each paradigm. Quantitative research differs greatly from qualitative inquiry in purpose, assumptions, methodology, and representation. While quantitative research has been the dominant paradigm for…

  4. Underlying Paradigms in Student Affairs Research and Practice

    Science.gov (United States)

    Guido, Florence M.; Chavez, Alicia Fedelina; Lincoln, Yvonna S.

    2010-01-01

    Student affairs professionals benefit from understanding paradigms, worldviews, and ways of being among diverse faculty, staff, and students. It is challenging to understand core differences of paradigms, design student affairs practice and research in congruence with or across specific philosophies, and work effectively with individuals operating…

  5. A Critical Evaluation of the Paradigm Approach in Sepedi ...

    African Journals Online (AJOL)

    user

    Abstract: This article gives a critical evaluation of the paradigm approach of the Groot Noord-. Sotho Woordeboek to the lemmatisation of verbs and nouns derived from verbs. The verb stem -roba. 'break' with its complicated system of derivations will be taken as a case in point. The paradigm presented for -roba will be ...

  6. The World Religions Paradigm Time for a Change

    Science.gov (United States)

    Owen, Suzanne

    2011-01-01

    The teaching of religions has long relied on the World Religions paradigm to guide curricula throughout education, which has led to a widening gap, on the one hand, between what is taught in schools and in universities and, on the other, between research and teaching. While the World Religions paradigm has allowed the inclusion of non-Christian…

  7. The Question of Work: Adolescent Literature and the Eriksonian Paradigm.

    Science.gov (United States)

    Burgan, Mary

    1988-01-01

    Suggests that focusing on paradigms of work--the way it is described, together with the thematic implications it embodies--can be useful in teaching literature to young adults. Examines how examples from literature illustrate Erik H. Erikson's paradigm of the psychosocial stages of development in late childhood and adolescence. (MM)

  8. A Paradigm for Learning in a World of Continuous Change

    Science.gov (United States)

    Thompson, Scott

    2014-01-01

    Through ongoing rapid-fire changes in the nature of communications, the social, professional, and political landscapes of our time are rapidly transforming. But the prevailing paradigm in most schools and school systems is a relic of the industrial revolution. Schools and school systems must adopt a new paradigm for learning if they are to remain…

  9. Sexual Violence through a Social Justice Paradigm: Framing and Applications

    Science.gov (United States)

    Hong, Luoluo; Marine, Susan B.

    2018-01-01

    In this chapter, we explore the factors that support the occurrence of sexual violence, including the role of interlocking systems of oppression. Traditional conceptions of "prevention" are deconstructed, a social justice paradigm for addressing sexual violence is advanced, and examples of how the paradigm can be applied to practice are…

  10. The Membrane Paradigm and black-hole thermodynamics

    International Nuclear Information System (INIS)

    Thorne, K.S.

    1986-01-01

    A brief overview is given of the theoretical underpinnings of the Membrane Paradigm for black-hole physics. Then those underpinnings are used to elucidate the Paradigm's view that the laws of black-hole thermodynamics (including the statistical origin of black-hole entropy) are just a special case of the laws of thermodynamics for an ordinary, rotating, thermal reservoir

  11. Towards a Paradigm Shift in Educational Research: A Case of ...

    African Journals Online (AJOL)

    The postcolonial theory paradigm guided the study. The article reviews literature on the postcolonial theory with the objective of illustrating how this research paradigm may be employed in the field of education in a postcolonial context. The origin, purpose and relevance of the postcolonial theory are brought to the fore as ...

  12. Motor imagery enhancement paradigm using moving rubber hand illusion system.

    Science.gov (United States)

    Minsu Song; Jonghyun Kim

    2017-07-01

    Motor imagery (MI) has been widely used in neurorehabilitation and brain computer interface. The size of event-related desynchronization (ERD) is a key parameter for successful motor imaginary rehabilitation and BCI adaptation. Many studies have used visual guidance for enhancement/ amplification of motor imagery ERD amplitude, but their enhancements were not significant. We propose a novel ERD enhancing paradigm using body-ownership illusion, or also known as rubber hand illusion (RHI). The system was made by motorized, moving rubber hand which can simulate wrist extension. The amplifying effects of the proposed RHI paradigm were evaluated by comparing ERD sizes of the proposed paradigm with motor imagery and actual motor execution paradigms. The comparison result shows that the improvement of ERD size due to the proposed paradigm was statistically significant (pparadigms.

  13. A Cultural Paradigm--Learning by Observing and Pitching In.

    Science.gov (United States)

    Rogoff, Barbara; Mejía-Arauz, Rebeca; Correa-Chávez, Maricela

    2015-01-01

    We discuss Learning by Observing and Pitching In (LOPI) as a cultural paradigm that provides an interesting alternative to Assembly-Line Instruction for supporting children's learning. Although LOPI may occur in all communities, it appears to be especially prevalent in many Indigenous and Indigenous-heritage communities of the Americas. We explain key features of this paradigm, previewing the chapters of this volume, which examine LOPI as it occurs in the lives of families and communities. In this introductory chapter, we focus especially on one feature of the paradigm that plays an important role in its uptake and maintenance in families, institutions, and communities-the nature of assessment. We consider the power of the dominant paradigm and the challenges in making paradigm shifts. © 2015 Elsevier Inc. All rights reserved.

  14. Revisiting System Paradigms from the Viewpoint of Manufacturing Sustainability

    Directory of Open Access Journals (Sweden)

    Zhuming Bi

    2011-08-01

    Full Text Available A system paradigm is an abstract representation of system; it includes system architecture used to determine the types and numbers of components and their relations in the system. The design of system paradigm relies on customers’ requirements and the characteristics of the manufacturing environment. Many system paradigms and design guidelines have been proposed for a variety of customers’ needs including functions, cost, quality, personalization, and lead time of products. However, the consideration of sustainability becomes essential to today’s manufacturing systems; a new challenge is how to evolve existing paradigms to accommodate the requirements of sustainability. In contrast to ample research activities on system paradigms in past decades, recent studies on system paradigms have been restricted, partially due to unclear research directions. Limited works can be found on conceiving new manufacturing system paradigms from the perspective of sustainability; most of the related literature concerns the new requirements of sustainability. The objectives of this work are (i to examine the requirements of manufacturing systems in a wider scope; (ii to revisit existing paradigms to clarify their limitations and bottlenecks; and eventually (iii to identify some research directions, which will lead to a solution of sustainable manufacturing. To achieve these objectives, firstly, a brief description of today’s manufacturing environment is provided. Secondly, the requirements of sustainability are discussed, and the relevant researches on system sustainability are surveyed. Thirdly, the reconfigurable system paradigm is focused, and the gaps between a reconfigurable manufacturing system and a sustainable manufacturing system are discussed. Finally, the future endeavors towards to the next-generation manufacturing system paradigms are discussed.

  15. Paradigms and nursing management, analysis of the current organizational structure in a large hospital.

    Science.gov (United States)

    Wilson, D

    1992-01-01

    Hospitals developed over the period of time when positivism become a predominant world view. Positivism was founded by four Western trends: preponderance of hierarchy and autocracy, popularization of bureaucracy, extensive application of a machine orientation to work and predominance of "scientific" inquiry. Organizational theory developed largely from quantitative research findings arising from a positivistic world view. A case study, analyzing a current nursing organizational structure at one large hospital, is presented. Nursing management was found to be based upon the positivistic paradigm. The predominance of a machine orientation, and an autocratic and bureaucratic structure are evidence of this. A change to shared governance had been attempted, indicating a shift to a more modern organizational structure based on a different paradigm. The article concludes by emphasizing that managers are largely responsible for facilitating change; change that will meet internal human resource needs and the cost-effectiveness crises of hospitals today through more effective use of human resources.

  16. The Digital Twin Paradigm for Future NASA and U.S. Air Force Vehicles

    Science.gov (United States)

    Glaessgen, Edward H.; Stargel, D. S.

    2012-01-01

    Future generations of NASA and U.S. Air Force vehicles will require lighter mass while being subjected to higher loads and more extreme service conditions over longer time periods than the present generation. Current approaches for certification, fleet management and sustainment are largely based on statistical distributions of material properties, heuristic design philosophies, physical testing and assumed similitude between testing and operational conditions and will likely be unable to address these extreme requirements. To address the shortcomings of conventional approaches, a fundamental paradigm shift is needed. This paradigm shift, the Digital Twin, integrates ultra-high fidelity simulation with the vehicle s on-board integrated vehicle health management system, maintenance history and all available historical and fleet data to mirror the life of its flying twin and enable unprecedented levels of safety and reliability.

  17. A modified parallel paradigm for clinical evaluation of auditory echoic memory.

    Science.gov (United States)

    Karino, Shotaro; Yumoto, Masato; Itoh, Kenji; Yamakawa, Keiko; Mizuochi, Tomomi; Kaga, Kimitaka

    2005-05-12

    We established a new parallel paradigm for mismatch negativity by presenting repetitive trains of three consonant-vowel syllables and those of three sinusoidal tones alternately. Magnetoencephalography was performed to test the new method, and mismatch negativities in six study participants with normal hearing were compared with the results of the conventional oddball paradigm. Peak amplitude and latencies of mismatch negativity showed no significant difference between the methods. The maximum amplitude in short memory probe interval of 1.0 s was significantly larger than in long memory probe interval of 3.0 s, demonstrating decay in auditory echoic memory caused by a prolonged memory probe interval. The new method facilitated simultaneous evaluation of mismatch negativity with various stimuli in a shorter period.

  18. Anthropology of music: Paradigms and perspectives

    Directory of Open Access Journals (Sweden)

    Rašić Miloš

    2016-01-01

    Full Text Available Music represents a relational category, in the sense that people write meaning into it, and later by the means of the same music they write the meaning into other people. Therefore, I regard music as a cultural construct. Music does not possess universal meanings, but it forms its numerous meanings in different cultural environments, as well as in different individual perceptions. In anthropology, music is not studied in relation to its musical characteristics or aesthetical values. Anthropologists study its role in a wider social system, and strive to understand, by analysing the role of music in a society, the social and cultural system it belongs to - musical structure is less important here. The goal of the paper is to give an overview of the paradigms in ethnology and anthropology which have been used in studying music. In addition, a hypothetical-theoretical framework for studying music in institutions is set. Although the theory of hubs, which is presented here as a potential framework for studying music in institutions, is exemplified by traditional music, it can be applied to any genre of music. The basic theoretical framework offered by the authors Nadia Kiwan and Hanna Mainhof has been supplemented by certain parts which the author thought appropriate for studying music in institutions, both in ethnological and anthropological discourse.

  19. Paradigm transition in cosmic plasma physics

    International Nuclear Information System (INIS)

    Alfven, H.

    1982-01-01

    In situ measurements in the magnetospheres together with general advancement in plasma physics are now necessitating introduction of a number of effects that have been recently discovered or earlier neglected. Examples are: electric double layers (like in the lower magnetosphere); thin current layer (like in the magnetopause) giving space a cellular structure; current produced filaments (e.g., in prominences, solar corona and interstellar clouds). Further it is important to use the electric current (particle) description and to study the whole circuit in which the current flows. The pinch effect cannot be neglected as is now usually done. The critical velocity phenomenon is essential, for example for the band structure of solar system. Theory of dusty plasmas is important. The result is a change in so many theories in cosmic plasma physics that it is appropriate to speak of an introduction of a new paradigm. This should be based on empirical knowledge from magnetospheric and laboratory investigations. Its application to astrophysics in general, including cosmology, will necessarily lead to a revision of, e.g., the present theories of the formation of stars, planets and satellites. It is doubtful whether the big bang cosmology will survive. (Auth.)

  20. Changing the paradigm for engineering ethics.

    Science.gov (United States)

    Schmidt, Jon Alan

    2014-12-01

    Modern philosophy recognizes two major ethical theories: deontology, which encourages adherence to rules and fulfillment of duties or obligations; and consequentialism, which evaluates morally significant actions strictly on the basis of their actual or anticipated outcomes. Both involve the systematic application of universal abstract principles, reflecting the culturally dominant paradigm of technical rationality. Professional societies promulgate codes of ethics with which engineers are expected to comply (deontology), while courts and the public generally assign liability to engineers primarily in accordance with the results of their work, whether intended or unintended (consequentialism). A third option, prominent in ancient philosophy, has reemerged recently: virtue ethics, which recognizes that sensitivity to context and practical judgment are indispensable in particular concrete situations, and therefore rightly focuses on the person who acts, rather than the action itself. Beneficial character traits--i.e., virtues--are identified within a specific social practice in light of the internal goods that are unique to it. This paper proposes a comprehensive framework for implementing virtue ethics within engineering.

  1. The future of management: The NASA paradigm

    Science.gov (United States)

    Harris, Philip R.

    1992-01-01

    Prototypes of 21st century management, especially for large scale enterprises, may well be found within the aerospace industry. The space era inaugurated a number of projects of such scope and magnitude that another type of management had to be created to ensure successful achievement. The challenges will be not just in terms of technology and its management, but also human and cultural in dimension. Futurists, students of management, and those concerned with technological administration would do well to review the literature of emerging space management for its wider implications. NASA offers a paradigm, or demonstrated model, of future trends in the field of management at large. More research is needed on issues of leadership for Earth based project in space and space based programs with managers there. It is needed to realize that large scale technical enterprises, such as are undertaken in space, require a new form of management. NASA and other responsible agencies are urged to study excellence in space macromanagement, including the necessary multidisciplinary skills. Two recommended targets are the application of general living systems theory and macromanagement concepts for space stations in the 1990s.

  2. International trade disputes in modern regulatory paradigm

    Directory of Open Access Journals (Sweden)

    Tamara Gordeeva

    2013-09-01

    Full Text Available This article studies the latest trends observed in the area of contradictory relations between countries with regard to international trade, which cause changes in the paradigm of international trade disputes. It has been found out that any state of inconsistent relations between the countries is recently characterized as a «trade war». It has been analyzed the notions of «dispute», «conflict», «war» according to international regulatory documents and determined the applicability of these terms depending on a number of criteria. It has been studied the evolution of the objects of international trade disputes since the time of ancient Greece until today, and new trends based on this have been revealed with regard to use of trade policy instruments that cause disputes between countries. Several specific examples of international trade disputes and causes of their occurrence have been considered. A quantitative analysis of international trade disputes in general and in relations between the leading countries in terms of a number of the trade disputes in which they were involved has been performed.

  3. Inflationary paradigm in trouble after Planck2013

    Energy Technology Data Exchange (ETDEWEB)

    Ijjas, Anna, E-mail: aijjas@cfa.harvard.edu [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); University Observatory Munich, 81679 Munich (Germany); Steinhardt, Paul J., E-mail: steinh@princeton.edu [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Department of Physics, Princeton University, Princeton, NJ 08544 (United States); Princeton Center for Theoretical Science, Princeton University, Princeton, NJ 08544 (United States); Loeb, Abraham, E-mail: aloeb@cfa.harvard.edu [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States)

    2013-06-25

    Recent results from the Planck satellite combined with earlier observations from WMAP, ACT, SPT and other experiments eliminate a wide spectrum of more complex inflationary models and favor models with a single scalar field, as reported by the Planck Collaboration. More important, though, is that all the simplest inflaton models are disfavored statistically relative to those with plateau-like potentials. We discuss how a restriction to plateau-like models has three independent serious drawbacks: it exacerbates both the initial conditions problem and the multiverse-unpredictability problem and it creates a new difficulty that we call the inflationary “unlikeliness problem.” Finally, we comment on problems reconciling inflation with a standard model Higgs, as suggested by recent LHC results. In sum, we find that recent experimental data disfavors all the best-motivated inflationary scenarios and introduces new, serious difficulties that cut to the core of the inflationary paradigm. Forthcoming searches for B-modes, non-Gaussianity and new particles should be decisive.

  4. Bitters: Time for a New Paradigm

    Directory of Open Access Journals (Sweden)

    Michael K. McMullen

    2015-01-01

    Full Text Available In plant-based medical systems, bitter tasting plants play a key role in managing dyspepsia. Yet when it comes to defining their mechanism of activity, herbalists and pharmacologists are split between two theories: one involves cephalic elicited vagal responses while the other comprises purely local responses. Recent studies indicate that bitters elicit a range of cephalic responses which alter postprandial gastric phase haemodynamics. Caffeine and regular coffee (Coffea arabica semen, L. increase heart rate whereas gentian (Gentiana lutea radix, L. and wormwood (Artemisia absinthium herba L. increase tonus in the vascular resistance vessels. Following meals increased cardiac activity acts to support postprandial hyperaemia and maintain systemic blood pressure. The increased vascular tonus acts in parallel with the increased cardiac activity and in normal adults this additional pressor effect results in a reduced cardiac workload. The vascular response is a sympathetic reflex, evident after 5 minutes and dose dependent. Thus gentian and wormwood elicit cephalic responses which facilitate rather than stimulate digestive activity when postprandial hyperaemia is inadequate. Encapsulated caffeine elicits cardiovascular responses indicating that gastrointestinal bitter receptors are functionally active in humans. However, neither encapsulated gentian nor wormwood elicited cardiovascular responses during the gastric phase. These findings provide the platform for a new evidence-based paradigm.

  5. Bitters: Time for a New Paradigm.

    Science.gov (United States)

    McMullen, Michael K; Whitehouse, Julie M; Towell, Anthony

    2015-01-01

    In plant-based medical systems, bitter tasting plants play a key role in managing dyspepsia. Yet when it comes to defining their mechanism of activity, herbalists and pharmacologists are split between two theories: one involves cephalic elicited vagal responses while the other comprises purely local responses. Recent studies indicate that bitters elicit a range of cephalic responses which alter postprandial gastric phase haemodynamics. Caffeine and regular coffee (Coffea arabica semen, L.) increase heart rate whereas gentian (Gentiana lutea radix, L.) and wormwood (Artemisia absinthium herba L.) increase tonus in the vascular resistance vessels. Following meals increased cardiac activity acts to support postprandial hyperaemia and maintain systemic blood pressure. The increased vascular tonus acts in parallel with the increased cardiac activity and in normal adults this additional pressor effect results in a reduced cardiac workload. The vascular response is a sympathetic reflex, evident after 5 minutes and dose dependent. Thus gentian and wormwood elicit cephalic responses which facilitate rather than stimulate digestive activity when postprandial hyperaemia is inadequate. Encapsulated caffeine elicits cardiovascular responses indicating that gastrointestinal bitter receptors are functionally active in humans. However, neither encapsulated gentian nor wormwood elicited cardiovascular responses during the gastric phase. These findings provide the platform for a new evidence-based paradigm.

  6. Diverticular Disease: Traditional and Evolving Paradigms.

    Science.gov (United States)

    Lamanna, Lenore; Moran, Patricia E

    Diverticular disease includes diverticulosis, which are sac protrusions of the intestinal mucosa, and diverticulitis, inflammation of the diverticula. Diverticular disease is listed as one of the top 10 leading physician diagnoses for gastrointestinal disorders in outpatient clinic visits in the United States. There are several classifications of diverticular disease ranging from asymptomatic diverticulosis to diverticulitis with complications. Several theories are linked to the development of diverticula which includes the physiology of the colon itself, collagen cross-linking, and recently challenged, low-fiber intake. The differential diagnoses of lower abdominal pain in addition to diverticular disease have overlapping signs and symptoms, which can make a diagnosis challenging. Identification of the distinct signs and symptoms of each classification will assist the practitioner in making the correct diagnosis and lead to appropriate management. The findings from recent studies have changed the paradigm of diverticular disease. The purpose of this article is to discuss traditional dogma and evolving concepts in the pathophysiology, prevention, and management of diverticular disease. Practitioners must be knowledgeable about diverticular disease for improved outcomes.

  7. Biofabrication: a 21st century manufacturing paradigm

    International Nuclear Information System (INIS)

    Mironov, V; Trusk, T; Markwald, R; Kasyanov, V; Little, S; Swaja, R

    2009-01-01

    Biofabrication can be defined as the production of complex living and non-living biological products from raw materials such as living cells, molecules, extracellular matrices, and biomaterials. Cell and developmental biology, biomaterials science, and mechanical engineering are the main disciplines contributing to the emergence of biofabrication technology. The industrial potential of biofabrication technology is far beyond the traditional medically oriented tissue engineering and organ printing and, in the short term, it is essential for developing potentially highly predictive human cell- and tissue-based technologies for drug discovery, drug toxicity, environmental toxicology assays, and complex in vitro models of human development and diseases. In the long term, biofabrication can also contribute to the development of novel biotechnologies for sustainable energy production in the future biofuel industry and dramatically transform traditional animal-based agriculture by inventing 'animal-free' food, leather, and fur products. Thus, the broad spectrum of potential applications and rapidly growing arsenal of biofabrication methods strongly suggests that biofabrication can become a dominant technological platform and new paradigm for 21st century manufacturing. The main objectives of this review are defining biofabrication, outlining the most essential disciplines critical for emergence of this field, analysis of the evolving arsenal of biofabrication technologies and their potential practical applications, as well as a discussion of the common challenges being faced by biofabrication technologies, and the necessary conditions for the development of a global biofabrication research community and commercially successful biofabrication industry. (topical review)

  8. Biofabrication: a 21st century manufacturing paradigm.

    Science.gov (United States)

    Mironov, V; Trusk, T; Kasyanov, V; Little, S; Swaja, R; Markwald, R

    2009-06-01

    Biofabrication can be defined as the production of complex living and non-living biological products from raw materials such as living cells, molecules, extracellular matrices, and biomaterials. Cell and developmental biology, biomaterials science, and mechanical engineering are the main disciplines contributing to the emergence of biofabrication technology. The industrial potential of biofabrication technology is far beyond the traditional medically oriented tissue engineering and organ printing and, in the short term, it is essential for developing potentially highly predictive human cell- and tissue-based technologies for drug discovery, drug toxicity, environmental toxicology assays, and complex in vitro models of human development and diseases. In the long term, biofabrication can also contribute to the development of novel biotechnologies for sustainable energy production in the future biofuel industry and dramatically transform traditional animal-based agriculture by inventing 'animal-free' food, leather, and fur products. Thus, the broad spectrum of potential applications and rapidly growing arsenal of biofabrication methods strongly suggests that biofabrication can become a dominant technological platform and new paradigm for 21st century manufacturing. The main objectives of this review are defining biofabrication, outlining the most essential disciplines critical for emergence of this field, analysis of the evolving arsenal of biofabrication technologies and their potential practical applications, as well as a discussion of the common challenges being faced by biofabrication technologies, and the necessary conditions for the development of a global biofabrication research community and commercially successful biofabrication industry.

  9. Spirituality in Contemporary Paradigms: An Integrative Review

    Directory of Open Access Journals (Sweden)

    Monir Ramezani

    2016-07-01

    Full Text Available Background: As two of the most prominent cultural components, spirituality and religion give sense to our human values, conducts, and experiences. The spiritual dimension is one of the four significant aspects of holistic care. However, the diversity of views has resulted in different interpretations of the reality of spirituality and its origins and consequences. Aim: This study aimed to examine the available approaches and paradigms in the realm of spirituality. Method: In the present integrative review, the initial search was performed in national and international databases, including Science Direct, PubMed, Google Scholar, Scopus, Sage, Medline, Wiley, SID, MagIran, IranMedex, and IranDoc, using the keyword, "spirituality", without considering any time limits. Articles relevant to the objectives of the study were then fully reviewed. Results: Since ancient times, spirituality has been sporadically discussed in human intellectual and artistic artifacts. This concept was expanded as an independent, systematic, and conscious movement since the second half of the 19th century in Europe, USA, and Canada. The three prominent approaches to spirituality include religious, secular, and holistic health perspectives. Implications for Practice: Despite the growing interest in research on spirituality, it is difficult to reach a unanimous decision about this concept. However, it should be noted that spiritual concerns cannot be disregarded, considering the holistic perspective to humanity as the building block of holistic nursing care. Overall, every patient is a unique human being whose spiritual needs are affected by his/her cultural beliefs and values.

  10. Paradigm transition in cosmic plasma physics

    International Nuclear Information System (INIS)

    Alfven, H.

    1982-06-01

    In situ measurements in the magnetospheres together with general advancement in plasma physics are now necessitating introduction of a number of effects that have been recently discovered or earlier neglected. Examples are: 1) Electric double layers (like in the lower magnetosphere) 2) Thin current layer (like in the magnetopause) giving space a cellular structure. 3) Current produced filaments (e.g. in prominences, solar corona and interstellar clouds). 4) Further it is important to use the electric current (particle) description and to study the whole circuit in which the current flows. 5) The pinch effect cannot be neglected as is now usually done. 6) The critical velocity phenomenon is essential, for example for the band structure of solar systems. 7) Theory of dusty plasmas is important. The result is a change in so many theories in cosmic plasma physics that it is appropriate to speak of an introduction of a new paradigm. This should be based on empirical knowledge from magnetospheric and laboratory investigations. Its application to astrophysics in general, including cosmology, will necessarily lead to a revision of e.g. the present theories of the formation of stars, planets and satellites. It is doubtful whether the big bang cosmology will survive. (Author)

  11. A LEGO paradigm for virtual accelerator concept

    International Nuclear Information System (INIS)

    Andrianov, S.; Ivanov, A.; Podzyvalov, E.

    2012-01-01

    The paper considers basic features of a Virtual Accelerator concept based on LEGO paradigm. This concept involves three types of components: different mathematical models for accelerator design problems, integrated beam simulation packages (i. e. COSY, MAD, OptiM and others), and a special class of virtual feedback instruments similar to real control systems (EPICS). All of these components should inter-operate for more complete analysis of control systems and increased fault tolerance. The Virtual Accelerator is an information and computing environment which provides a framework for analysis based on these components that can be combined in different ways. Corresponding distributed computing services establish interaction between mathematical models and low level control system. The general idea of the software implementation is based on the Service-Oriented Architecture (SOA) that allows using cloud computing technology and enables remote access to the information and computing resources. The Virtual Accelerator allows a designer to combine powerful instruments for modeling beam dynamics in a friendly way including both self-developed and well-known packages. In the scope of this concept the following is also proposed: the control system identification, analysis and result verification, visualization as well as virtual feedback for beam line operation. The architecture of the Virtual Accelerator system itself and results of beam dynamics studies are presented. (authors)

  12. Integrated reporting – innovation in accounting paradigms

    Directory of Open Access Journals (Sweden)

    Mirosława Kwiecień

    2016-07-01

    Full Text Available The article is an introduction to the issues and results of a new trend in interdisciplinary research, which is integrated reporting. „Violated balance”, characteristic of contemporary global economy, forces us to seek solutions oriented to symbiosis between economic, social and environmental progress, which is the basis for fundamental changes in mental models that determine the way the economic organization oper-ates. On the basis of literature studies, as well as management (of innovation, knowledge, etc. science studies and research on changes in legal regulations of accounting, one can venture to say that the change in accounting paradigms is an innovation which stems from legal requirements. Legislation stimulates conceptuality, including information management, standardization of accounting, etc. Innovation theory refers to technological, organizational and market changes, so a question ariseswhether this theory can be applied to accounting practices as well? In this way an idea emerged for inves-tigating the question if the implementation of legal regulations such as International Financial Reporting Standards (IFRS or the standards of the Global Reporting Initiative (GRI is a manifestation of the inno-vation theory in the development of accounting systems, especially in reporting.

  13. Citizen utilities: The emerging power paradigm

    International Nuclear Information System (INIS)

    Green, Jemma; Newman, Peter

    2017-01-01

    The emergence of citizen-based power systems in an integrated grid has been anticipated for decades. We can reveal how this is emerging in practice due to the significant uptake of solar photovoltaics (solar PV) and now battery storage in Perth, Australia. The high cost of electricity, high radiant energy levels and easy access to cheap Chinese technology, has led to dramatic buying during Perth's recent boomtown years. The traditional uni-directional power system is rapidly disrupting and this paper assesses where this may lead and what it means for the grid. Results of detailed monitoring in a solar powered house along with the impact of a battery storage system show the impact on the traditional grid is substantial but it will still be needed and must therefore adapt to the new distributed, bi-directional energy system. Surveys and price trajectories reveal how the trends to solar power storage will continue and how a citizen utility paradigm will emerge as the future grid building block using new blockchain support systems. Responses from utilities are then see to be fight, flight or innovate. - Highlights: • Citizen based power systems are emerging in Perth, Western Australia. • Solar power and battery storage systems are disrupting traditional utilities. • The grid will still have a role in the new, distributed power system. • The new system will lead to economic localism and the democratisation of power.

  14. An automated paradigm for Drosophila visual psychophysics.

    Directory of Open Access Journals (Sweden)

    Oliver Evans

    Full Text Available BACKGROUND: Mutations that cause learning and memory defects in Drosophila melanogaster have been found to also compromise visual responsiveness and attention. A better understanding of attention-like defects in such Drosophila mutants therefore requires a more detailed characterization of visual responsiveness across a range of visual parameters. METHODOLOGY/PRINCIPAL FINDINGS: We designed an automated behavioral paradigm for efficiently dissecting visual responsiveness in Drosophila. Populations of flies walk through multiplexed serial choice mazes while being exposed to moving visuals displayed on computer monitors, and infra-red fly counters at the end of each maze automatically score the responsiveness of a strain. To test our new design, we performed a detailed comparison between wild-type flies and a learning and memory mutant, dunce(1. We first confirmed that the learning mutant dunce(1 displays increased responsiveness to a black/green moving grating compared to wild type in this new design. We then extended this result to explore responses to a wide range of psychophysical parameters for moving gratings (e.g., luminosity, contrast, spatial frequency, velocity as well as to a different stimulus, moving dots. Finally, we combined these visuals (gratings versus dots in competition to investigate how dunce(1 and wild-type flies respond to more complex and conflicting motion effects. CONCLUSIONS/SIGNIFICANCE: We found that dunce(1 responds more strongly than wild type to high contrast and highly structured motion. This effect was found for simple gratings, dots, and combinations of both stimuli presented in competition.

  15. Current treatment paradigms in rheumatoid arthritis.

    Science.gov (United States)

    Fries, J F

    2000-06-01

    Rheumatoid arthritis (RA) has traditionally been treated using the pyramid approach, in which non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment and disease-modifying anti-rheumatic drugs (DMARDs) are introduced relatively late in the disease. This approach is no longer valid. Previously regarded as a benign disease, RA is now recognized as causing substantial morbidity and mortality, as do the NSAIDs used in treatment. DMARDs are more effective in controlling the pain and disability of RA than NSAIDs, and are often no more toxic. The current treatment paradigm emphasizes early, consistent use of DMARDs. A 'sawtooth' strategy of DMARD use has been proposed, in which a rising but low level of disability triggers a change in therapy. Determining the most clinically useful DMARD combinations and the optimal sequence of DMARD use requires effectiveness studies, Bayesian approaches and analyses of long-term outcomes. Such approaches will allow optimization of multiple drug therapies in RA, and should substantially improve the long-term outcome for many patients.

  16. Paradigms and Paradoxes: Dawn at Vesta

    Science.gov (United States)

    Raymond, Carol; Russell, Christopher; Mittlefehldt, David

    2014-05-01

    While confirming the paradigm of Vesta as the parent body of the HED meteorites, measurements by Dawn have discovered many unexpected aspects of the vestan surface. First, an olivine layer was not found in the bottom of the large basin near the south pole of Vesta where excavation of the mantle was thought to have occurred. In fact, while patches of olivine have been found in the north, it is rare on the surface. Secondly, while Vesta has little gravity and appears to have completely differentiated, it is not completely dry. Morphological evidence from the walls and floors of some craters suggest transient fluid flows and pits formed by devolatization, implying a substantial amount of accessible water. The question is, did this water derive from internal or external sources? Thirdly, transport of material to the surface of Vesta from elsewhere in the asteroid belt appears as dark material buried near the top of the regolith of Vesta. This may have arrived in a single large impact and been spread around the surface and buried, later to be re-excavated. However, this is not the only scenario possible for the source of this material. Meteoritical evidence from howardites shows that debris from multiple types of impactors are present in the vestan regolith. In short, Dawn's observations of Vesta have been both reassuring but unsettling at the same time.

  17. Methodological pitfalls of the Unconscious Thought paradigm

    NARCIS (Netherlands)

    Waroquier, Laurent; Marchiori, David; Klein, Olivier; Cleeremans, Axel

    2009-01-01

    According to Unconscious Thought Theory (UTT: Dijksterhuis & Nordgren, 2006), complex decisions are best made after a period of distraction assumed to elicit "unconscious thought". Over three studies, respectively offering a conceptual, an identical and a methodologically improved replication of

  18. Painful menstrual periods

    Science.gov (United States)

    Menstruation - painful; Dysmenorrhea; Periods - painful; Cramps - menstrual; Menstrual cramps ... into two groups, depending on the cause: Primary dysmenorrhea Secondary dysmenorrhea Primary dysmenorrhea is menstrual pain that ...

  19. Middle Helladic Period

    DEFF Research Database (Denmark)

    Sarri, Kalliopi

    1999-01-01

    and their quality was improved considerably toward the end of this period. The profound cultural innovations of the Middle Helladic period were initially interpreted as a result of violent population movement and troubles provoked by the coming of the first Indo-European races. However, this matter does no more...... Helladic period is considered as a period of economic and social decline it was the time during which the mainland features merged with the insular influence, that is all the Aegean elements which led to the creation of the Mycenaean civilization were mixed in a creative way....

  20. [New paradigm for soil and water conservation: a method based on watershed process modeling and scenario analysis].

    Science.gov (United States)

    Zhu, A-Xing; Chen, La-Jiao; Qin, Cheng-Zhi; Wang, Ping; Liu, Jun-Zhi; Li, Run-Kui; Cai, Qiang-Guo

    2012-07-01

    With the increase of severe soil erosion problem, soil and water conservation has become an urgent concern for sustainable development. Small watershed experimental observation is the traditional paradigm for soil and water control. However, the establishment of experimental watershed usually takes long time, and has the limitations of poor repeatability and high cost. Moreover, the popularization of the results from the experimental watershed is limited for other areas due to the differences in watershed conditions. Therefore, it is not sufficient to completely rely on this old paradigm for soil and water loss control. Recently, scenario analysis based on watershed modeling has been introduced into watershed management, which can provide information about the effectiveness of different management practices based on the quantitative simulation of watershed processes. Because of its merits such as low cost, short period, and high repeatability, scenario analysis shows great potential in aiding the development of watershed management strategy. This paper elaborated a new paradigm using watershed modeling and scenario analysis for soil and water conservation, illustrated this new paradigm through two cases for practical watershed management, and explored the future development of this new soil and water conservation paradigm.

  1. On some periodicity effects

    DEFF Research Database (Denmark)

    Sorokin, Sergey V.

    2015-01-01

    The talk is concerned with the modelling of wave propagation in and vibration of periodic elastic structures. Although analysis of wave-guide properties of infinite periodic structures is a well establish research subject, some issues have not yet been fully addressed in the literature. The aim o...

  2. The Living Periodic Table

    Science.gov (United States)

    Nahlik, Mary Schrodt

    2005-01-01

    To help make the abstract world of chemistry more concrete eighth-grade students, the author has them create a living periodic table that can be displayed in the classroom or hallway. This display includes information about the elements arranged in the traditional periodic table format, but also includes visual real-world representations of the…

  3. A nomenclature paradigm for benign midmembranous vocal fold lesions.

    Science.gov (United States)

    Rosen, Clark A; Gartner-Schmidt, Jackie; Hathaway, Bridget; Simpson, C Blake; Postma, Gregory N; Courey, Mark; Sataloff, Robert T

    2012-06-01

    There is a significant lack of uniform agreement regarding nomenclature for benign vocal fold lesions (BVFLs). This confusion results in difficulty for clinicians communicating with their patients and with each other. In addition, BVFL research and comparison of treatment methods are hampered by the lack of a detailed and uniform BVFL nomenclature. Clinical consensus conferences were held to develop an initial BVFL nomenclature paradigm. Perceptual video analysis was performed to validate the stroboscopy component of the paradigm. The culmination of the consensus conferences and the video-perceptual analysis was used to evaluate the BVFL nomenclature paradigm using a retrospective review of patients with BVFL. An initial BVFL nomenclature paradigm was proposed utilizing detailed definitions relating to vocal fold lesion morphology, stroboscopy, response to voice therapy and intraoperative findings. Video-perceptual analysis of stroboscopy demonstrated that the proposed binary stroboscopy system used in the BVFL nomenclature paradigm was valid and widely applicable. Retrospective review of 45 patients with BVFL followed to the conclusion of treatment demonstrated that slight modifications of the initial BVFL nomenclature paradigm were required. With the modified BVFL nomenclature paradigm, 96% of the patients fit into the predicted pattern and definitions of the BVFL nomenclature system. This study has validated a multidimensional BVFL nomenclature paradigm. This vocal fold nomenclature paradigm includes nine distinct vocal fold lesions: vocal fold nodules, vocal fold polyp, pseudocyst, vocal fold cyst (subepithelial or ligament), nonspecific vocal fold lesion, vocal fold fibrous mass (subepithelial or ligament), and reactive lesion. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  4. Innovative technological paradigm-based approach towards biofuel feedstock

    International Nuclear Information System (INIS)

    Xu, Jiuping; Li, Meihui

    2017-01-01

    Highlights: • DAS was developed through an innovative approach towards literature mining and technological paradigm theory. • A novel concept of biofuel feedstock development paradigm (BFDP) is proposed. • The biofuel production diffusion velocity model gives predictions for the future. • Soft path appears to be the driving force for the new paradigm shift. • An integrated biofuel production feedstock system is expected to play a significant role in a low-carbon sustainable future. - Abstract: Biofuels produced from renewable energy biomass are playing a more significant role because of the environmental problems resulting from the use of fossil fuels. However, a major problem with biofuel production is that despite the range of feedstock that can be used, raw material availability varies considerably. By combining a series of theories and methods, the research objective of this study is to determine the current developments and the future trends in biofuel feedstock. By combining technological paradigm theory with literature mining, it was found that biofuel feedstock production development followed a three-stage trajectory, which was in accordance with the traditional technological paradigm – the S-curve. This new curve can be divided into BFDP (biofuel feedstock development paradigm) competition, BFDP diffusion, and BFDP shift. The biofuel production diffusion velocity model showed that there has been constant growth from 2000, with the growth rate reaching a peak in 2008, after which time it began to drop. Biofuel production worldwide is expected to remain unchanged until 2030 when a paradigm shift is expected. This study also illustrates the results of our innovative procedure – a combination of the data analysis system and the technological paradigm theory – for the present biofuel feedstock soft path that will lead to this paradigm shift, with integrated biofuel production feedstock systems expected to be a significant new trend.

  5. GRB 110731A within the IGC paradigm

    Directory of Open Access Journals (Sweden)

    Primorac Daria

    2018-01-01

    Full Text Available Bright gamma-ray burst (GRB 110731A was simultaneously observed by Fermi and Swift observatories, with a follow up optical observation which inferred the redshift of z = 2.83. Thus, available data are spanning from optical to high energy (GeV emission. We analyze these data within the induced gravitational collapse (IGC paradigm, recently introduced to explain temporal coincidence of some long GRBs with type Ic supernovae. The case of binary-driven hypcrnova (BdHN assumes a close system, which starts as an evolved core - neutron star binary. After the core-collapse event, the new NS - black hole system is formed, emitting the GRB in the process. We performed the time-resolved and time-integrated analysis of the Fermi data. Preliminary results gave isotropic energy Eiso = 6.05 × 1053 erg and the total P-GRB energy of Ep–GRB = 3.7 × 1052 erg. At transparency point we found a Lorentz factor Γ ~ 2.17 × 103 laboratory radius of 8.33 x 1013 cm, P-GRB observed temperature of 168 keV and a baryon load B = 4.35 × 10-4. Simulated light-curve and prompt emission spectra showed the average circum burst medium density to be n ~ 0.03 particles per cm3. We reproduced the X-ray light-curve within the rest-frame of the source, finding the common late power-law behavior, with α = –1.22. Considering these results, we interpret GRB 110731A as a member of a BdHNe group.

  6. Nonalcoholic fatty liver disease: Evolving paradigms

    Science.gov (United States)

    Lonardo, Amedeo; Nascimbeni, Fabio; Maurantonio, Mauro; Marrazzo, Alessandra; Rinaldi, Luca; Adinolfi, Luigi Elio

    2017-01-01

    In the last years new evidence has accumulated on nonalcoholic fatty liver disease (NAFLD) challenging the paradigms that had been holding the scene over the previous 30 years. NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases. Conversely, focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach. NAFLD, which can be diagnosed with either non-invasive strategies or through liver biopsy, is a pathogenically complex and clinically heterogeneous disease. The existence of metabolic as opposed to genetic-associated disease, notably including ”lean NAFLD” has recently been recognized. Moreover, NAFLD is a systemic condition, featuring metabolic, cardiovascular and (hepatic/extra-hepatic) cancer risk. Among the clinico-laboratory features of NAFLD we discuss hyperuricemia, insulin resistance, atherosclerosis, gallstones, psoriasis and selected endocrine derangements. NAFLD is a precursor of type 2 diabetes (T2D) and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD. Finally, lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed. In conclusion, this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies, intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible. PMID:29085206

  7. Local seafood: rethinking the direct marketing paradigm

    Directory of Open Access Journals (Sweden)

    Joshua S. Stoll

    2015-06-01

    Full Text Available Faced with strict regulations, rising operational costs, depleted stocks, and competition from less expensive foreign imports, many fishers are pursuing new ways to market and sell their catch. Direct marketing arrangements can increase the ex-vessel value of seafood and profitability of operations for fishers by circumventing dominant wholesale chains of custody and capturing the premium that customers are willing to pay for local seafood. Our analysis goes beyond a paradigm that understands direct marketing arrangements as solely economic tools to consider how these emerging business configurations create a set of conditions that can result in increased bonding and bridging capital among fishers by incentivizing cooperation, communication, and information production and organization. To build our case, we report on the economic value being generated for fishers in a cooperatively owned and operated direct marketing arrangement in eastern North Carolina. Over the course of 2 years, fishers participating in the Walking Fish community-supported fishery received 33% more revenue for their catch compared to the average monthly ex-vessel price of finfish and shellfish landed in the surrounding region, and an additional 14% to 18% more per dollar by way of year-end profit sharing. We argue that these economic benefits create an incentive to participate, resulting in cooperation among fishers and increased communication skills that foster bonding and bridging capital that put fishers in a position to identify and respond to challenges that threaten the social-ecological resilience of the systems within which they operate. We suggest that "institutional starters" like these can play a critical role in increasing the resilience of social-ecological systems, including fisheries.

  8. Cooperate! A paradigm shift for health equity.

    Science.gov (United States)

    Chang, Wei-Ching; Fraser, Joy H

    2017-02-21

    The role of competition and cooperation in relation to the goal of health equity is examined in this paper. The authors explain why the win-lose mentality associated with avoidable competition is ethically questionable and less effective than cooperation in achieving positive outcomes, particularly as it relates to health and health equity. Competition, which differentiates winners from losers, often with the winner-takes-all reward system, inevitably leads to a few winners and many losers, resulting in social inequality, which, in turn, engenders and perpetuates health inequity.Competitive market-driven approaches to healthcare-brought about by capitalism, neo-liberalization, and globalization, based primarily on a competitive framework-are shown to have contributed to growing inequities with respect to the social determinants of health, and have undermined equal opportunity to access health care and achieve health equity. It is possible to redistribute income and wealth to reduce social inequality, but globalization poses increasing challenges to policy makers. John Stuart Mill provided a passionate, philosophical defense of cooperatives, followed by Karl Polanyi who offered an insightful critique of both state socialism and especially the self-regulating market, thereby opening up the cooperative way of shaping the future. We cite Hannah Arendt's "the banality of evil" to characterize the tragic concept of "ethical fading" witnessed in business and everyday life all over the world, often committed (without thinking and reflecting) by ordinary people under competitive pressures.To promote equity in health for all, we recommend the adoption of a radically new cooperation paradigm, applied whenever possible, to everything in our daily lives.

  9. Electromagnetic servoing-a new tracking paradigm.

    Science.gov (United States)

    Reichl, Tobias; Gardiazabal, José; Navab, Nassir

    2013-08-01

    Electromagnetic (EM) tracking is highly relevant for many computer assisted interventions. This is in particular due to the fact that the scientific community has not yet developed a general solution for tracking of flexible instruments within the human body. Electromagnetic tracking solutions are highly attractive for minimally invasive procedures, since they do not require line of sight. However, a major problem with EM tracking solutions is that they do not provide uniform accuracy throughout the tracking volume and the desired, highest accuracy is often only achieved close to the center of tracking volume. In this paper, we present a solution to the tracking problem, by mounting an EM field generator onto a robot arm. Proposing a new tracking paradigm, we take advantage of the electromagnetic tracking to detect the sensor within a specific sub-volume, with known and optimal accuracy. We then use the more accurate and robust robot positioning for obtaining uniform accuracy throughout the tracking volume. Such an EM servoing methodology guarantees optimal and uniform accuracy, by allowing us to always keep the tracked sensor close to the center of the tracking volume. In this paper, both dynamic accuracy and accuracy distribution within the tracking volume are evaluated using optical tracking as ground truth. In repeated evaluations, the proposed method was able to reduce the overall error from 6.64±7.86 mm to a significantly improved accuracy of 3.83±6.43 mm. In addition, the combined system provides a larger tracking volume, which is only limited by the reach of the robot and not the much smaller tracking volume defined by the magnetic field generator.

  10. Autonomous vehicles: from paradigms to technology

    Science.gov (United States)

    Ionita, Silviu

    2017-10-01

    Mobility is a basic necessity of contemporary society and it is a key factor in global economic development. The basic requirements for the transport of people and goods are: safety and duration of travel, but also a number of additional criteria are very important: energy saving, pollution, passenger comfort. Due to advances in hardware and software, automation has penetrated massively in transport systems both on infrastructure and on vehicles, but man is still the key element in vehicle driving. However, the classic concept of ‘human-in-the-loop’ in terms of ‘hands on’ in driving the cars is competing aside from the self-driving startups working towards so-called ‘Level 4 autonomy’, which is defined as “a self-driving system that does not requires human intervention in most scenarios”. In this paper, a conceptual synthesis of the autonomous vehicle issue is made in connection with the artificial intelligence paradigm. It presents a classification of the tasks that take place during the driving of the vehicle and its modeling from the perspective of traditional control engineering and artificial intelligence. The issue of autonomous vehicle management is addressed on three levels: navigation, movement in traffic, respectively effective maneuver and vehicle dynamics control. Each level is then described in terms of specific tasks, such as: route selection, planning and reconfiguration, recognition of traffic signs and reaction to signaling and traffic events, as well as control of effective speed, distance and direction. The approach will lead to a better understanding of the way technology is moving when talking about autonomous cars, smart/intelligent cars or intelligent transport systems. Keywords: self-driving vehicle, artificial intelligence, deep learning, intelligent transport systems.

  11. GRB 110731A within the IGC paradigm

    Science.gov (United States)

    Primorac, Daria; Ruffini, Remo; Pisani, Giovanni Battista; Aimuratov, Yerlan; Biancol, Carlo Luciano; Karlica, Mile; Melon Fuksman, Julio David; Moradi, Rahim; Muccino, Marco; Penacchioni, Ana Virginia; Rueda, Jorge Armando; Wang, Yu

    2018-01-01

    Bright gamma-ray burst (GRB) 110731A was simultaneously observed by Fermi and Swift observatories, with a follow up optical observation which inferred the redshift of z = 2.83. Thus, available data are spanning from optical to high energy (GeV) emission. We analyze these data within the induced gravitational collapse (IGC) paradigm, recently introduced to explain temporal coincidence of some long GRBs with type Ic supernovae. The case of binary-driven hypcrnova (BdHN) assumes a close system, which starts as an evolved core - neutron star binary. After the core-collapse event, the new NS - black hole system is formed, emitting the GRB in the process. We performed the time-resolved and time-integrated analysis of the Fermi data. Preliminary results gave isotropic energy Eiso = 6.05 × 1053 erg and the total P-GRB energy of Ep-GRB = 3.7 × 1052 erg. At transparency point we found a Lorentz factor Γ 2.17 × 103 laboratory radius of 8.33 x 1013 cm, P-GRB observed temperature of 168 keV and a baryon load B = 4.35 × 10-4. Simulated light-curve and prompt emission spectra showed the average circum burst medium density to be n 0.03 particles per cm3. We reproduced the X-ray light-curve within the rest-frame of the source, finding the common late power-law behavior, with α = -1.22. Considering these results, we interpret GRB 110731A as a member of a BdHNe group.

  12. Periods and Nori motives

    CERN Document Server

    Huber, Annette

    2017-01-01

    This book casts the theory of periods of algebraic varieties in the natural setting of Madhav Nori’s abelian category of mixed motives. It develops Nori’s approach to mixed motives from scratch, thereby filling an important gap in the literature, and then explains the connection of mixed motives to periods, including a detailed account of the theory of period numbers in the sense of Kontsevich-Zagier and their structural properties. Period numbers are central to number theory and algebraic geometry, and also play an important role in other fields such as mathematical physics. There are long-standing conjectures about their transcendence properties, best understood in the language of cohomology of algebraic varieties or, more generally, motives. Readers of this book will discover that Nori’s unconditional construction of an abelian category of motives (over fields embeddable into the complex numbers) is particularly well suited for this purpose. Notably, Kontsevich's formal period algebra represents a to...

  13. Contemporary paradigms for research related to women's mental health.

    Science.gov (United States)

    Doucet, Shelley Anne; Letourneau, Nicole Lyn; Stoppard, Janet M

    2010-04-01

    Mental health problems are serious health concerns that affect women across diverse settings internationally. Knowledge of this population historically has been informed by research using a positivist approach. This article is a critical examination of contemporary paradigms for research related to women's mental health. We begin the article with an introduction to women's mental health, followed by an overview of the postpositivist, critical theory, and constructivist paradigms. We then present a critical examination of the benefits and limitations of these paradigms in relation to the study of women's mental health. We conclude with implications for research and practice.

  14. Innovation Policy Development and the Emergence of New Innovation Paradigms

    DEFF Research Database (Denmark)

    Tanev, Stoyan; Knudsen, Mette Præst; Bisgaard, Tanja

    2011-01-01

    The objective of the present article is to discuss innovation policy issues related to three emerging innovation paradigms: user-driven innovation, open innovation, and value cocreation. It provides a summary of insights based on innovation policy practices and challenges in Denmark. The choice...... of Danish innovation policy practices is not accidental. In 2008 Denmark implemented 40 different national innovation programs by allocating about 400 million euros. Since the three emerging paradigms have become globally relevant, the discussion of Danish policy development challenges and practices...... is expected to be insightful for innovation experts from other developed countries that are currently dealing with the adoption of these paradigms....

  15. A flow paradigm in heavy-ion collisions

    Science.gov (United States)

    Yan, Li

    2018-04-01

    The success of hydrodynamics in high energy heavy-ion collisions leads to a flow paradigm, to understand the observed features of harmonic flow in terms of the medium collective expansion with respect to initial state geometrical properties. In this review, we present some essential ingredients in the flow paradigm, including the hydrodynamic modeling, the characterization of initial state geometry and the medium response relations. The extension of the flow paradigm to small colliding systems is also discussed. Supported by Natural Sciences and Engineering Research Council of Canada

  16. Clinical fMRI of language function in aphasic patients: Reading paradigm successful, while word generation paradigm fails

    Energy Technology Data Exchange (ETDEWEB)

    Engstroem, Maria; Landtblom, Anne-Marie; Ragnehed, Mattias; Lundberg, Peter (Center for Medical Image Science and Visualization (CMIV), Linkoeping Univ., Linkoeping (Sweden)), e-mail: maria.engstrom@liu.se; Karlsson, Marie; Crone, Marie (Dept. of Clinical and Experimental Medicine/Logopedics, Linkoeping Univ., Linkoeping (Sweden)); Antepohl, Wolfram (Dept. of Clinical and Experimental Medicine/Rehabilitation, Linkoeping Univ., Linkoeping (Sweden))

    2010-07-15

    Background: In fMRI examinations, it is very important to select appropriate paradigms assessing the brain function of interest. In addition, the patients' ability to perform the required cognitive tasks during fMRI must be taken into account. Purpose: To evaluate two language paradigms, word generation and sentence reading for their usefulness in examinations of aphasic patients and to make suggestions for improvements of clinical fMRI. Material and Methods: Five patients with aphasia after stroke or trauma sequelae were examined by fMRI. The patients' language ability was screened by neurolinguistic tests and elementary pre-fMRI language tests. Results: The sentence-reading paradigm succeeded to elicit adequate language-related activation in perilesional areas whereas the word generation paradigm failed. These findings were consistent with results on the behavioral tests in that all patients showed very poor performance in phonemic fluency, but scored well above mean at a reading comprehension task. Conclusion: The sentence-reading paradigm is appropriate to assess language function in this patient group, while the word-generation paradigm seems to be inadequate. In addition, it is crucial to use elementary pre-fMRI language tests to guide the fMRI paradigm decision.

  17. Clinical fMRI of language function in aphasic patients: Reading paradigm successful, while word generation paradigm fails

    International Nuclear Information System (INIS)

    Engstroem, Maria; Landtblom, Anne-Marie; Ragnehed, Mattias; Lundberg, Peter; Karlsson, Marie; Crone, Marie; Antepohl, Wolfram

    2010-01-01

    Background: In fMRI examinations, it is very important to select appropriate paradigms assessing the brain function of interest. In addition, the patients' ability to perform the required cognitive tasks during fMRI must be taken into account. Purpose: To evaluate two language paradigms, word generation and sentence reading for their usefulness in examinations of aphasic patients and to make suggestions for improvements of clinical fMRI. Material and Methods: Five patients with aphasia after stroke or trauma sequelae were examined by fMRI. The patients' language ability was screened by neurolinguistic tests and elementary pre-fMRI language tests. Results: The sentence-reading paradigm succeeded to elicit adequate language-related activation in perilesional areas whereas the word generation paradigm failed. These findings were consistent with results on the behavioral tests in that all patients showed very poor performance in phonemic fluency, but scored well above mean at a reading comprehension task. Conclusion: The sentence-reading paradigm is appropriate to assess language function in this patient group, while the word-generation paradigm seems to be inadequate. In addition, it is crucial to use elementary pre-fMRI language tests to guide the fMRI paradigm decision.

  18. Solution Methods for the Periodic Petrol Station Replenishment Problem

    OpenAIRE

    C Triki

    2013-01-01

    In this paper we introduce the Periodic Petrol Station Replenishment Problem (PPSRP) over a T-day planning horizon and describe four heuristic methods for its solution. Even though all the proposed heuristics belong to the common partitioning-then-routing paradigm, they differ in assigning the stations to each day of the horizon. The resulting daily routing problems are then solved exactly until achieving optimalization. Moreover, an improvement procedure is also developed with the aim of ens...

  19. Mean-periodic functions

    Directory of Open Access Journals (Sweden)

    Carlos A. Berenstein

    1980-01-01

    Full Text Available We show that any mean-periodic function f can be represented in terms of exponential-polynomial solutions of the same convolution equation f satisfies, i.e., u∗f=0(μ∈E′(ℝn. This extends to n-variables the work of L. Schwartz on mean-periodicity and also extends L. Ehrenpreis' work on partial differential equations with constant coefficients to arbitrary convolutors. We also answer a number of open questions about mean-periodic functions of one variable. The basic ingredient is our work on interpolation by entire functions in one and several complex variables.

  20. Moments, Mixed Methods, and Paradigm Dialogs

    Science.gov (United States)

    Denzin, Norman K.

    2010-01-01

    I reread the 50-year-old history of the qualitative inquiry that calls for triangulation and mixed methods. I briefly visit the disputes within the mixed methods community asking how did we get to where we are today, the period of mixed-multiple-methods advocacy, and Teddlie and Tashakkori's third methodological moment. (Contains 10 notes.)