New quantum criticality revealed under pressure

International Nuclear Information System (INIS)

Watanabe, Shinji; Miyake, Kazumasa

2017-01-01

Unconventional quantum critical phenomena observed in Yb-based periodic crystals such as YbRh_2Si_2 and β-YbAlB_4 have been one of the central issues in strongly correlated electron systems. The common criticality has been discovered in the quasicrystal Yb_1_5Au_5_1Al_3_4, which surprisingly persists under pressure at least up to P = 1.5 GPa. The T/H scaling where the magnetic susceptibility can be expressed as a single scaling function of the ratio of the temperature T to the magnetic field H has been discovered in the quasicrystal, which is essentially the same as that observed in β-YbAlB_4. Recently, the T/H scaling as well as the common criticality has also been observed even in the approximant crystal Yb_1_4Au_5_1Al_3_5 under pressure. The theory of critical Yb-valence fluctuation gives a natural explanation for these striking phenomena in a unified way. (author)

A microarray of ubiquitylated proteins for profiling deubiquitylase activity reveals the critical roles of both chain and substrate.

Science.gov (United States)

Loch, Christian M; Strickler, James E

2012-11-01

Substrate ubiquitylation is a reversible process critical to cellular homeostasis that is often dysregulated in many human pathologies including cancer and neurodegeneration. Elucidating the mechanistic details of this pathway could unlock a large store of information useful to the design of diagnostic and therapeutic interventions. Proteomic approaches to the questions at hand have generally utilized mass spectrometry (MS), which has been successful in identifying both ubiquitylation substrates and profiling pan-cellular chain linkages, but is generally unable to connect the two. Interacting partners of the deubiquitylating enzymes (DUBs) have also been reported by MS, although substrates of catalytically competent DUBs generally cannot be. Where they have been used towards the study of ubiquitylation, protein microarrays have usually functioned as platforms for the identification of substrates for specific E3 ubiquitin ligases. Here, we report on the first use of protein microarrays to identify substrates of DUBs, and in so doing demonstrate the first example of microarray proteomics involving multiple (i.e., distinct, sequential and opposing) enzymatic activities. This technique demonstrates the selectivity of DUBs for both substrate and type (mono- versus poly-) of ubiquitylation. This work shows that the vast majority of DUBs are monoubiquitylated in vitro, and are incapable of removing this modification from themselves. This work also underscores the critical role of utilizing both ubiquitin chains and substrates when attempting to characterize DUBs. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics. Copyright © 2012 Elsevier B.V. All rights reserved.

The role of visualisation in developing critical thinking in mathematics

African Journals Online (AJOL)

Research has been conducted on the role and importance of visualisation in many fields, including psychology, but very little has been done to extend its role to mathematics education in particular. Furthermore, much research has been done on the importance of critical thinking. However, to date not much has been done ...

The Arabidopsis nox mutant lacking carotene hydroxylase activity reveals a critical role for xanthophylls in photosystem I biogenesis.

Science.gov (United States)

Dall'Osto, Luca; Piques, Maria; Ronzani, Michela; Molesini, Barbara; Alboresi, Alessandro; Cazzaniga, Stefano; Bassi, Roberto

2013-02-01

Carotenes, and their oxygenated derivatives xanthophylls, are essential components of the photosynthetic apparatus. They contribute to the assembly of photosynthetic complexes and participate in light absorption and chloroplast photoprotection. Here, we studied the role of xanthophylls, as distinct from that of carotenes, by characterizing a no xanthophylls (nox) mutant of Arabidopsis thaliana, which was obtained by combining mutations targeting the four carotenoid hydroxylase genes. nox plants retained α- and β-carotenes but were devoid in xanthophylls. The phenotype included depletion of light-harvesting complex (LHC) subunits and impairment of nonphotochemical quenching, two effects consistent with the location of xanthophylls in photosystem II antenna, but also a decreased efficiency of photosynthetic electron transfer, photosensitivity, and lethality in soil. Biochemical analysis revealed that the nox mutant was specifically depleted in photosystem I function due to a severe deficiency in PsaA/B subunits. While the stationary level of psaA/B transcripts showed no major differences between genotypes, the stability of newly synthesized PsaA/B proteins was decreased and translation of psaA/B mRNA was impaired in nox with respect to wild-type plants. We conclude that xanthophylls, besides their role in photoprotection and LHC assembly, are also needed for photosystem I core translation and stability, thus making these compounds indispensable for autotrophic growth.

Critical Role of Monoclinic Polarization Rotation in High-Performance Perovskite Piezoelectric Materials.

Science.gov (United States)

Liu, Hui; Chen, Jun; Fan, Longlong; Ren, Yang; Pan, Zhao; Lalitha, K V; Rödel, Jürgen; Xing, Xianran

2017-07-07

High-performance piezoelectric materials constantly attract interest for both technological applications and fundamental research. The understanding of the origin of the high-performance piezoelectric property remains a challenge mainly due to the lack of direct experimental evidence. We perform in situ high-energy x-ray diffraction combined with 2D geometry scattering technology to reveal the underlying mechanism for the perovskite-type lead-based high-performance piezoelectric materials. The direct structural evidence reveals that the electric-field-driven continuous polarization rotation within the monoclinic plane plays a critical role to achieve the giant piezoelectric response. An intrinsic relationship between the crystal structure and piezoelectric performance in perovskite ferroelectrics has been established: A strong tendency of electric-field-driven polarization rotation generates peak piezoelectric performance and vice versa. Furthermore, the monoclinic M_{A} structure is the key feature to superior piezoelectric properties as compared to other structures such as monoclinic M_{B}, rhombohedral, and tetragonal. A high piezoelectric response originates from intrinsic lattice strain, but little from extrinsic domain switching. The present results will facilitate designing high-performance perovskite piezoelectric materials by enhancing the intrinsic lattice contribution with easy and continuous polarization rotation.

Role strain among male RNs in the critical care setting: Perceptions of an unfriendly workplace.

Science.gov (United States)

Carte, Nicholas S; Williams, Collette

2017-12-01

Traditionally, nursing has been a female-dominated profession. Men employed as registered nurses have been in the minority and little is known about the experiences of this demographic. The purpose of this descriptive, quantitative study was to understand the relationship between the variables of demographics and causes of role strain among male nurses in critical care settings. The Sherrod Role Strain Scale assesses role strain within the context of role conflict, role overload, role ambiguity and role incongruity. Data analysis of the results included descriptive and inferential statistics. Inferential statistics involved the use of repeated measures ANOVA testing for significant difference in the causes of role strain between male nurses employed in critical care settings and a post hoc comparison of specific demographic data using multivariate analyses of variance (MANOVAs). Data from 37 male nurses in critical care settings from the northeast of the United States were used to calculate descriptive statistics standard deviation, mean of the data analysis and results of the repeated ANOVA and the post hoc secondary MANOVA analysis. The descriptive data showed that all participants worked full-time. There was an even split from those participants who worked day shift (46%) vs. night shift (43%), most the participants indicated they had 15 years or more experience as an registered nurse (54%). Significant findings of this study include two causes of role strain in male nurses employed in critical care settings which are: role ambiguity and role overload based on ethnicity. Consistent with previous research findings, the results of this study suggest that male registered nurses employed in critical care settings do experience role strain. The two main causes of role strain in male nurses are role ambiguity and role overload. Copyright © 2017. Published by Elsevier Ltd.

Role, perspective and knowledge of Iranian critical care nurses about breaking bad news.

Science.gov (United States)

Imanipour, Masoomeh; Karim, Zahra; Bahrani, Naser

2016-05-01

Given the issue of caring critically ill patients, nurses are involved in the process of breaking bad news in critical care units, while little research has been conducted on this challenging issue. The purpose of this study was to determine the role, perspective and knowledge of Iranian critical care nurses regarding breaking bad news. This descriptive study was conducted on a sample of 160 nurses working in critical care units of hospitals affiliated to Tehran University of Medical Sciences. Stratified and quota sampling methods were used. The data collection tool was a four-part questionnaire with validity and reliability confirmed via content validity and test-retest, respectively. The study showed that most critical care nurses were involved in breaking bad news, with different roles. The majority of participants (91.2%) had a positive attitude towards involvement of nurses in breaking bad news. In this study, 78.8% of nurses had moderate knowledge about how to break bad news, and only a few had good level of knowledge (16.2%). According to the findings, while critical care nurses took different roles in the process of breaking bad news and they had positive attitude towards participation in this process, yet their knowledge about this process was inadequate. Thus, designing educational programmes to enhance critical care nurses' knowledge and skills in this area seems necessary. Copyright © 2015 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

The role of intergenerational similarity and parenting in adolescent self-criticism: An actor-partner interdependence model.

Science.gov (United States)

Bleys, Dries; Soenens, Bart; Boone, Liesbet; Claes, Stephan; Vliegen, Nicole; Luyten, Patrick

2016-06-01

Research investigating the development of adolescent self-criticism has typically focused on the role of either parental self-criticism or parenting. This study used an actor-partner interdependence model to examine an integrated theoretical model in which achievement-oriented psychological control has an intervening role in the relation between parental and adolescent self-criticism. Additionally, the relative contribution of both parents and the moderating role of adolescent gender were examined. Participants were 284 adolescents (M = 14 years, range = 12-16 years) and their parents (M = 46 years, range = 32-63 years). Results showed that only maternal self-criticism was directly related to adolescent self-criticism. However, both parents' achievement-oriented psychological control had an intervening role in the relation between parent and adolescent self-criticism in both boys and girls. Moreover, one parent's achievement-oriented psychological control was not predicted by the self-criticism of the other parent. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

The critical role of myostatin in differentiation of sheep myoblasts

Energy Technology Data Exchange (ETDEWEB)

Liu, Chenxi [College of Life Science and Technology, Xinjiang University, Urumqi (China); Xinjiang Laboratory of Animal Biotechnology, Urumqi (China); Li, Wenrong; Zhang, Xuemei; Zhang, Ning; He, Sangang; Huang, Juncheng [Xinjiang Laboratory of Animal Biotechnology, Urumqi (China); Laboratory of Grass-fed Animal Genetics, Breeding and Reproduction of Ministry of Agriculture, Urumqi (China); Animal Biotechnological Research Center, Xinjiang Academy of Animal Science, Urumqi (China); Ge, Yubin [The State Engineering Laboratory of AIDS Vaccine, College of Life Science, Jilin University, Changchun (China); Liu, Mingjun, E-mail: xjlmj2004@yahoo.com.cn [Xinjiang Laboratory of Animal Biotechnology, Urumqi (China); Laboratory of Grass-fed Animal Genetics, Breeding and Reproduction of Ministry of Agriculture, Urumqi (China); Animal Biotechnological Research Center, Xinjiang Academy of Animal Science, Urumqi (China)

2012-06-08

Highlights: Black-Right-Pointing-Pointer Identification of the effective and specific shRNA to knockdown MSTN. Black-Right-Pointing-Pointer Overexpression of MSTN reversibly suppressed myogenic differentiation. Black-Right-Pointing-Pointer shRNA knockdown of endogenous MSTN promoted ovine myoblast differentiation. Black-Right-Pointing-Pointer MSTN inhibits myogenic differentiation through down-regulation of MyoD and Myogenin and up-regulation of Smad3. Black-Right-Pointing-Pointer Provides a promise for the generation of transgenic sheep to improve meat productivity. -- Abstract: Myostatin [MSTN, also known as growth differentiation factor 8 (GDF8)], is an inhibitor of skeletal muscle growth. Blockade of MSTN function has been reported to result in increased muscle mass in mice. However, its role in myoblast differentiation in farm animals has not been determined. In the present study, we sought to determine the role of MSTN in the differentiation of primary sheep myoblasts. We found that ectopic overexpression of MSTN resulted in lower fusion index in sheep myoblasts, which indicated the repression of myoblast differentiation. This phenotypic change was reversed by shRNA knockdown of the ectopically expressed MSTN in the cells. In contrast, shRNA knockdown of the endogenous MSTN resulted in induction of myogenic differentiation. Additional studies revealed that the induction of differentiation by knocking down the ectopically or endogenously expressed MSTN was accompanied by up-regulation of MyoD and myogenin, and down-regulation of Smad3. Our results demonstrate that MSTN plays critical role in myoblast differentiation in sheep, analogous to that in mice. This study also suggests that shRNA knockdown of MSTN could be a potentially promising approach to improve sheep muscle growth, so as to increase meat productivity.

The critical role of myostatin in differentiation of sheep myoblasts

International Nuclear Information System (INIS)

Liu, Chenxi; Li, Wenrong; Zhang, Xuemei; Zhang, Ning; He, Sangang; Huang, Juncheng; Ge, Yubin; Liu, Mingjun

2012-01-01

Highlights: ► Identification of the effective and specific shRNA to knockdown MSTN. ► Overexpression of MSTN reversibly suppressed myogenic differentiation. ► shRNA knockdown of endogenous MSTN promoted ovine myoblast differentiation. ► MSTN inhibits myogenic differentiation through down-regulation of MyoD and Myogenin and up-regulation of Smad3. ► Provides a promise for the generation of transgenic sheep to improve meat productivity. -- Abstract: Myostatin [MSTN, also known as growth differentiation factor 8 (GDF8)], is an inhibitor of skeletal muscle growth. Blockade of MSTN function has been reported to result in increased muscle mass in mice. However, its role in myoblast differentiation in farm animals has not been determined. In the present study, we sought to determine the role of MSTN in the differentiation of primary sheep myoblasts. We found that ectopic overexpression of MSTN resulted in lower fusion index in sheep myoblasts, which indicated the repression of myoblast differentiation. This phenotypic change was reversed by shRNA knockdown of the ectopically expressed MSTN in the cells. In contrast, shRNA knockdown of the endogenous MSTN resulted in induction of myogenic differentiation. Additional studies revealed that the induction of differentiation by knocking down the ectopically or endogenously expressed MSTN was accompanied by up-regulation of MyoD and myogenin, and down-regulation of Smad3. Our results demonstrate that MSTN plays critical role in myoblast differentiation in sheep, analogous to that in mice. This study also suggests that shRNA knockdown of MSTN could be a potentially promising approach to improve sheep muscle growth, so as to increase meat productivity.

Maximizing Team Performance: The Critical Role of the Nurse Leader.

Science.gov (United States)

Manges, Kirstin; Scott-Cawiezell, Jill; Ward, Marcia M

2017-01-01

Facilitating team development is challenging, yet critical for ongoing improvement across healthcare settings. The purpose of this exemplary case study is to examine the role of nurse leaders in facilitating the development of a high-performing Change Team in implementing a patient safety initiative (TeamSTEPPs) using the Tuckman Model of Group Development as a guiding framework. The case study is the synthesis of 2.5 years of critical access hospital key informant interviews (n = 50). Critical juncture points related to team development and key nurse leader actions are analyzed, suggesting that nurse leaders are essential to maximize clinical teams' performance. © 2016 Wiley Periodicals, Inc.

A critical role of hypocretin deficiency in pregnancy.

Science.gov (United States)

Bastianini, Stefano; Berteotti, Chiara; Lo Martire, Viviana; Silvani, Alessandro; Zoccoli, Giovanna

2014-04-01

Hypocretin/orexin peptides are known for their role in the control of the wake–sleep cycle and narcolepsy–cataplexy pathophysiology. Recent studies suggested that hypocretin peptides also have a role in pregnancy. We tested this hypothesis by conducting a retrospective analysis on pregnancy complications in two different mouse models of hypocretin deficiency. We recorded 85 pregnancies of mice lacking either hypocretin peptides (knockout) or hypocretin-releasing neurons (transgenic) and their wild-type controls. Pregnancy was associated with unexplained dam death before delivery in 3/15 pregnancies in knockout mice, and in 3/23 pregnancies in transgenic mice. No casualties occurred in wild-type pregnant dams (P hypocretin-deficient mice as a whole). Hypocretin deficiency did not impact either on litter size or the number of weaned pups per litter. These data provide preliminary evidence of a critical role of hypocretin deficiency in pregnancy.

Some Thoughts on the Role of the Critical Intellectual in Contemporary Germany

Directory of Open Access Journals (Sweden)

Erich Steiner

2005-08-01

Full Text Available The paper starts by relating the notion of the "critical intellectual" to the notion of "agent of social change" on the one hand, and to other potential types of agents of change on the other: women in revolt, artists, exiles and queer agencies. Proceeding to a brief characterisation of the socio-cultural and political context "Germany", we shall explore some meanings of attributes such as post-modern and consumer for contemporary German society and culture, arguing that these are cultural and economic terms, which denote current forms of expression for what continues to be a capitalist economy and a bourgeois democracy. One recurrent question will be what the contours might be of the figure of the "critical intellectual" under present day conditions. This is followed by a brief sketch of the meanings of "kritische(r Intellektuelle(r" in a historical ("geistesgeschichtlicher" perspective, mainly from the enlightenment onwards. We shall move on to a methodologically very different, but complementary, perspective, which is the consideration of current usage of the term with the help of large-scale electronic corpora of spoken language and an on-line search on the web. As we shall see, an important share and quality of the relevant meanings of a term lies in current usage, which may or may not be directly related to what we know from the history of ideas and/ or etymology. I shall then use examples from my own professional field of work for an exploration of what the role of a critical intellectual in a German context might be, discussing the field of natural language technologies. These examples will illustrate the fact that such a role has to involve participation in, rather than exclusively detached contemplation of, the sphere of production. They will also show that the role of the critical intellectual is, indeed, a locus of contestation in several respects. We finally broaden our perspective into a wider set of questions relating to the role

Developmental Ethanol Exposure Causes Reduced Feeding and Reveals a Critical Role for Neuropeptide F in Survival

Science.gov (United States)

Guevara, Amanda; Gates, Hillary; Urbina, Brianna; French, Rachael

2018-01-01

Food intake is necessary for survival, and natural reward circuitry has evolved to help ensure that animals ingest sufficient food to maintain development, growth, and survival. Drugs of abuse, including alcohol, co-opt the natural reward circuitry in the brain, and this is a major factor in the reinforcement of drug behaviors leading to addiction. At the junction of these two aspects of reward are alterations in feeding behavior due to alcohol consumption. In particular, developmental alcohol exposure (DAE) results in a collection of physical and neurobehavioral disorders collectively referred to as Fetal Alcohol Spectrum Disorder (FASD). The deleterious effects of DAE include intellectual disabilities and other neurobehavioral changes, including altered feeding behaviors. Here we use Drosophila melanogaster as a genetic model organism to study the effects of DAE on feeding behavior and the expression and function of Neuropeptide F. We show that addition of a defined concentration of ethanol to food leads to reduced feeding at all stages of development. Further, genetic conditions that reduce or eliminate NPF signaling combine with ethanol exposure to further reduce feeding, and the distribution of NPF is altered in the brains of ethanol-supplemented larvae. Most strikingly, we find that the vast majority of flies with a null mutation in the NPF receptor die early in larval development when reared in ethanol, and provide evidence that this lethality is due to voluntary starvation. Collectively, we find a critical role for NPF signaling in protecting against altered feeding behavior induced by developmental ethanol exposure. PMID:29623043

How to Identify Negative Attitudes towards Inclusive Education: Critical Discourse Analysis of Russian Transcripts Using Role and Reference Grammar

Directory of Open Access Journals (Sweden)

Mariia Rubtcova

2016-09-01

Full Text Available This paper presents the Role and Reference Grammar (RRG analysis that aims to reveal possibilities required for carrying out the interdisciplinary research development within Critical Discourse Analysis (CDA. It takes a closer look at conflicts, considering the example of a conflict situation occurred in reaction to the opening of the inclusive academic programme at one of St. Petersburg’s secondary schools. Role and Reference Grammar application demonstrates that the use of different verb types and macroroles has led to the various interpretations. These findings confirm that RRG could influence the increase of objectivity of the transcript analysis in qualitative social research. RRG provides new information which in combination with other methods can help us to understand the positions of participants involved into conflicts

Universal role of correlation entropy in critical phenomena

International Nuclear Information System (INIS)

Gu Shijian; Sun Changpu; Lin Haiqing

2008-01-01

In statistical physics, if we divide successively an equilibrium system into two parts, we will face a situation that, to a certain length ξ, the physics of a subsystem is no longer the same as the original one. The extensive property of the thermal entropy S(A union B) = S(A) + S(B) is then violated. This observation motivates us to introduce a concept of correlation entropy between two points, as measured by the mutual information in information theory, to study the critical phenomena. A rigorous relation is established to display some drastic features of the non-vanishing correlation entropy of a subsystem formed by any two distant particles with long-range correlation. This relation actually indicates a universal role played by the correlation entropy for understanding the critical phenomena. We also verify these analytical studies in terms of two well-studied models for both the thermal and quantum phase transitions: the two-dimensional Ising model and the one-dimensional transverse-field Ising model. Therefore, the correlation entropy provides us with a new physical intuition of the critical phenomena from the point of view of information theory

What's My Lane? Identifying the State Government Role in Critical Infrastructure Protection

OpenAIRE

Donnelly, Timothy S.

2012-01-01

Approved for public release; distribution is unlimited What constitutes an effective Critical Infrastructure and Key Resources (CIKR) protection program for Massachusetts This study evaluates existing literature regarding CIKR to extrapolate an infrastructure protection role for Massachusetts. By reviewing historical events and government strategies regarding infrastructure protection, Chapters I and II will provide scope and context for issues surrounding critical infrastructure. Chapter ...

A novel immunotoxin reveals a new role for CD321 in endothelial cells.

Directory of Open Access Journals (Sweden)

Takeshi Fukuhara

Full Text Available There are currently several antibody therapies that directly target tumors, and antibody-drug conjugates represent a novel moiety as next generation therapeutics. Here, we used a unique screening probe, DT3C, to identify functional antibodies that recognized surface molecules and functional epitopes, and which provided toxin delivery capability. Accordingly, we generated the 90G4 antibody, which induced DT3C-dependent cytotoxicity in endothelial cells. Molecular analysis revealed that 90G4 recognized CD321, a protein localized at tight junctions. Although CD321 plays a pivotal role in inflammation and lymphocyte trans-endothelial migration, little is known about its mechanism of action in endothelial cells. Targeting of CD321 by the 90G4 immunotoxin induced cell death. Moreover, 90G4 immunotoxin caused cytotoxicity primarily in migratory endothelial cells, but not in those forming sheets, suggesting a critical role for CD321 in tumor angiogenesis. We also found that hypoxia triggered redistribution of CD321 to a punctate localization on the basal side of cells, resulting in functional impairment of tight junctions and increased motility. Thus, our findings raise the intriguing possibility that endothelial CD321 presented cellular localization in tight junction as well as multifunctional dynamics in several conditions, leading to illuminate the importance of widely-expressed CD321 as a potential target for antitumor therapy.

Critical thinking and the role of the clinical ultrasound tutor

International Nuclear Information System (INIS)

Edwards, Hazel

2006-01-01

As radiographers continue to extend their role and take on more procedures associated traditionally with radiologists, it is essential that their critical thinking abilities keep pace with the new practical skills they are learning. This is particularly important in ultrasound where student sonographers must master a number of new skills including the technical dexterity required to perform a scan, the ability to form and discard hypotheses when trying to interpret the image, and the communication of their findings as a written report. Interpreting the image and producing an accurate, appropriate report involves the higher level cognitive processes of analysis, synthesis and evaluation. In other words, the student sonographer must be able to think critically to become a successful practitioner. This paper attempts to define and discuss critical thinking, and considers a range of simple strategies that the clinical teacher of ultrasound can employ to help develop critical thinking skills in their students. These methods are appropriate for use not only by clinical teachers of ultrasound but for all teachers and mentors wishing to improve reasoning skills in their pupils

Isolation of Chromatin from Dysfunctional Telomeres Reveals an Important Role for Ring1b in NHEJ-Mediated Chromosome Fusions

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Cristina Bartocci

2014-05-01

Full Text Available When telomeres become critically short, DNA damage response factors are recruited at chromosome ends, initiating a cellular response to DNA damage. We performed proteomic isolation of chromatin fragments (PICh in order to define changes in chromatin composition that occur upon onset of acute telomere dysfunction triggered by depletion of the telomere-associated factor TRF2. This unbiased purification of telomere-associated proteins in functional or dysfunctional conditions revealed the dynamic changes in chromatin composition that take place at telomeres upon DNA damage induction. On the basis of our results, we describe a critical role for the polycomb group protein Ring1b in nonhomologous end-joining (NHEJ-mediated end-to-end chromosome fusions. We show that cells with reduced levels of Ring1b have a reduced ability to repair uncapped telomeric chromatin. Our data represent an unbiased isolation of chromatin undergoing DNA damage and are a valuable resource to map the changes in chromatin composition in response to DNA damage activation.

The Arabidopsis nox Mutant Lacking Carotene Hydroxylase Activity Reveals a Critical Role for Xanthophylls in Photosystem I Biogenesis[C][W

Science.gov (United States)

Dall’Osto, Luca; Piques, Maria; Ronzani, Michela; Molesini, Barbara; Alboresi, Alessandro; Cazzaniga, Stefano; Bassi, Roberto

2013-01-01

Carotenes, and their oxygenated derivatives xanthophylls, are essential components of the photosynthetic apparatus. They contribute to the assembly of photosynthetic complexes and participate in light absorption and chloroplast photoprotection. Here, we studied the role of xanthophylls, as distinct from that of carotenes, by characterizing a no xanthophylls (nox) mutant of Arabidopsis thaliana, which was obtained by combining mutations targeting the four carotenoid hydroxylase genes. nox plants retained α- and β-carotenes but were devoid in xanthophylls. The phenotype included depletion of light-harvesting complex (LHC) subunits and impairment of nonphotochemical quenching, two effects consistent with the location of xanthophylls in photosystem II antenna, but also a decreased efficiency of photosynthetic electron transfer, photosensitivity, and lethality in soil. Biochemical analysis revealed that the nox mutant was specifically depleted in photosystem I function due to a severe deficiency in PsaA/B subunits. While the stationary level of psaA/B transcripts showed no major differences between genotypes, the stability of newly synthesized PsaA/B proteins was decreased and translation of psaA/B mRNA was impaired in nox with respect to wild-type plants. We conclude that xanthophylls, besides their role in photoprotection and LHC assembly, are also needed for photosystem I core translation and stability, thus making these compounds indispensable for autotrophic growth. PMID:23396829

Bcl2-associated Athanogene 3 Interactome Analysis Reveals a New Role in Modulating Proteasome Activity*

Science.gov (United States)

Chen, Ying; Yang, Li-Na; Cheng, Li; Tu, Shun; Guo, Shu-Juan; Le, Huang-Ying; Xiong, Qian; Mo, Ran; Li, Chong-Yang; Jeong, Jun-Seop; Jiang, Lizhi; Blackshaw, Seth; Bi, Li-Jun; Zhu, Heng; Tao, Sheng-Ce; Ge, Feng

2013-01-01

Bcl2-associated athanogene 3 (BAG3), a member of the BAG family of co-chaperones, plays a critical role in regulating apoptosis, development, cell motility, autophagy, and tumor metastasis and in mediating cell adaptive responses to stressful stimuli. BAG3 carries a BAG domain, a WW domain, and a proline-rich repeat (PXXP), all of which mediate binding to different partners. To elucidate BAG3's interaction network at the molecular level, we employed quantitative immunoprecipitation combined with knockdown and human proteome microarrays to comprehensively profile the BAG3 interactome in humans. We identified a total of 382 BAG3-interacting proteins with diverse functions, including transferase activity, nucleic acid binding, transcription factors, proteases, and chaperones, suggesting that BAG3 is a critical regulator of diverse cellular functions. In addition, we characterized interactions between BAG3 and some of its newly identified partners in greater detail. In particular, bioinformatic analysis revealed that the BAG3 interactome is strongly enriched in proteins functioning within the proteasome-ubiquitination process and that compose the proteasome complex itself, suggesting that a critical biological function of BAG3 is associated with the proteasome. Functional studies demonstrated that BAG3 indeed interacts with the proteasome and modulates its activity, sustaining cell survival and underlying resistance to therapy through the down-modulation of apoptosis. Taken as a whole, this study expands our knowledge of the BAG3 interactome, provides a valuable resource for understanding how BAG3 affects different cellular functions, and demonstrates that biologically relevant data can be harvested using this kind of integrated approach. PMID:23824909

Critical role of Middle East in world petroleum supply and demand

International Nuclear Information System (INIS)

Riva, J.P., Jr.

1992-01-01

The location, production, and transportation of oil consumed in the world each day is of vital importance to good international relationships. Since most of the remaining world's oil reserves are located in the Persian Gulf, the region's critical role in the future is accordingly over-emphasized

Revealing the Relationship between Reading Interest and Critical Thinking Skills through Remap GI and Remap Jigsaw

Science.gov (United States)

Zubaidah, Siti; Corebima, Aloysius Duran; Mahanal, Susriyati; Mistianah

2018-01-01

The aim of this research was to reveal the relationship between student's reading interest and critical thinking skills through Reading Concept Map Group Investigation (Remap GI) and Reading Concept Map Jigsaw (Remap Jigsaw) learning models. To do so, two science classes from first grade of two Senior High Schools in Malang, Indonesia were…

Role of Personality Traits, Learning Styles and Metacognition in Predicting Critical Thinking of Undergraduate Students

Directory of Open Access Journals (Sweden)

Soliemanifar O

2015-04-01

The aim of this study was to investigate the role of personality traits, learning styles and metacognition in predicting critical thinking. Instrument & Methods: In this descriptive correlative study, 240 students (130 girls and 110 boys of Ahvaz Shahid Chamran University were selected by multi-stage random sampling method. The instruments for collecting data were NEO Five-Factor Inventory, learning style inventory of Kolb (LSI, metacognitive assessment inventory (MAI of Schraw & Dennison (1994 and California Critical Thinking Skills Test (CCTST. The data were analyzed using Pearson correlation coefficient, stepwise regression analysis and Canonical correlation analysis.  Findings: Openness to experiment (b=0.41, conscientiousness (b=0.28, abstract conceptualization (b=0.39, active experimentation (b=0.22, reflective observation (b=0.12, knowledge of cognition (b=0.47 and regulation of cognition (b=0.29 were effective in predicting critical thinking. Openness to experiment and conscientiousness (r2=0.25, active experimentation, abstract conceptualization and reflective observation learning styles (r2=0.21 and knowledge and regulation of cognition metacognitions (r2=0.3 had an important role in explaining critical thinking. The linear combination of critical thinking skills (evaluation, analysis, inference was predictable by a linear combination of dispositional-cognitive factors (openness, conscientiousness, abstract conceptualization, active experimentation, knowledge of cognition and regulation of cognition. Conclusion: Personality traits, learning styles and metacognition, as dispositional-cognitive factors, play a significant role in students' critical thinking.

Exploring the Critical Role of Motivation to Transfer in the Training Transfer Process

Science.gov (United States)

Grohmann, Anna; Beller, Johannes; Kauffeld, Simone

2014-01-01

The present study aims at exploring the critical role of motivation to transfer within the training transfer process. In a sample of N?=?252 employees of one industrial company, one peer rating and several self-ratings of transfer were used to investigate the mediating role of motivation to transfer in the relationship between training…

Criticism in izibongo zamakhosi : The changing role of the modern ...

African Journals Online (AJOL)

The imbongi was free in the times of the really powerful Zulu kings to pass any criticism he saw fit within the ambit of the king's praises, in order to alert the king to his peoples' opinions as well as caution him on certain actions. Today the role of the imbongi is far more tenuous. In times gone by, this man not only played a ...

Crystal Structure of Acivicin-Inhibited [gamma]-Glutamyltranspeptidase Reveals Critical Roles for Its C-Terminus in Autoprocessing and Catalysis

Energy Technology Data Exchange (ETDEWEB)

Williams, Kristin; Cullati, Sierra; Sand, Aaron; Biterova, Ekaterina I.; Barycki, Joseph J.; (UNL)

2009-03-27

Helicobacter pylori {gamma}-glutamyltranspeptidase (HpGT) is a general {gamma}-glutamyl hydrolase and a demonstrated virulence factor. The enzyme confers a growth advantage to the bacterium, providing essential amino acid precursors by initiating the degradation of extracellular glutathione and glutamine. HpGT is a member of the N-terminal nucleophile (Ntn) hydrolase superfamily and undergoes autoprocessing to generate the active form of the enzyme. Acivicin is a widely used {gamma}-glutamyltranspeptidase inhibitor that covalently modifies the enzyme, but its precise mechanism of action remains unclear. The time-dependent inactivation of HpGT exhibits a hyperbolic dependence on acivicin concentration with k{sub max} = 0.033 {+-} 0.006 s{sup -1} and K{sub I} = 19.7 {+-} 7.2 {micro}M. Structure determination of acivicin-modified HpGT (1.7 {angstrom}; R{sub factor} = 17.9%; R{sub free} = 20.8%) demonstrates that acivicin is accommodated within the {gamma}-glutamyl binding pocket of the enzyme. The hydroxyl group of Thr 380, the catalytic nucleophile in the autoprocessing and enzymatic reactions, displaces chloride from the acivicin ring to form the covalently linked complex. Within the acivicin-modified HpGT structure, the C-terminus of the protein becomes ordered with Phe 567 positioned over the active site. Substitution or deletion of Phe 567 leads to a >10-fold reduction in enzymatic activity, underscoring its importance in catalysis. The mobile C-terminus is positioned by several electrostatic interactions within the C-terminal region, most notably a salt bridge between Arg 475 and Glu 566. Mutational analysis reveals that Arg 475 is critical for the proper placement of the C-terminal region, the Tyr 433 containing loop, and the proposed oxyanion hole.

Role of Email in Intercultural Communication of Criticism in a Chinese English Curriculum Reform Context

Science.gov (United States)

Lü, Linqiong

2018-01-01

Western teachers working in China often experience cultural conflicts arising from, for instance, the ways that Chinese students perceive face and express criticism. To better understand these face-concerned conflicts, this paper explores the role and significance of email for a group of Chinese students to communicate pedagogical criticism with…

ROLE, INTERESTS AND CRITICS OF CREDIT RATING AGENCIES

Directory of Open Access Journals (Sweden)

Suzana Baresa

2012-06-01

Full Text Available Key role of credit rating agencies is reducing the asymmetry information about credit quality (of governments, business entities or securities between issuers and investors, and ensuring a common standard of measuring the creditworthiness. Credit rating agencies are engaged in the sale of opinions about creditworthiness in the form of an alphabetical letter or symbol, which represents a unique ranking. Their opinion is not a guarantee, but it largely dictates the costs and the profits in the financial markets. This work shows the influence of credit rating agencies to investors and publishers, and their role as market regulators. Conflict of interest is a fundamental problem, which is caused by their way of doing business, it arises from their two main objectives: profit and market regulation, which will be explored in the work. Looking back in history credit rating agencies often selected goal of making a profit at the cost of market regulation, therefore they have caused the collapse of the market, and founded themselves criticized by the public.

Ecological roles of dominant and rare prokaryotes in acid mine drainage revealed by metagenomics and metatranscriptomics.

Science.gov (United States)

Hua, Zheng-Shuang; Han, Yu-Jiao; Chen, Lin-Xing; Liu, Jun; Hu, Min; Li, Sheng-Jin; Kuang, Jia-Liang; Chain, Patrick S G; Huang, Li-Nan; Shu, Wen-Sheng

2015-06-01

High-throughput sequencing is expanding our knowledge of microbial diversity in the environment. Still, understanding the metabolic potentials and ecological roles of rare and uncultured microbes in natural communities remains a major challenge. To this end, we applied a 'divide and conquer' strategy that partitioned a massive metagenomic data set (>100 Gbp) into subsets based on K-mer frequency in sequence assembly to a low-diversity acid mine drainage (AMD) microbial community and, by integrating with an additional metatranscriptomic assembly, successfully obtained 11 draft genomes most of which represent yet uncultured and/or rare taxa (relative abundance 90%) and its metabolic potentials and gene expression profile, providing initial molecular insights into the ecological role of these lesser known, but potentially important, microorganisms in the AMD environment. Gene transcriptional analysis of the active taxa revealed major metabolic capabilities executed in situ, including carbon- and nitrogen-related metabolisms associated with syntrophic interactions, iron and sulfur oxidation, which are key in energy conservation and AMD generation, and the mechanisms of adaptation and response to the environmental stresses (heavy metals, low pH and oxidative stress). Remarkably, nitrogen fixation and sulfur oxidation were performed by the rare taxa, indicating their critical roles in the overall functioning and assembly of the AMD community. Our study demonstrates the potential of the 'divide and conquer' strategy in high-throughput sequencing data assembly for genome reconstruction and functional partitioning analysis of both dominant and rare species in natural microbial assemblages.

Professional autonomy and job satisfaction: survey of critical care nurses in mainland Greece.

Science.gov (United States)

Iliopoulou, Katerina K; While, Alison E

2010-11-01

This paper is a report of a study conducted to describe Greek critical care nurses' views on professional autonomy and its relationship with job satisfaction and other work-related variables. Professional autonomy is generally considered a highly desirable nursing attribute and a major factor in nurse job satisfaction. In the critical care environment, a high level of accountability, responsibility and autonomy are required to optimize outcomes of critically unstable patients. A questionnaire survey was conducted with a convenience sample of Greek critical care nurses (n = 431; response rate 70%) in 2007. Data were collected on professional autonomy, job satisfaction, role conflict and role ambiguity. Overall, nurses reported acting moderately autonomously. Younger nurses reported statistically significant lower levels of autonomy. Higher levels of autonomy were reported by female nurses. Multiple logistic regression revealed that appointment level, type of critical care unit and registration with a professional organization were independently associated with autonomy. A positive moderate association was found between reported autonomy, job satisfaction, role conflict and role ambiguity, but there was no relationship between job satisfaction and reported role conflict and role ambiguity. Further education, role enhancement and support are required for nurses working in critical care in Greece if they are to achieve the maximum potential of their professional role. Failure to address the perceptions of professional autonomy may have an impact on staff retention, because of job dissatisfaction. © 2010 Blackwell Publishing Ltd.

Changing the Culture of Academic Medicine: Critical Mass or Critical Actors?

Science.gov (United States)

Helitzer, Deborah L; Newbill, Sharon L; Cardinali, Gina; Morahan, Page S; Chang, Shine; Magrane, Diane

2017-05-01

By 2006, women constituted 34% of academic medical faculty, reaching a critical mass. Theoretically, with critical mass, culture and policy supportive of gender equity should be evident. We explore whether having a critical mass of women transforms institutional culture and organizational change. Career development program participants were interviewed to elucidate their experiences in academic health centers (AHCs). Focus group discussions were held with institutional leaders to explore their perceptions about contemporary challenges related to gender and leadership. Content analysis of both data sources revealed points of convergence. Findings were interpreted using the theory of critical mass. Two nested domains emerged: the individual domain included the rewards and personal satisfaction of meaningful work, personal agency, tensions between cultural expectations of family and academic roles, and women's efforts to work for gender equity. The institutional domain depicted the sociocultural environment of AHCs that shaped women's experience, both personally and professionally, lack of institutional strategies to engage women in organizational initiatives, and the influence of one leader on women's ascent to leadership. The predominant evidence from this research demonstrates that the institutional barriers and sociocultural environment continue to be formidable obstacles confronting women, stalling the transformational effects expected from achieving a critical mass of women faculty. We conclude that the promise of critical mass as a turning point for women should be abandoned in favor of "critical actor" leaders, both women and men, who individually and collectively have the commitment and power to create gender-equitable cultures in AHCs.

Structural Snapshots of an Engineered Cystathionine-γ-lyase Reveal the Critical Role of Electrostatic Interactions in the Active Site

Energy Technology Data Exchange (ETDEWEB)

Yan, Wupeng; Stone, Everett; Zhang, Yan Jessie

2017-02-01

Enzyme therapeutics that can degrade l-methionine (l-Met) are of great interest as numerous malignancies are exquisitely sensitive to l-Met depletion. To exhaust the pool of methionine in human serum, we previously engineered an l-Met-degrading enzyme based on the human cystathionine-γ-lyase scaffold (hCGL-NLV) to circumvent immunogenicity and stability issues observed in the preclinical application of bacterially derived methionine-γ-lyases. To gain further insights into the structure–activity relationships governing the chemistry of the hCGL-NLV lead molecule, we undertook a biophysical characterization campaign that captured crystal structures (2.2 Å) of hCGL-NLV with distinct reaction intermediates, including internal aldimine, substrate-bound, gem-diamine, and external aldimine forms. Curiously, an alternate form of hCGL-NLV that crystallized under higher-salt conditions revealed a locally unfolded active site, correlating with inhibition of activity as a function of ionic strength. Subsequent mutational and kinetic experiments pinpointed that a salt bridge between the phosphate of the essential cofactor pyridoxal 5'-phosphate (PLP) and residue R62 plays an important role in catalyzing β- and γ-eliminations. Our study suggests that solvent ions such as NaCl disrupt electrostatic interactions between R62 and PLP, decreasing catalytic efficiency.

Controlling superconductivity by tunable quantum critical points.

Science.gov (United States)

Seo, S; Park, E; Bauer, E D; Ronning, F; Kim, J N; Shim, J-H; Thompson, J D; Park, Tuson

2015-03-04

The heavy fermion compound CeRhIn5 is a rare example where a quantum critical point, hidden by a dome of superconductivity, has been explicitly revealed and found to have a local nature. The lack of additional examples of local types of quantum critical points associated with superconductivity, however, has made it difficult to unravel the role of quantum fluctuations in forming Cooper pairs. Here, we show the precise control of superconductivity by tunable quantum critical points in CeRhIn5. Slight tin-substitution for indium in CeRhIn5 shifts its antiferromagnetic quantum critical point from 2.3 GPa to 1.3 GPa and induces a residual impurity scattering 300 times larger than that of pure CeRhIn5, which should be sufficient to preclude superconductivity. Nevertheless, superconductivity occurs at the quantum critical point of the tin-doped metal. These results underline that fluctuations from the antiferromagnetic quantum criticality promote unconventional superconductivity in CeRhIn5.

Bioinformatics analysis of RNA-seq data revealed critical genes in colon adenocarcinoma.

Science.gov (United States)

Xi, W-D; Liu, Y-J; Sun, X-B; Shan, J; Yi, L; Zhang, T-T

2017-07-01

RNA-seq data of colon adenocarcinoma (COAD) were analyzed with bioinformatics tools to discover critical genes in the disease. Relevant small molecule drugs, transcription factors (TFs) and microRNAs (miRNAs) were also investigated. RNA-seq data of COAD were downloaded from The Cancer Genome Atlas (TCGA). Differential analysis was performed with package edgeR. False positive discovery (FDR) 1 were set as the cut-offs to screen out differentially expressed genes (DEGs). Gene coexpression network was constructed with package Ebcoexpress. GO enrichment analysis was performed for the DEGs in the gene coexpression network with DAVID. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was also performed for the genes with KOBASS 2.0. Modules were identified with MCODE of Cytoscape. Relevant small molecules drugs were predicted by Connectivity map. Relevant miRNAs and TFs were searched by WebGestalt. A total of 457 DEGs, including 255 up-regulated and 202 down-regulated genes, were identified from 437 COAD and 39 control samples. A gene coexpression network was constructed containing 40 DEGs and 101 edges. The genes were mainly associated with collagen fibril organization, extracellular matrix organization and translation. Two modules were identified from the gene coexpression network, which were implicated in muscle contraction and extracellular matrix organization, respectively. Several critical genes were disclosed, such as MYH11, COL5A2 and ribosomal proteins. Nine relevant small molecule drugs were identified, such as scriptaid and STOCK1N-35874. Accordingly, a total of 17 TFs and 10 miRNAs related to COAD were acquired, such as ETS2, NFAT, AP4, miR-124A, MiR-9, miR-96 and let-7. Several critical genes and relevant drugs, TFs and miRNAs were revealed in COAD. These findings could advance the understanding of the disease and benefit therapy development.

A critical role for noncoding 5S rRNA in regulating Mdmx stability.

Science.gov (United States)

Li, Muyang; Gu, Wei

2011-09-16

Both p53 and Mdmx are ubiquitinated and degraded by the same E3 ligase Mdm2; interestingly, however, while p53 is rapidly degraded by Mdm2, Mdmx is a stable protein in most cancer cells. Thus, the mechanism by which Mdmx is degraded by Mdm2 needs further elucidation. Here, we identified the noncoding 5S rRNA as a major component of Mdmx-associated complexes from human cells. We show that 5S rRNA acts as a natural inhibitor of Mdmx degradation by Mdm2. RNAi-mediated knockdown of endogenous 5S rRNA, while not affecting p53 levels, significantly induces Mdmx degradation and, subsequently, activates p53-dependent growth arrest. Notably, 5S rRNA binds the RING domain of Mdmx and blocks its ubiquitination by Mdm2, whereas Mdm2-mediated p53 ubiquitination remains intact. These results provide insights into the differential effects on p53 and Mdmx by Mdm2 in vivo and reveal a critical role for noncoding 5S rRNA in modulating the p53-Mdmx axis. Copyright © 2011 Elsevier Inc. All rights reserved.

Critical role of bicarbonate and bicarbonate transporters in cardiac function

OpenAIRE

Wang, Hong-Sheng; Chen, Yamei; Vairamani, Kanimozhi; Shull, Gary E

2014-01-01

Bicarbonate is one of the major anions in mammalian tissues and extracellular fluids. Along with accompanying H+, HCO3- is generated from CO2 and H2O, either spontaneously or via the catalytic activity of carbonic anhydrase. It serves as a component of the major buffer system, thereby playing a critical role in pH homeostasis. Bicarbonate can also be utilized by a variety of ion transporters, often working in coupled systems, to transport other ions and organic substrates across cell membrane...

The importance of service-users' perspectives: A systematic review of qualitative evidence reveals overlooked critical features of weight management programmes.

Science.gov (United States)

Sutcliffe, Katy; Melendez-Torres, G J; Burchett, Helen E D; Richardson, Michelle; Rees, Rebecca; Thomas, James

2018-03-14

Extensive research effort shows that weight management programmes (WMPs) targeting both diet and exercise are broadly effective. However, the critical features of WMPs remain unclear. To develop a deeper understanding of WMPs critical features, we undertook a systematic review of qualitative evidence. We sought to understand from a service-user perspective how programmes are experienced, and may be effective, on the ground. We identified qualitative studies from existing reviews and updated the searches of one review. We included UK studies capturing the views of adult WMP users. Thematic analysis was used inductively to code and synthesize the evidence. Service users were emphatic that supportive relationships, with service providers or WMP peers, are the most critical aspect of WMPs. Supportive relationships were described as providing an extrinsic motivator or "hook" which helped to overcome barriers such as scepticism about dietary advice or a lack confidence to engage in physical activity. The evidence revealed that service-users' understandings of the critical features of WMPs differ from the focus of health promotion guidance or descriptions of evaluated programmes which largely emphasize educational or goal setting aspects of WMPs. Existing programme guidance may not therefore fully address the needs of service users. The study illustrates that the perspectives of service users can reveal unanticipated intervention mechanisms or underemphasized critical features and underscores the value of a holistic understanding about "what happens" in complex psychosocial interventions such as WMPs. © 2017 The Authors Health Expectations published by John Wiley & Sons Ltd.

Slc39a7/zip7 plays a critical role in development and zinc homeostasis in zebrafish.

Directory of Open Access Journals (Sweden)

Guang Yan

Full Text Available BACKGROUND: Slc39a7/Zip7, also known as Ke4, is a member of solute carrier family 39 (Slc39a and plays a critical role in regulating cell growth and death. Because the function of Zip7 in vivo was unclear, the present study investigated the function of zip7 in vertebrate development and zinc metabolism using zebrafish as a model organism. PRINCIPAL FINDING: Using real-time PCR to determine the gene expression pattern of zip7 during zebrafish development, we found that zip7 mRNA is expressed throughout embryonic development and into maturity. Interestingly, whole mount in situ hybridization revealed that while zip7 mRNA is ubiquitously expressed until 12 hours post-fertilization (hpf; at 24 hpf and beyond, zip7 mRNA was specifically detected only in eyes. Morpholino-antisense (MO gene knockdown assay revealed that downregulation of zip7 expression resulted in several morphological defects in zebrafish including decreased head size, smaller eyes, shorter palates, and shorter and curved spinal cords. Analysis by synchrotron radiation X-ray fluorescence (SR-XRF showed reduced concentrations of zinc in brain, eyes, and gills of zip7-MO-injected embryos. Furthermore, incubation of the zip7 knockdown embryos in a zinc-supplemented solution was able to rescue the MO-induced morphological defects. SIGNIFICANCE: Our data suggest that zip7 is required for eye, brain, and skeleton formation during early embryonic development in zebrafish. Moreover, zinc supplementation can partially rescue defects resulting from zip7 gene knockdown. Taken together, our data provide critical insight into a novel function of zip7 in development and zinc homeostasis in vivo in zebrafish.

Mutational analysis of an archaeal minichromosome maintenance protein exterior hairpin reveals critical residues for helicase activity and DNA binding

Directory of Open Access Journals (Sweden)

Brewster Aaron S

2010-08-01

Full Text Available Abstract Background The mini-chromosome maintenance protein (MCM complex is an essential replicative helicase for DNA replication in Archaea and Eukaryotes. While the eukaryotic complex consists of six homologous proteins (MCM2-7, the archaeon Sulfolobus solfataricus has only one MCM protein (ssoMCM, six subunits of which form a homohexamer. We have recently reported a 4.35Å crystal structure of the near full-length ssoMCM. The structure reveals a total of four β-hairpins per subunit, three of which are located within the main channel or side channels of the ssoMCM hexamer model generated based on the symmetry of the N-terminal Methanothermobacter thermautotrophicus (mtMCM structure. The fourth β-hairpin, however, is located on the exterior of the hexamer, near the exit of the putative side channels and next to the ATP binding pocket. Results In order to better understand this hairpin's role in DNA binding and helicase activity, we performed a detailed mutational and biochemical analysis of nine residues on this exterior β-hairpin (EXT-hp. We examined the activities of the mutants related to their helicase function, including hexamerization, ATPase, DNA binding and helicase activities. The assays showed that some of the residues on this EXT-hp play a role for DNA binding as well as for helicase activity. Conclusions These results implicate several current theories regarding helicase activity by this critical hexameric enzyme. As the data suggest that EXT-hp is involved in DNA binding, the results reported here imply that the EXT-hp located near the exterior exit of the side channels may play a role in contacting DNA substrate in a manner that affects DNA unwinding.

Changing the Culture of Academic Medicine: Critical Mass or Critical Actors?

Science.gov (United States)

Newbill, Sharon L.; Cardinali, Gina; Morahan, Page S.; Chang, Shine; Magrane, Diane

2017-01-01

Abstract Purpose: By 2006, women constituted 34% of academic medical faculty, reaching a critical mass. Theoretically, with critical mass, culture and policy supportive of gender equity should be evident. We explore whether having a critical mass of women transforms institutional culture and organizational change. Methods: Career development program participants were interviewed to elucidate their experiences in academic health centers (AHCs). Focus group discussions were held with institutional leaders to explore their perceptions about contemporary challenges related to gender and leadership. Content analysis of both data sources revealed points of convergence. Findings were interpreted using the theory of critical mass. Results: Two nested domains emerged: the individual domain included the rewards and personal satisfaction of meaningful work, personal agency, tensions between cultural expectations of family and academic roles, and women's efforts to work for gender equity. The institutional domain depicted the sociocultural environment of AHCs that shaped women's experience, both personally and professionally, lack of institutional strategies to engage women in organizational initiatives, and the influence of one leader on women's ascent to leadership. Conclusions: The predominant evidence from this research demonstrates that the institutional barriers and sociocultural environment continue to be formidable obstacles confronting women, stalling the transformational effects expected from achieving a critical mass of women faculty. We conclude that the promise of critical mass as a turning point for women should be abandoned in favor of “critical actor” leaders, both women and men, who individually and collectively have the commitment and power to create gender-equitable cultures in AHCs. PMID:28092473

Nurse educators' critical thinking: A mixed methods exploration.

Science.gov (United States)

Raymond, Christy; Profetto-McGrath, Joanne; Myrick, Florence; Strean, William B

2018-07-01

Nurse educator's critical thinking remains unexamined as a key factor in the development of students' critical thinking. The objective of this study is to understand how nurse educators reveal their critical thinking in the clinical setting while supervising students. This study uses a single-phase triangulation mixed methods design with multiple data gathering techniques. Participants for this study are clinical nurse educators from a large Western Canadian baccalaureate nursing program who teach 2nd or 3rd year students in medical-surgical settings. Participants for this study completed a demographic survey, the California Critical Thinking Skills Test (CCTST), the California Critical Thinking Disposition Inventory (CCTDI), participant observation in a clinical practice setting, and semi-structured interviews. The results from the California Critical Thinking assessments (CCTST and CCTDI) show that participants are positively inclined and have a moderate to strong ability to think critically, similar to other studies. Participants find it difficult to describe how they reveal their critical thinking in the clinical setting, yet all participants use role modeling and questioning to share their critical thinking with students. When the quantitative and qualitative results are compared, it is apparent that the confidence in reasoning subscale of the California Critical Thinking Skills Test is higher in those educators who more frequently demonstrate and voice engagement in reflective activities. Dispositions associated with critical thinking, as measured by the California Critical Thinking Disposition Inventory, are more easily observed compared to critical thinking skills. This study is a beginning exploration of nurse educators' critical thinking-in-action. Our mixed methods approach uncovers a valuable approach to understanding the complexity of nurse educators' critical thinking. Further study is needed to uncover how nurse educators' can specifically enact

REVEAL - A tool for rule driven analysis of safety critical software

International Nuclear Information System (INIS)

Miedl, H.; Kersken, M.

1998-01-01

As the determination of ultrahigh reliability figures for safety critical software is hardly possible, national and international guidelines and standards give mainly requirements for the qualitative evaluation of software. An analysis whether all these requirements are fulfilled is time and effort consuming and prone to errors, if performed manually by analysts, and should instead be dedicated to tools as far as possible. There are many ''general-purpose'' software analysis tools, both static and dynamic, which help analyzing the source code. However, they are not designed to assess the adherence to specific requirements of guidelines and standards in the nuclear field. Against the background of the development of I and C systems in the nuclear field which are based on digital techniques and implemented in high level language, it is essential that the assessor or licenser has a tool with which he can automatically and uniformly qualify as many aspects as possible of the high level language software. For this purpose the software analysis tool REVEAL has been developed at ISTec and the Halden Reactor Project. (author)

Critical role of NKT cells in posttransplant alloantibody production.

Science.gov (United States)

Zimmerer, J M; Swamy, P; Sanghavi, P B; Wright, C L; Abdel-Rasoul, M; Elzein, S M; Brutkiewicz, R R; Bumgardner, G L

2014-11-01

We previously reported that posttransplant alloantibody production in CD8-deficient hosts is IL-4+ CD4+ T cell-dependent and IgG1 isotype-dominant. The current studies investigated the hypothesis that IL-4-producing natural killer T cells (NKT cells) contribute to maximal alloantibody production. To investigate this, alloantibody levels were examined in CD8-deficient WT, CD1d KO and Jα18 KO transplant recipients. We found that the magnitude of IgG1 alloantibody production was critically dependent on the presence of type I NKT cells, which are activated by day 1 posttransplant. Unexpectedly, type I NKT cell contribution to enhanced IgG1 alloantibody levels was interferon-γ-dependent and IL-4-independent. Cognate interactions between type I NKT and B cells alone do not stimulate alloantibody production. Instead, NKT cells appear to enhance maturation of IL-4+ CD4+ T cells. To our knowledge, this is the first report to substantiate a critical role for type I NKT cells in enhancing in vivo antibody production in response to endogenous antigenic stimuli. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

X-ray fluorescence microscopy reveals the role of selenium in spermatogenesis

Science.gov (United States)

Kehr, Sebastian; Malinouski, Mikalai; Finney, Lydia; Vogt, Stefan; Labunskyy, Vyacheslav M.; Kasaikina, Marina V.; Carlson, Bradley A.; Zhou, You; Hatfield, Dolph L.; Gladyshev, Vadim N.

2009-01-01

Selenium (Se) is a trace element with important roles in human health. Several selenoproteins have essential functions in development. However, the cellular and tissue distribution of Se remains largely unknown because of the lack of analytical techniques that image this element with sufficient sensitivity and resolution. Herein, we report that X-ray fluorescence microscopy (XFM) can be used to visualize and quantify the tissue, cellular and subcellular topography of Se. We applied this technique to characterize the role of Se in spermatogenesis and identified a dramatic Se enrichment specifically in late spermatids, a pattern that was not seen in any other elemental maps. This enrichment was due to elevated levels of the mitochondrial form of glutathione peroxidase 4 and was fully dependent on the supplies of Se by Selenoprotein P. High-resolution scans revealed that Se concentrated near the lumen side of elongating spermatids, where structural components of sperm are formed. During spermatogenesis, maximal Se associated with decreased phosphorus, whereas Zn did not change. In sperm, Se was primarily in the midpiece and co-localized with Cu and Fe. XFM allowed quantification of Se in the midpiece (0.8 fg) and head (0.14 fg) of individual sperm cells, revealing the ability of sperm cells to handle the amounts of this element well above its toxic levels. Overall, the use of XFM allowed visualization of tissue and cellular Se and provided important insights in the role of this and other trace elements in spermatogenesis. PMID:19379757

Childhood Maltreatment, Depressive Symptoms, and Body Dissatisfaction in Patients with Binge Eating Disorder: The Mediating Role of Self-Criticism

Science.gov (United States)

Dunkley, David M.; Masheb, Robin M.; Grilo, Carlos M.

2010-01-01

Objective We examined the mediating role of self-criticism in the relation between childhood maltreatment and both depressive symptoms and body dissatisfaction in patients with binge eating disorder (BED). Method Participants were 170 BED patients who completed measures of childhood maltreatment, self-criticism, self-esteem, depressive symptoms, and body dissatisfaction. Results Specific forms of childhood maltreatment (emotional abuse, sexual abuse) were significantly associated with body dissatisfaction. Path analyses demonstrated that self-criticism fully mediated the relation between emotional abuse and both depressive symptoms and body dissatisfaction. Specificity for the mediating role of self-criticism was demonstrated in comparison to other potential mediators (low self-esteem) and alternative competing mediation models. Conclusion These results highlight self-criticism as a potential mechanism through which certain forms of childhood maltreatment may be associated with depressive symptoms and body dissatisfaction in BED patients. PMID:20119938

The Critical Role of Stewardship in Fund Raising: The Coaches vs. Cancer Campaign.

Science.gov (United States)

Worley, Debra A.; Little, Jennifer K.

2002-01-01

Examines the critical role of stewardship in the process of fund raising. Uses the Coaches vs. Cancer campaign to illustrate the limitations of the public relations ROPE (research, objectives, planning, and evaluation) model in explaining fund raising success, and supports K.S. Kelly's contention that addition of a fifth step to the model, the…

ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

International Nuclear Information System (INIS)

Doi, Keiko; Fujimoto, Takahiro; Okamura, Tadashi; Ogawa, Masahiro; Tanaka, Yoko; Mototani, Yasumasa; Goto, Motohito; Ota, Takeharu; Matsuzaki, Hiroshi; Kuroki, Masahide; Tsunoda, Toshiyuki; Sasazuki, Takehiko; Shirasawa, Senji

2012-01-01

Highlights: ► We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. ► Zfat-deficiency leads to reduction in the number of the peripheral T cells. ► Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. ► Decreased expression of IL-7Rα, IL-2Rα and IL-2 in Zfat-deficient peripheral T cells. ► Zfat plays critical roles in peripheral T cell homeostasis. -- Abstract: ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in the immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7Rα and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2Rα expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.

Reconstitution of active human core Mediator complex reveals a critical role of the MED14 subunit.

Science.gov (United States)

Cevher, Murat A; Shi, Yi; Li, Dan; Chait, Brian T; Malik, Sohail; Roeder, Robert G

2014-12-01

The evolutionarily conserved Mediator complex is a critical coactivator for RNA polymerase II (Pol II)-mediated transcription. Here we report the reconstitution of a functional 15-subunit human core Mediator complex and its characterization by functional assays and chemical cross-linking coupled to MS (CX-MS). Whereas the reconstituted head and middle modules can stably associate, basal and coactivator functions are acquired only after incorporation of MED14 into the bimodular complex. This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. Altogether, our analyses identify MED14 as both an architectural and a functional backbone of the Mediator complex. We further establish a conditional requirement for metazoan-specific MED26 that becomes evident in the presence of heterologous nuclear factors. This general approach paves the way for systematic dissection of the multiple layers of functionality associated with the Mediator complex.

Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis.

Science.gov (United States)

Saroha, Ashish; Pewzner-Jung, Yael; Ferreira, Natalia S; Sharma, Piyush; Jouan, Youenn; Kelly, Samuel L; Feldmesser, Ester; Merrill, Alfred H; Trottein, François; Paget, Christophe; Lang, Karl S; Futerman, Anthony H

2017-01-01

The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here, we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T ( i NKT) cell maturation in the thymus and homeostasis in the liver. Ceramide synthase 2-null mice, which lack VLC-SLs, were susceptible to a hepatotropic strain of lymphocytic choriomeningitis virus, which is due to a reduction in the number of i NKT cells. Bone marrow chimera experiments indicated that hematopoietic-derived VLC-SLs are essential for maturation of i NKT cells in the thymus, whereas parenchymal-derived VLC-SLs are crucial for i NKT cell survival and maintenance in the liver. Our findings suggest a critical role for VLC-SL in i NKT cell physiology.

Can We Protect the Gut in Critical Illness: The Role of Growth Factors and Other Novel Approaches

Science.gov (United States)

Dominguez, Jessica A.; Coopersmith, Craig M.

2010-01-01

Synopsis The intestine plays a central role in the pathophysiology of critical illness and is frequently called the “motor” of the systemic inflammatory response. Perturbations to the intestinal barrier can lead to distant organ damage and multiple organ failure. Therefore, identifying ways to preserve intestinal integrity may be of paramount importance. Growth factors and other peptides have emerged as potential tools for modulation of intestinal inflammation and repair due to their roles in cellular proliferation, differentiation, migration, and survival. In this review, we will examine the involvement of growth factors and other peptides in intestinal epithelial repair during critical illness and their potential use as therapeutic targets. PMID:20643306

Can we protect the gut in critical illness? The role of growth factors and other novel approaches.

Science.gov (United States)

Dominguez, Jessica A; Coopersmith, Craig M

2010-07-01

The intestine plays a central role in the pathophysiology of critical illness and is frequently called the "motor" of the systemic inflammatory response. Perturbations to the intestinal barrier can lead to distant organ damage and multiple organ failure. Therefore, identifying ways to preserve intestinal integrity may be of paramount importance. Growth factors and other peptides have emerged as potential tools for modulation of intestinal inflammation and repair due to their roles in cellular proliferation, differentiation, migration, and survival. This review examines the involvement of growth factors and other peptides in intestinal epithelial repair during critical illness and their potential use as therapeutic targets. Copyright 2010 Elsevier Inc. All rights reserved.

Critical role of tumor necrosis factor receptor 1 in the pathogenesis of pulmonary emphysema in mice.

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Fujita, Masaki; Ouchi, Hiroshi; Ikegame, Satoshi; Harada, Eiji; Matsumoto, Takemasa; Uchino, Junji; Nakanishi, Yoichi; Watanabe, Kentaro

2016-01-01

COPD is a major cause of chronic morbidity and mortality throughout the world. Although tumor necrosis factor-α (TNF-α) has a critical role in the development of COPD, the role of different TNF receptors (TNFRs) in pulmonary emphysema has not been resolved. We aimed to clarify the role of TNFRs in the development of pulmonary emphysema. TNF-α transgenic mice, a murine model of COPD in which the mice spontaneously develop emphysema with a large increase in lung volume and pulmonary hypertension, were crossed with either TNFR1-deficient mice or TNFR2-deficient mice. After 6 months, the gross appearance of the lung, lung histology, and pulmonary and cardiac physiology were determined. In addition, the relationship between apoptosis and emphysema was investigated. Pulmonary emphysema-like changes disappeared with deletion of TNFR1. However, slight improvements were attained with deletion of TNFR2. Apoptotic cells in the interstitium of the lung were observed in TNF-α transgenic mice. The apoptotic signals through TNFR1 appear critical for the pathogenesis of pulmonary emphysema. In contrast, the inflammatory process has a less important role for the development of emphysema.

'Not good enough:' Exploring self-criticism's role as a mediator between childhood emotional abuse & adult binge eating.

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Feinson, Marjorie C; Hornik-Lurie, Tzipi

2016-12-01

Empirical studies have identified emotional abuse in childhood (CEA) as a risk factor with long-term implications for psychological problems. Indeed, recent studies indicate it is more prevalent than behavioral forms of abuse, (i.e. childhood sexual and physical abuse) and the childhood trauma most clearly associated with subsequent eating pathology in adulthood. However, relatively little is understood about the mechanisms linking these distal experiences. This study explores three psychological mechanisms - self-criticism (SC), depression and anxiety symptoms - as plausible mediators that may account for the relationship between CEA and binge eating (BE) among adult women. Detailed telephone interviews conducted with a community-based sample of 498 adult women (mean age 44) assess BE, CEA and SC along with the most frequently researched psychological variables, anxiety and depression. Regression analyses reveal that BE is partially explained by CEA along with the three mediators. Bootstrapping analysis, which compares multiple mediators within a single model using thousands of repeated random sampling observations from the data set, reveals a striking finding: SC is the only psychological variable that makes a significant contribution to explaining BE severity. The unique role of punitive self-evaluations vis-à-vis binge eating warrants additional research and, in the interim, that clinicians consider broadening treatment interventions accordingly. Copyright © 2016. Published by Elsevier Ltd.

Role of Serum Iron in the Activation of Lipid Peroxidation in Critical Conditions

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Yu. P. Orlov

2006-01-01

Full Text Available Twenty-four critically ill patients due to generalized purulent peritonitis, pancreatonecrosis, thermal skin injuries, and severe poisoning by acetic acid were examined. The general regularities of the effect of high serum iron concentrations on the health status of patients, on the activity of antioxidative enzymes, and on the initiation of lipid peroxidation (LPO processes, as supported by the values of Fe2+-induced chemiluminescence, were revealed. In critically ill patients, iron metabolism occurs with the overload of a transport protein, such as transferrin, which is caused by intravascular hemolysis and hemoglobin metabolism to ionized iron. The overload of proteins responsible for iron transport leads to the tissue accumulation of free (ferrous and ferric iron that is actively involved in the processes of LPO initiation with excess synthesis of cytotoxic radicals, which in turn accounts for the severity of endotoxicosis.

The imidazopyridine derivative JK184 reveals dual roles for microtubules in Hedgehog signaling.

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Cupido, Tommaso; Rack, Paul G; Firestone, Ari J; Hyman, Joel M; Han, Kyuho; Sinha, Surajit; Ocasio, Cory A; Chen, James K

2009-01-01

Eradicating hedgehogs: The title molecule has been previously identified as a potent inhibitor of the Hedgehog signaling pathway, which gives embryonic cells information needed to develop properly. This molecule is shown to modulate Hedgehog target gene expression by depolymerizing microtubules, thus revealing dual roles of the cytoskeleton in pathway regulation (see figure).

A universal indicator of critical state transitions in noisy complex networked systems.

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Liang, Junhao; Hu, Yanqing; Chen, Guanrong; Zhou, Tianshou

2017-02-23

Critical transition, a phenomenon that a system shifts suddenly from one state to another, occurs in many real-world complex networks. We propose an analytical framework for exactly predicting the critical transition in a complex networked system subjected to noise effects. Our prediction is based on the characteristic return time of a simple one-dimensional system derived from the original higher-dimensional system. This characteristic time, which can be easily calculated using network data, allows us to systematically separate the respective roles of dynamics, noise and topology of the underlying networked system. We find that the noise can either prevent or enhance critical transitions, playing a key role in compensating the network structural defect which suffers from either internal failures or environmental changes, or both. Our analysis of realistic or artificial examples reveals that the characteristic return time is an effective indicator for forecasting the sudden deterioration of complex networks.

ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

Energy Technology Data Exchange (ETDEWEB)

Doi, Keiko [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute of Life Sciences for the Next Generation of Women Scientists, Fukuoka University, Fukuoka (Japan); Fujimoto, Takahiro [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Okamura, Tadashi [Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Ogawa, Masahiro [Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Tanaka, Yoko [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Mototani, Yasumasa; Goto, Motohito [Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Ota, Takeharu; Matsuzaki, Hiroshi [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Kuroki, Masahide [Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Tsunoda, Toshiyuki [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Sasazuki, Takehiko [Institute for Advanced Study, Kyushu University, Fukuoka (Japan); Shirasawa, Senji, E-mail: sshirasa@fukuoka-u.ac.jp [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan)

2012-08-17

Highlights: Black-Right-Pointing-Pointer We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. Black-Right-Pointing-Pointer Zfat-deficiency leads to reduction in the number of the peripheral T cells. Black-Right-Pointing-Pointer Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Decreased expression of IL-7R{alpha}, IL-2R{alpha} and IL-2 in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Zfat plays critical roles in peripheral T cell homeostasis. -- Abstract: ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in the immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7R{alpha} and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2R{alpha} expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.

Cutting edge: A critical functional role for IL-23 in psoriasis.

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Tonel, Giulia; Conrad, Curdin; Laggner, Ute; Di Meglio, Paola; Grys, Katarzyna; McClanahan, Terrill K; Blumenschein, Wendy M; Qin, Jian-Zhong; Xin, Hong; Oldham, Elizabeth; Kastelein, Robert; Nickoloff, Brian J; Nestle, Frank O

2010-11-15

Interleukin-23 is a key cytokine involved in the generation of Th17 effector cells. Clinical efficacy of an anti-p40 mAb blocking both IL-12 and IL-23 and disease association with single nucleotide polymorphisms in the IL23R gene raise the question of a functional role of IL-23 in psoriasis. In this study, we provide a comprehensive analysis of IL-23 and its receptor in psoriasis and demonstrate its functional importance in a disease-relevant model system. The expression of IL-23 and its receptor was increased in the tissues of patients with psoriasis. Injection of a mAb specifically neutralizing human IL-23 showed IL-23-dependent inhibition of psoriasis development comparable to the use of anti-TNF blockers in a clinically relevant xenotransplant mouse model of psoriasis. Together, our results identify a critical functional role for IL-23 in psoriasis and provide the rationale for new treatment strategies in chronic epithelial inflammatory disorders.

The mediating role of self-criticism and dependency in the association between perceptions of maternal caring and depressive symptoms.

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Campos, Rui C; Besser, Avi; Blatt, Sidney J

2010-12-01

This study examined a theoretically based mediation model including participants' perceptions of early relationships with their mother, self-criticism, dependency, and current depressive symptoms. We expect that (a) early relationships characterized by low levels of care and high levels of overprotection will be positively associated with both current depressive state and self-criticism and dependency; (b) high levels of self-criticism and dependency will be positively associated with depressive symptoms; and (c) self-criticism and dependency will play a mediating role in the association between participants' perceptions of early relationships characterized by low levels of care and high levels of overprotection and their current depressive symptoms. A nonclinical community sample of 200 Portuguese adults participated in the study. Perceptions of early relationships were measured using the mother scales of the Parental Bonding Instrument (Parker et al. [1979: Br J Med Psychol 52:1-10]), levels of self-criticism and dependency were measured using the Depressive Experiences Questionnaire (Blatt et al. [1976: J Abn Psy 6:383-389]), and depressive symptoms were measured using the Center for the Epidemiological Studies of Depression Scale (Radloff [1977: Appl Psychol Meas 1:385-401]. Structural equation modeling showed that the link between participants' perceptions of early caretaking relationships with their mothers and their current depressive symptoms is mediated by high levels of self-criticism--a personality trait associated with vulnerability to depression--but not Dependency. However, an ancillary analysis indicated that the link between participants' perceptions of early maternal overprotective relationships and their current depressive symptoms is mediated by high levels of Neediness. Findings underscore the role of perceived early relationships in psychological vulnerability to depression among highly self-critical and among highly needy individuals and

Roles for Drosophila Mushroom Body Neurons in Olfactory Learning and Memory

Science.gov (United States)

Zong, Lin; Tanaka, Nobuaki K.; Ito, Kei; Davis, Ronald L.; Akalal, David-Benjamin G.; Wilson, Curtis F.

2006-01-01

Olfactory learning assays in Drosophila have revealed that distinct brain structures known as mushroom bodies (MBs) are critical for the associative learning and memory of olfactory stimuli. However, the precise roles of the different neurons comprising the MBs are still under debate. The confusion surrounding the roles of the different neurons…

Calreticulin reveals a critical Ca2+ checkpoint in cardiac myofibrillogenesis

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Li, Jian; Pucéat, Michel; Perez-Terzic, Carmen; Mery, Annabelle; Nakamura, Kimitoshi; Michalak, Marek; Krause, Karl-Heinz; Jaconi, Marisa E.

2002-01-01

Calreticulin (crt) is an ubiquitously expressed and multifunctional Ca2+-binding protein that regulates diverse vital cell functions, including Ca2+ storage in the ER and protein folding. Calreticulin deficiency in mice is lethal in utero due to defects in heart development and function. Herein, we used crt − / − embryonic stem (ES) cells differentiated in vitro into cardiac cells to investigate the molecular mechanisms underlying heart failure of knockout embryos. After 8 d of differentiation, beating areas were prominent in ES-derived wild-type (wt) embryoid bodies (EBs), but not in ES-derived crt − / − EBs, despite normal expression levels of cardiac transcription factors. Crt − / − EBs exhibited a severe decrease in expression and a lack of phosphorylation of ventricular myosin light chain 2 (MLC2v), resulting in an impaired organization of myofibrils. Crt − / − phenotype could be recreated in wt cells by chelating extracellular or cytoplasmic Ca2+ with EGTA or BAPTA, or by inhibiting Ca2+/calmodulin-dependent kinases (CaMKs). An imposed ionomycin-triggered cystolic-free Ca2+ concentration ([Ca2+]c) elevation restored the expression, phosphorylation, and insertion of MLC2v into sarcomeric structures and in turn the myofibrillogenesis. The transcription factor myocyte enhancer factor C2 failed to accumulate into nuclei of crt − / − cardiac cells in the absence of ionomycin-triggered [Ca2+]c increase. We conclude that the absence of calreticulin interferes with myofibril formation. Most importantly, calreticulin deficiency revealed the importance of a Ca2+-dependent checkpoint critical for early events during cardiac myofibrillogenesis. PMID:12105184

DMPD: Critical role of toll-like receptors and nucleotide oligomerisation domain inthe regulation of health and disease. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available and nucleotide oligomerisation domain inthe regulation of health and disease. Pu...bmedID 17535871 Title Critical role of toll-like receptors and nucleotide oligomerisation domain inthe regulation of health...17535871 Critical role of toll-like receptors and nucleotide oligomerisation domain inthe regulation of heal...th and disease. Mitchell JA, Paul-Clark MJ, Clarke GW, McMaster SK, Cartwright N. J

A comparison of debate and role play in enhancing critical thinking and communication skills of medical students during problem based learning.

Science.gov (United States)

Latif, Rabia; Mumtaz, Sadaf; Mumtaz, Rafia; Hussain, Aamir

2018-04-18

Debate and role play for learning critical thinking and communication skills are being increasingly used in various undergraduate medical schools worldwide. We aim to compare students' views about effectiveness of two teaching strategies; debate and role play to exercise critical thinking and communication skills during problem-based learning (PBL). This is a comparative, cross-sectional, and questionnaire-based study. Our subjects were second year undergraduate female medical students enrolled in Imam Abdulrahman Bin Faisal University (IAU), College of Medicine from September 2014-2016, divided into 10 small PBL groups (10-13 students/group/year). Students rated role play and debate as equally effective in improving communication skills. Debate was rated superior to role play in "opening new avenues of thinking" (p-value is 0.01), whereas in "integration of knowledge of basic medical sciences with clinical skills" and "reflection of real life experience" students rated role play being superior to debate (p-value 0.01 and 0.00, respectively). Both role play and debate are well accepted by the students in PBL curriculum as an effective teaching methodology. Both are perceived equally good in improving students' communication skills. Few aspects of critical thinking are improved more by role plays compared to debate and vice versa. © 2018 by The International Union of Biochemistry and Molecular Biology, 2018. © 2018 The International Union of Biochemistry and Molecular Biology.

Critical role of non-muscle myosin light chain kinase in thrombin-induced endothelial cell inflammation and lung PMN infiltration.

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Fazal, Fabeha; Bijli, Kaiser M; Murrill, Matthew; Leonard, Antony; Minhajuddin, Mohammad; Anwar, Khandaker N; Finkelstein, Jacob N; Watterson, D Martin; Rahman, Arshad

2013-01-01

The pathogenesis of acute lung injury (ALI) involves bidirectional cooperation and close interaction between inflammatory and coagulation pathways. A key molecule linking coagulation and inflammation is the procoagulant thrombin, a serine protease whose concentration is elevated in plasma and lavage fluids of patients with ALI and acute respiratory distress syndrome (ARDS). However, little is known about the mechanism by which thrombin contributes to lung inflammatory response. In this study, we developed a new mouse model that permits investigation of lung inflammation associated with intravascular coagulation. Using this mouse model and in vitro approaches, we addressed the role of non-muscle myosin light chain kinase (nmMLCK) in thrombin-induced endothelial cell (EC) inflammation and lung neutrophil (PMN) infiltration. Our in vitro experiments revealed a key role of nmMLCK in ICAM-1 expression by its ability to control nuclear translocation and transcriptional capacity of RelA/p65 in EC. When subjected to intraperitoneal thrombin challenge, wild type mice showed a marked increase in lung PMN infiltration via expression of ICAM-1. However, these responses were markedly attenuated in mice deficient in nmMLCK. These results provide mechanistic insight into lung inflammatory response associated with intravascular coagulation and identify nmMLCK as a critical target for modulation of lung inflammation.

Frank A. Beach award: programming of neuroendocrine function by early-life experience: a critical role for the immune system.

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Bilbo, Staci D

2013-05-01

Many neuropsychiatric disorders are associated with a strong dysregulation of the immune system, and several have a striking etiology in development as well. Our recent evidence using a rodent model of neonatal Escherichia coli infection has revealed novel insight into the mechanisms underlying cognitive deficits in adulthood, and suggests that the early-life immune history of an individual may be critical to understanding the relative risk of developing later-life mental health disorders in humans. A single neonatal infection programs the function of immune cells within the brain, called microglia, for the life of the rodent such that an adult immune challenge results in exaggerated cytokine production within the brain and associated cognitive deficits. I describe the important role of the immune system, notably microglia, during brain development, and discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, and cognition. Copyright © 2013 Elsevier Inc. All rights reserved.

Critical thinking of destabilizing interpretations of events and phenomena: the role of economic sciences

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Тетяна Андріївна Непокупна

2015-03-01

Full Text Available This article analyzes the global transformations and their impact on the main society life; the specifics of modern interpretations of events and phenomena, their destabilizing effects on behavior, health and life of humans; the role of economic sciences in the formation of critical thinking as a means of combating ignorance and propaganda, formation of an objective world view that grounded on knowledge

Torn between dual roles: the experiences of nurse-family members when a loved one is hospitalised in a critical condition.

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Giles, Tracey M; Williamson, Victoria

2015-11-01

To understand and interpret the experiences of nurse-family members when a family member or loved one is hospitalised in a critical condition. Having a family member hospitalised with a critical illness is a traumatic stressor, often with long-term sequelae. Providing holistic care for family members who are also nurses makes the provision of care more complex because of their professional expertise; yet few studies have explored this issue. In this descriptive study, qualitative data were collected using a questionnaire and analysed using van Manen's (Researching Lived Experience: Human Science for an Action Sensitive Pedagogy, 1990, State University of New York Press, London, ON) six-step approach. Twenty nurse-family members completed an online questionnaire in June 2013. Qualitative findings from 19 participants were included in the analysis. The phenomenological analysis approach described by van Manen (Researching Lived Experience: Human Science for an Action Sensitive Pedagogy, 1990, State University of New York Press, London, ON) was used to describe and interpret nurse-family member experiences. Nurse-family members experience significant dual role conflicts between their personal and professional personas due to their specialised knowledge, need for watchfulness and competing expectations. Our findings describe how dual role conflicts developed and were managed, and reveal the resultant emotional toll and psychological distress as nurse-family members struggled to resolve these conflicts. Nurse-family members require a different type of care than general public family members, yet their unique needs are often unmet, leading to increased anxiety and distress that could potentially be minimised. An increased awareness and emphasis on the nurse-family member experience can ensure health care professionals are better placed to provide appropriate and targeted care to minimise distressing dual role conflicts. There is a need for targeted and specialised

On the Critical Role of Divergent Selection in Evolvability

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Joel Lehman

2016-08-01

Full Text Available An ambitious goal in evolutionary robotics is to evolve increasingly complex robotic behaviors with minimal human design effort. Reaching this goal requires evolutionary algorithms that can unlock from genetic encodings their latent potential for evolvability. One issue clouding this goal is conceptual confusion about evolvability, which often obscures the aspects of evolvability that are important or desirable. The danger from such confusion is that it may establish unrealistic goals for evolvability that prove unproductive in practice. An important issue separate from conceptual confusion is the common misalignment between selection and evolvability in evolutionary robotics. While more expressive encodings can represent higher-level adaptations (e.g. sexual reproduction or developmental systems that increase long-term evolutionary potential (i.e. evolvability, realizing such potential requires gradients of fitness and evolvability to align. In other words, selection is often a critical factor limiting increasing evolvability. Thus, drawing from a series of recent papers, this article seeks to both (1 clarify and focus the ways in which the term evolvability is used within artificial evolution, and (2 argue for the importance of one type of selection, i.e. divergent selection, for enabling evolvability. The main argument is that there is a fundamental connection between divergent selection and evolvability (on both the individual and population level that does not hold for typical goal-oriented selection. The conclusion is that selection pressure plays a critical role in realizing the potential for evolvability, and that divergent selection in particular provides a principled mechanism for encouraging evolvability in artificial evolution.

Exploring critical thinking in critical care nursing education: a pilot study.

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Rogal, Sonya M; Young, Jeanne

2008-01-01

Critical care nurses process vast amounts of information and require well developed critical-thinking skills to make clinical decisions. Using a pretest posttest design, the critical-thinking skills of 31 postgraduate nurses were evaluated using the California Critical Thinking Skills Test (CCTST). For the total group, mean critical-thinking scores improved slightly over time. The CCTST revealed a mean pretest score of 18.5 and a mean posttest score of 19.7, both of which were higher than the established norms for the test. Overall, no significant difference was observed between pretest and posttest. However, statistical significance was observed posttest for nurses whose critical-thinking scores improved (p critical-thinking skills during the course of their study.

The Critical Advantage: Developing Critical Thinking Skills in School

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Gormley, William T., Jr.

2017-01-01

In "The Critical Advantage," noted scholar and early childhood expert William T. Gormley, Jr. takes a wide ranging look at the important role of critical thinking in preparing students for college, careers, and civic life. Drawing on research from psychology, philosophy, business, political science, neuroscience, and other disciplines,…

Infection Reveals a Modification of SIRT2 Critical for Chromatin Association

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Jorge M. Pereira

2018-04-01

Full Text Available Summary: Sirtuin 2 is a nicotinamide-adenine-dinucleotide-dependent deacetylase that regulates cell processes such as carcinogenesis, cell cycle, DNA damage, and infection. Subcellular localization of SIRT2 is crucial for its function but is poorly understood. Infection with the bacterial pathogen Listeria monocytogenes, which relocalizes SIRT2 from the cytoplasm to the chromatin, provides an ideal stimulus for the molecular study of this process. In this report, we provide a map of SIRT2 post-translational modification sites and focus on serine 25 phosphorylation. We show that infection specifically induces dephosphorylation of S25, an event essential for SIRT2 chromatin association. Furthermore, we identify a nuclear complex formed by the phosphatases PPM1A and PPM1B, with SIRT2 essential for controlling H3K18 deacetylation and SIRT2-mediated gene repression during infection and necessary for a productive Listeria infection. This study reveals a molecular mechanism regulating SIRT2 function and localization, paving the way for understanding other SIRT2-regulated cellular processes. : Sirtuins are enzymes critical for various processes, including genomic stability, metabolism, and aging. Through study of Listeria monocytogenes, a bacterial pathogen that exploits SIRT2 for productive infection, Pereira et al. uncover a SIRT2 modification necessary for chromatin association and function. Keywords: chromatin, sirtuin, Listeria monocytogenes, phosphorylation, PPM1, histone acetylation, H3K18, infection, subcellular localization

The Possibility of Film Criticism.

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Poague, Leland; Cadbury, William

1989-01-01

Examines the role of critical language in film criticism. Compares and contrasts Monroe Beardsley's philosophy on film aesthetics with the New Criticism. Outlines some of the contributions Beardsley has made to the study of film criticism. (KM)

Can We Protect the Gut in Critical Illness: The Role of Growth Factors and Other Novel Approaches

OpenAIRE

Dominguez, Jessica A.; Coopersmith, Craig M.

2010-01-01

The intestine plays a central role in the pathophysiology of critical illness and is frequently called the “motor” of the systemic inflammatory response. Perturbations to the intestinal barrier can lead to distant organ damage and multiple organ failure. Therefore, identifying ways to preserve intestinal integrity may be of paramount importance. Growth factors and other peptides have emerged as potential tools for modulation of intestinal inflammation and repair due to their roles in cellular...

‘Promising Spaces’: Universities’ Critical-Moral Mission and Educative Function

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Monica McLean

2015-12-01

Full Text Available Attention has been drawn to a hollowing out of universities' purposes to serve economic interests only. This dissatisfaction has provoked thinking about how to reclaim a critical moral role for universties in society. Inspired by contemporary utopian studies the paper brings together traditional ideas about how transmitting university knowledge connects to universities' critical-moral functions; Amartya Sen and Martha Nussbaum's capabilities approach adapted for education; and Bernstein's theories about knowledge distribution. Focusing on the educative function, the aim is to develop a theoretically informed and practical vision of a university education, which is both personally transformative and produces critical citizens and workers. Research evidence from two projects on university education reveals 'promising spaces' (Cooper, 2014. I conclude that there is reason to believe that the transmission and acquisition of knowledge and understanding in specific fields is key to preserving and recreating a critical-moral mission for universities wherever they are in the world, even though current conditions are inclement and unequal.

Critical/non-critical system methodology report

International Nuclear Information System (INIS)

1989-01-01

The method used to determine how the waste Isolation Pilot Plant (WIPP) facilities/systems were classified as critical or non-critical to the receipt of CH waste is described within this report. All WIPP critical facilities/systems are listed in the Operational Readiness Review Dictionary. Using the Final Safety Analysis Report (FSAR) as a guide to define the boundaries of the facilities/systems, a direct correlation of the ORR Dictionary to the FSAR can be obtained. The critical facilities/systems are those which are directly related to or have a critical support role in the receipt of CH waste. The facility/systems must meet one of the following requirements to be considered critical: (a) confinement or measure of the release of radioactive materials; (b) continued receipt and/or storage of transuranic waste (TRU) without an interruption greater than one month according to the shipping plan schedule; (c) the environmental and occupational safety of personnel meets the established site programs; and (d) the physical security of the WIPP facilities

Critical thinking in nurse managers.

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Zori, Susan; Morrison, Barbara

2009-01-01

Formal education and support is needed for nurse managers to effectively function in their role in the current health care environment. Many nurse managers assume their positions based on expertise in a clinical role with little expertise in managerial and leadership skills. Operating as a manager and leader requires ongoing development of critical thinking skills and the inclination to use those skills. Critical thinking can have a powerful influence on the decision making and problem solving that nurse managers are faced with on a daily basis. The skills that typify critical thinking include analysis, evaluation, inference, and deductive and inductive reasoning. It is intuitive that nurse managers require both the skills and the dispositions of critical thinking to be successful in this pivotal role at a time of transformation in health care. Incorporating critical thinking into education and support programs for the nurse manager is necessary to position the nurse manager for success.

Role of criticality models in ANSI standards for nuclear criticality safety

International Nuclear Information System (INIS)

Thomas, J.T.

1976-01-01

Two methods used in nuclear criticality safety evaluations in the area of neutron interaction among subcritical components of fissile materials are the solid angle and surface density techniques. The accuracy and use of these models are briefly discussed

A creative analysis of the role of practice development facilitators in a critical care environment

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Tanya Heyns

2017-10-01

Full Text Available Practice development focuses on methods to address the quality of care and advance healthcare practices. The role of practice development facilitators to address challenges of delivering evidence-based person-centred care in the critical care environment was determined by using a nominal group technique. Eleven participants from public and private healthcare services reached consensus on seven clusters: theory-practice application, facilitation of learning, increasing collaboration, effective communication, facilitation of change, time management and role modelling. The clusters were visually represented as a hot air balloon. Competence as facilitators is of vital importance to ensure knowledge translation with the aim to improve quality.

Assessing the scholar CanMEDS role in residents using critical appraisal techniques

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Aliya Kassam

2013-03-01

Full Text Available Background: In this brief report, we describe two ways in which we assessed the Scholar CanMEDS role using a method to measure residents’ ability to complete a critical appraisal.  These were incorporated into a modified OSCE format where two stations consisted of 1 critically appraising an article and 2 critiquing an abstract. Method: Residents were invited to participate in the CanMEDS In-Training Exam (CITE through the Office of Postgraduate Medical Education. Mean scores for the two Scholar stations were calculated using the number of correct responses out of 10. The global score represented the examiner’s overall impression of the resident’s knowledge and effort.  Correlations between scores are also presented between the two Scholar stations and a paired sample t-test comparing the global mean scores of the two stations was also performed. Results: Sixty-three of the 64 residents registered to complete the CanMEDS In-Training Exam including the two Scholar stations.  There were no significant differences between the global scores of the Scholar stations showing that the overall knowledge and effort of the residents was similar across both stations (3.8 vs. 3.5, p = 0.13.  The correlation between the total mean scores of both stations (inter-station reliability was also non-significant (r = 0.05, p = 0.67.  No significant differences between senior residents and junior residents were detected or between internal medicine residents and non-internal medicine residents. Conclusion: Further testing of these stations is needed and other novel ways of assessing the Scholar role competencies should also be investigated.

Distress in couples coping with cancer : A meta-analysis and critical review of role and gender effects

NARCIS (Netherlands)

Hagedoorn, Mariet; Sanderman, Robbert; Bolks, Hilde N.; Tuinstra, Jolanda; Coyne, James C.

Research concerning distress in couples coping with cancer was integrated using meta-analysis and narrative critical appraisal. Individual levels of distress were determined more by gender than by the role of being the person with cancer versus that person's partner. That is, women reported

Genome-wide analyses reveal a role for peptide hormones in planarian germline development.

Directory of Open Access Journals (Sweden)

James J Collins

Full Text Available Bioactive peptides (i.e., neuropeptides or peptide hormones represent the largest class of cell-cell signaling molecules in metazoans and are potent regulators of neural and physiological function. In vertebrates, peptide hormones play an integral role in endocrine signaling between the brain and the gonads that controls reproductive development, yet few of these molecules have been shown to influence reproductive development in invertebrates. Here, we define a role for peptide hormones in controlling reproductive physiology of the model flatworm, the planarian Schmidtea mediterranea. Based on our observation that defective neuropeptide processing results in defects in reproductive system development, we employed peptidomic and functional genomic approaches to characterize the planarian peptide hormone complement, identifying 51 prohormone genes and validating 142 peptides biochemically. Comprehensive in situ hybridization analyses of prohormone gene expression revealed the unanticipated complexity of the flatworm nervous system and identified a prohormone specifically expressed in the nervous system of sexually reproducing planarians. We show that this member of the neuropeptide Y superfamily is required for the maintenance of mature reproductive organs and differentiated germ cells in the testes. Additionally, comparative analyses of our biochemically validated prohormones with the genomes of the parasitic flatworms Schistosoma mansoni and Schistosoma japonicum identified new schistosome prohormones and validated half of all predicted peptide-encoding genes in these parasites. These studies describe the peptide hormone complement of a flatworm on a genome-wide scale and reveal a previously uncharacterized role for peptide hormones in flatworm reproduction. Furthermore, they suggest new opportunities for using planarians as free-living models for understanding the reproductive biology of flatworm parasites.

Hypomorphic conditional deletion of E11/Podoplanin reveals a role in osteocyte dendrite elongation.

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Staines, Katherine A; Javaheri, Behzad; Hohenstein, Peter; Fleming, Robert; Ikpegbu, Ekele; Unger, Erin; Hopkinson, Mark; Buttle, David J; Pitsillides, Andrew A; Farquharson, Colin

2017-11-01

The transmembrane glycoprotein E11/Podoplanin (Pdpn) has been implicated in the initial stages of osteocyte differentiation. However, its precise function and regulatory mechanisms are still unknown. Due to the known embryonic lethality induced by global Pdpn deletion, we have herein explored the effect of bone-specific Pdpn knockdown on osteocyte form and function in the post-natal mouse. Extensive skeletal phenotyping of male and female 6-week-old Oc-cre;Pdpn flox/flox (cKO) mice and their Pdpn flox/flox controls (fl/fl) has revealed that Pdpn deletion significantly compromises tibial cortical bone microarchitecture in both sexes, albeit to different extents (p < 0.05). Consistent with this, we observed an increase in stiffness in female cKO mice in comparison to fl/fl mice (p < 0.01). Moreover, analysis of the osteocyte phenotype by phalloidin staining revealed a significant decrease in the dendrite volume (p < 0.001) and length (p < 0.001) in cKO mice in which deletion of Pdpn also modifies the bone anabolic loading response (p < 0.05) in comparison to age-matched fl/fl mice. Together, these data confirm a regulatory role for Pdpn in osteocyte dendrite formation and as such, in the control of osteocyte function. As the osteocyte dendritic network is known to play vital roles in regulating bone modeling/remodeling, this highlights an essential role for Pdpn in bone homeostasis. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

Architect Critical Challenges as a Project Manager in Construction Projects: A Case Study

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Mohammadreza Yadollahi

2014-01-01

Full Text Available All construction professionals such as civil, mechanical, and electrical engineers, quantity surveyors, and architects have important roles in the construction process. Among these, architects are frequently appointed as a project manager (PM. The role of a PM will drive the success of the projects implementation. Therefore, the capability of an architect as a PM (ArPM is critical in reducing challenges encountered. Accordingly, the identification of these challenges is an important task in selecting an appropriate ArPM. The aim of this study is to identify the most critical challenges faced by an ArPM for construction projects. The data were collected through questionnaires and interviews with architects and professionals in the Malaysian construction industry. Because of the fuzziness and uncertainty of subjective responses, Fuzzy Set Ttheory is applied to identify critical challenges. A total of 65 questionnaires were distributed and 36 questionnaires were returned. The results revealed that the critical challenges faced by an ArPM are “poor planning,” “unfamiliar technology,” “unfamiliarity with green buildings and materials,” “inappropriate scheduling,” and “poor workmanship.” All critical challenges were then categorized into six main groups including technical, managerial, personal skills, contractual, psychological, and financial.

Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation.

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Zhang, Guoqi; Yang, Li; Kim, Gab Seok; Ryan, Kieran; Lu, Shulin; O'Donnell, Rebekah K; Spokes, Katherine; Shapiro, Nathan; Aird, William C; Kluk, Michael J; Yano, Kiichiro; Sanchez, Teresa

2013-07-18

The endothelium, as the interface between blood and all tissues, plays a critical role in inflammation. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid, highly abundant in plasma, that potently regulates endothelial responses through interaction with its receptors (S1PRs). Here, we studied the role of S1PR2 in the regulation of the proadhesion and proinflammatory phenotype of the endothelium. By using genetic approaches and a S1PR2-specific antagonist (JTE013), we found that S1PR2 plays a key role in the permeability and inflammatory responses of the vascular endothelium during endotoxemia. Experiments with bone marrow chimeras (S1pr2(+/+) → S1pr2(+/+), S1pr2(+/+) → S1pr2(-/-), and S1pr2(-/-) → S1pr2(+/+)) indicate the critical role of S1PR2 in the stromal compartment, in the regulation of vascular permeability and vascular inflammation. In vitro, JTE013 potently inhibited tumor necrosis factor α-induced endothelial inflammation. Finally, we provide detailed mechanisms on the downstream signaling of S1PR2 in vascular inflammation that include the activation of the stress-activated protein kinase pathway that, together with the Rho-kinase nuclear factor kappa B pathway (NF-kB), are required for S1PR2-mediated endothelial inflammatory responses. Taken together, our data indicate that S1PR2 is a key regulator of the proinflammatory phenotype of the endothelium and identify S1PR2 as a novel therapeutic target for vascular disorders.

Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets.

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Sun, Na; Keep, Richard F; Hua, Ya; Xi, Guohua

2016-10-01

Sphingolipids are a series of cell membrane-derived lipids which act as signaling molecules and play a critical role in cell death and survival, proliferation, recognition, and migration. Sphingosine-1-phosphate acts as a key signaling molecule and regulates lymphocyte trafficking, glial cell activation, vasoconstriction, endothelial barrier function, and neuronal death pathways which plays a critical role in numerous neurological conditions. Stroke is a second leading cause of death all over the world and effective therapies are still in great demand, including ischemic stroke and hemorrhagic stroke as well as poststroke repair. Significantly, sphingolipid activities change after stroke and correlate with stroke outcome, which has promoted efforts to testify whether the sphingolipid pathway could be a novel therapeutic target in stroke. The sphingolipid metabolic pathway, the connection between the pathway and stroke, as well as therapeutic interventions to manipulate the pathway to reduce stroke-induced brain injury are discussed in this review.

Streptavidin-coated gold nanoparticles: critical role of oligonucleotides on stability and fractal aggregation

Directory of Open Access Journals (Sweden)

Roberta D'Agata

2017-01-01

Full Text Available Gold nanoparticles (AuNPs exhibit unique properties that can be modulated through a tailored surface functionalization, enabling their targeted use in biochemical sensing and medical diagnostics. In particular, streptavidin-modified AuNPs are increasingly used for biosensing purposes. We report here a study of AuNPs surface-functionalized with streptavidin-biotinylated oligonucleotide, focussing on the role played by the oligonucleotide probes in the stabilization/destabilization of the functionalized nanoparticle dispersion. The behaviour of the modified AuNP dispersion as a consequence of the competitive displacement of the biotinylated oligonucleotide has been investigated and the critical role of displaced oligonucletides in triggering the quasi one-dimensional aggregation of nanoparticles is demonstrated for the first time. The thorough understanding of the fundamental properties of bioconjugated AuNPs is of great importance for the design of highly sensitive and reliable functionalized AuNP-based assays.

Critical role of environmental factors in the pathogenesis of psoriasis.

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Zeng, Jinrong; Luo, Shuaihantian; Huang, Yumeng; Lu, Qianjin

2017-08-01

Psoriasis is a common cutaneous disease with multifactorial etiology including genetic and non-genetic factors, such as drugs, smoking, drinking, diet, infection and mental stress. Now, the role of the interaction between environmental factors and genetics are considered to be a main factor in the pathogenesis of psoriasis. However, it is a challenge to explore the mechanisms how the environmental factors break the body balance to affect the onset and development of psoriasis. In this article, we review the pathogenesis of psoriasis and summarize numerous clinical data to reveal the association between environmental factors and psoriasis. In addition, we focus on the mechanisms of environmental risk factors impact on psoriasis and provide a series of potential treatments against environmental risk factors. © 2017 Japanese Dermatological Association.

Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism.

Directory of Open Access Journals (Sweden)

Barbara Witek

Full Text Available Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis.

Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism

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Nord, Christoffer; Ahlgren, Ulf; Eriksson, Maria; Vernersson-Lindahl, Emma; Helland, Åslaug; Alexeyev, Oleg A.; Hallberg, Bengt; Palmer, Ruth H.

2015-01-01

Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis. PMID:25955180

Parental criticism and externalizing behavior problems in adolescents: the role of environment and genotype-environment correlation.

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Narusyte, Jurgita; Neiderhiser, Jenae M; Andershed, Anna-Karin; D'Onofrio, Brian M; Reiss, David; Spotts, Erica; Ganiban, Jody; Lichtenstein, Paul

2011-05-01

Genetic factors are important for the association between parental negativity and child problem behavior, but it is not clear whether this is due to passive or evocative genotype-environment correlation (rGE). In this study, we applied the extended children-of-twins model to directly examine the presence of passive and evocative rGE as well as direct environmental effects in the association between parental criticism and adolescent externalizing problem behavior. The cross-sectional data come from the Twin and Offspring Study in Sweden (N = 909 pairs of adult twins) and from the Twin Study of Child and Adolescent Development (N = 915 pairs of twin children). The results revealed that maternal criticism was primarily due to evocative rGE emanating from their adolescent's externalizing behavior. On the other hand, fathers' critical remarks tended to affect adolescent problem behavior in a direct environmental way. This suggests that previously reported differences in caretaking between mothers and fathers also are reflected in differences in why parenting is associated with externalizing behavior in offspring.

Parental criticism and externalizing behavior problems in adolescents– the role of environment and genotype-environment correlation

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Narusyte, Jurgita; Neiderhiser, Jenae M.; Andershed, Anna-Karin; D’Onofrio, Brian M.; Reiss, David; Spotts, Erica; Ganiban, Jody; Lichtenstein, Paul

2011-01-01

Genetic factors are important for the association between parental negativity and child problem behavior, but it is not clear whether this is dueto passive or evocative genotype-environment correlation (rGE). In this study we applied the extended children-of-twins model to directly examine the presence of passive and evocative rGE as well as direct environmental effects in the association between parental criticism and adolescent externalizing problem behavior. The cross-sectional data come from the Twin and Offspring Study in Sweden (TOSS) (N=909 pairs of adult twins) and from the Twin study of CHild and Adolescent Development (TCHAD) (N=915 pairs of twin children). The results revealed that maternal criticism was primarily due to evocative rGE emanating from their adolescent’s externalizing behavior. On the other hand, fathers’ critical remarks tended to affect adolescent problem behavior in a direct environmental way. This suggests that previously reported differences in caretaking between mothers and fathers also are reflected in differences in why parenting is associated with externalizing behavior in offspring. PMID:21280930

Instructors' Positive Emotions: Effects on Student Engagement and Critical Thinking in U.S. and Chinese Classrooms

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Zhang, Qin; Zhang, Jibiao

2013-01-01

In this study, we used the broaden-and-build theory and emotional response theory as the framework to examine the effects of instructors' positive emotions on student engagement and critical thinking in U.S. and Chinese classrooms, as well as the mediating role of students' positive emotions in their relationships. MANOVA results revealed no…

Dreams, mnemonics, and tuning for criticality.

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Pearlmutter, Barak A; Houghton, Conor J

2013-12-01

According to the tuning-for-criticality theory, the essential role of sleep is to protect the brain from super-critical behaviour. Here we argue that this protective role determines the content of dreams and any apparent relationship to the art of memory is secondary to this.

A critical role of the human hippocampus in an electrophysiological measure of implicit memory

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Addante, Richard James

2015-01-01

The hippocampus has traditionally been thought to be critical for conscious explicit memory but not necessary for unconscious implicit memory processing. In a recent study of a group of mild amnesia patients with evidence of MTL damage limited to the hippocampus, subjects were tested on a direct test of item recognition confidence while electroencephalogram (EEG) was acquired, and revealed intact measures of explicit memory from 400–600ms (mid-frontal old-new effect, FN400). The current investigation re-analyzed this data to study event-related potentials (ERPs) of implicit memory, using a recently developed procedure that eliminated declarative memory differences. Prior ERP findings from this technique were first replicated in two independent matched control groups, which exhibited reliable implicit memory effects in posterior scalp regions from 400–600 msec, which were topographically dissociated from the explicit memory effects of familiarity. However, patients were found to be dramatically impaired in implicit memory effects relative to control subjects, as quantified by a reliable condition × group interaction. Several control analysis were conducted to consider alternative factors that could account for the results, including outliers, sample size, age, or contamination by explicit memory, and each of these factors were systematically ruled out. Results suggest that the hippocampus plays a fundamental role in aspects of memory processing that is beyond conscious awareness. The current findings therefore indicate that both memory systems of implicit and explicit memory may rely upon the same neural structures – but function in different physiological ways. PMID:25562828

Quantitative proteomics of the tonoplast reveals a role for glycolytic enzymes in salt tolerance.

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Barkla, Bronwyn J; Vera-Estrella, Rosario; Hernández-Coronado, Marcela; Pantoja, Omar

2009-12-01

To examine the role of the tonoplast in plant salt tolerance and identify proteins involved in the regulation of transporters for vacuolar Na(+) sequestration, we exploited a targeted quantitative proteomics approach. Two-dimensional differential in-gel electrophoresis analysis of free flow zonal electrophoresis separated tonoplast fractions from control, and salt-treated Mesembryanthemum crystallinum plants revealed the membrane association of glycolytic enzymes aldolase and enolase, along with subunits of the vacuolar H(+)-ATPase V-ATPase. Protein blot analysis confirmed coordinated salt regulation of these proteins, and chaotrope treatment indicated a strong tonoplast association. Reciprocal coimmunoprecipitation studies revealed that the glycolytic enzymes interacted with the V-ATPase subunit B VHA-B, and aldolase was shown to stimulate V-ATPase activity in vitro by increasing the affinity for ATP. To investigate a physiological role for this association, the Arabidopsis thaliana cytoplasmic enolase mutant, los2, was characterized. These plants were salt sensitive, and there was a specific reduction in enolase abundance in the tonoplast from salt-treated plants. Moreover, tonoplast isolated from mutant plants showed an impaired ability for aldolase stimulation of V-ATPase hydrolytic activity. The association of glycolytic proteins with the tonoplast may not only channel ATP to the V-ATPase, but also directly upregulate H(+)-pump activity.

Complementary role of critical integral experiment and power reactor start-up experiments for LMFBR neutronics data and method validation

International Nuclear Information System (INIS)

Salvatores, M.

1986-09-01

Both critical experiments and power reactor results play at present a complementary role in reducing the uncertainties in Key design parameters for LMFBR, which can be relevant for the economic performances of this type of reactors

The Arabidopsis szl1 Mutant Reveals a Critical Role of β-Carotene in Photosystem I Photoprotection1[C][W

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Cazzaniga, Stefano; Li, Zhirong; Niyogi, Krishna K.; Bassi, Roberto; Dall’Osto, Luca

2012-01-01

Carotenes and their oxygenated derivatives, the xanthophylls, are structural determinants in both photosystems (PS) I and II. They bind and stabilize photosynthetic complexes, increase the light-harvesting capacity of chlorophyll-binding proteins, and have a major role in chloroplast photoprotection. Localization of carotenoid species within each PS is highly conserved: Core complexes bind carotenes, whereas peripheral light-harvesting systems bind xanthophylls. The specific functional role of each xanthophyll species has been recently described by genetic dissection, however the in vivo role of carotenes has not been similarly defined. Here, we have analyzed the function of carotenes in photosynthesis and photoprotection, distinct from that of xanthophylls, by characterizing the suppressor of zeaxanthin-less (szl) mutant of Arabidopsis (Arabidopsis thaliana) which, due to the decreased activity of the lycopene-β-cyclase, shows a lower carotene content than wild-type plants. When grown at room temperature, mutant plants showed a lower content in PSI light-harvesting complex I complex than the wild type, and a reduced capacity for chlorophyll fluorescence quenching, the rapidly reversible component of nonphotochemical quenching. When exposed to high light at chilling temperature, szl1 plants showed stronger photoxidation than wild-type plants. Both PSI and PSII from szl1 were similarly depleted in carotenes and yet PSI activity was more sensitive to light stress than PSII as shown by the stronger photoinhibition of PSI and increased rate of singlet oxygen release from isolated PSI light-harvesting complex I complexes of szl1 compared with the wild type. We conclude that carotene depletion in the core complexes impairs photoprotection of both PS under high light at chilling temperature, with PSI being far more affected than PSII. PMID:23029671

The role of the nurse at the end of the life of a critically ill patient.

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González-Rincón, M; Díaz de Herrera-Marchal, P; Martínez-Martín, M L

2018-06-11

Analyze the role of the nurse at the end of the life of a critically ill patient. Bibliographic review from a search of the health science databases such as PubMed, CINAHL, Cuiden, Scopus, Cochrane, as well as specialized platforms, general and thematic browsers. The limits were language (English or Spanish) and publication date (2005-2015). 180 articles met the inclusion criteria, and 16 of them were selected for analysis. The main results were grouped into three categories of analysis: direct patient care, family-focussed care and the nurse's role within the team. the described roles place the nurse as a key element in humanising death in the ICU and so nurses can and must lead change, playing an active role in creating strategies that really promote the integration of a palliative care approach in ICU. Copyright © 2018 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Publicado por Elsevier España, S.L.U. All rights reserved.

Parental verbal abuse and the mediating role of self-criticism in adult internalizing disorders.

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Sachs-Ericsson, Natalie; Verona, Edelyn; Joiner, Thomas; Preacher, Kristopher J

2006-07-01

Researchers (e.g., [Gibb, B.E., 2002. Childhood maltreatment and negative cognitive styles. A quantitative and qualitative review. Clinical Psychology Review, 22 (2), 223-246]; [Rose, D.T., Abramson, L.Y., 1992. Developmental predictors of depressive cognitive styles: developmental perspectives on depression. In Cicchetti, D., Toth, S.L. (Eds.), Developmental Perspectives on Depression. Rochester symposium on developmental psychopathology, vol. 4, pp. 323-349]) have proposed that when childhood abuse is verbal (rather than sexual or physical), the child is more likely to develop a negative self-schema because the negative self-cognitions are directly supplied to the child by the abuser (e.g., "you are stupid"). In a test of this theory in adult participants, and drawing on the National Comorbidity Survey (NCS) (N=5877), we investigate the mediating role of current levels of self-criticism on the relationship between retrospective reports of parental verbal abuse, as well as sexual and physical abuse, and adult internalizing symptoms. We found self-criticism, but not dependency traits, to fully mediate the relationship between childhood verbal abuse perpetrated by parents and internalizing (depression, anxiety) symptoms. On the other hand, self-criticism was only a partial mediator of the relationship between the other types of abuse and internalizing symptoms. The NCS data is cross-sectional, which limits any firm conclusions regarding causality. While these results are suggestive that self-criticism is a mediator of the relationship between abuse and internalizing symptoms, longitudinal data are necessary to help rule out alternative explanations. Results of this study suggest that childhood abuse experiences, and in particular verbal abuse, may confer risk for internalizing disorders in part because verbal abuse influences the development of a self-critical style.

[Critical role of clinical laboratories in hospital infection control].

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Yagi, Tetsuya

2010-11-01

The hospital infection control and prevention is recognized to be more and more important according to the advances in modern medical treatment and care. Clinical microbiology laboratory play critical roles in the hospital infection control as a member of infection control team (ICT). They are the first in a hospital to identify outbreak of MRSA in NICU and molecular epidemiological analysis of the isolates lead proper intervention of ICT to the concerned ward. From a viewpoint of infectious disease specialist, rapid and precise microbiological information is essential for the appropriate diagnosis and treatment of infectious diseases. Each medical technologist need to make efforts to understand the characteristics of the examinations for infectious diseases and send out information useful for clinical practices. In our hospital, with the participation of all members of medical technologists, rapid reporting system was developed for blood culture examinations, which greatly contribute to the appropriate treatment of bloodstream infections. Collaborations of clinical microbiology laboratory with other members of ICT realize high quality hospital infection control. They also need to be aware of themselves as good practitioners of infection control measures to prevent hospital infections.

Serbian music criticism in the first half of the twentieth century: Its canon, its method and its educational role

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Vasić Aleksandar

2008-01-01

Full Text Available Serbian music criticism became a subject of professional music critics at the beginning of the twentieth century, after being developed by music amateurs throughout the whole previous century. The Serbian Literary Magazine (1901- 1914, 1920-1941, the forum of the Serbian modernist writers in the early 1900s, had a crucial role in shaping the Serbian music criticism and essayistics of the modern era. The Serbian elite musicians wrote for the SLM and therefore it reflects the most important issues of the early twentieth century Serbian music. The SLM undertook the mission of educating its readers. The music culture of the Serbian public was only recently developed. The public needed an introduction into the most important features of the European music, as well as developing its own taste in music. This paper deals with two aspects of the music criticism in the SLM, in view of its educational role: the problem of virtuosity and the method used by music critics in this magazine. The aesthetic canon of the SLM was marked by decisively negative attitude towards the virtuosity. Mainly concerned by educating the Serbian music public in the spirit of the highest music achievements in Europe, the music writers of the SLM criticized both domestic and foreign performers who favoured virtuosity over the 'essence' of music. Therefore, Niccolò Paganini, Franz Liszt, and even Peter Tchaikowsky with his Violin concerto became the subject of the magazine's criticism. However their attitude towards the interpreters with both musicality and virtuoso technique was always positive. That was evident in the writings on Jan Kubelík. This educational mission also had its effect on the structure of critique writings in the SLM. In their wish to inform the Serbian public on the European music (which they did very professionally, the critics gave much more information on biographies, bibliographies and style of the European composers, than they valued the interpretation

Critical Factors of E-Learning Adoption and Acceptance in Pakistan: A Literature Review

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F. Kanwal

2017-08-01

Full Text Available This review paper examines the prior studies on critical factors of e-learning adoption in Pakistan. The search terms identified 40 papers reporting 25 conceptual and qualitative and 15 quantitative evidence about the e-learning adoption and critical factors that may influence the adoption of e-learning in Pakistan. The findings revealed that modern paradigm shift requires the in-depth analysis of government policies, institutional and management role, students and faculty attitude, social norms, cultural values as well as technological advancement. These factors may directly or indirectly affect the intention of students towards e-learning adoption. The lack of quantitative evidences illustrate that policy makers, practitioners and researchers need to pay attention for further research of identifying and analyzing the critical factors which enhances the e-learning adoption in Pakistan.

The Dual Role of Vegetation as a Constraint on Mass and Energy Flux into the Critical Zone and as an Emergent Property of Geophysical Critical Zone Structure

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Brooks, P. D.; Swetnam, T. L.; Barnard, H. R.; Singha, K.; Harpold, A.; Litvak, M. E.

2017-12-01

Spatial patterns in vegetation long have been used to scale both landsurface-atmosphere exchanges of water and carbon as well as to infer subsurface structure. These pursuits typical proceed in isolation and rarely do inferences gained from one community propagate to related efforts in another. Perhaps more importantly, vegetation often is treated as an emergent property of landscape-climate interactions rather than an active modifier of both critical zone structure and energy fluxes. We posit that vegetation structure and activity are under utilized as a tool towards understanding landscape evolution and present examples that begin to disentangle the role of vegetation as both an emergent property and an active control on critical zone structure and function. As climate change, population growth, and land use changes threaten water resources worldwide, the need for the new insights vegetation can provide becomes not just a basic science priority, but a pressing applied science question with clear societal importance. This presentation will provide an overview of recent efforts to address the dual role of vegetation in both modifying and reflecting critical zone structure in the western North American forests. For example, interactions between topography and stand scale vegetation structure influence both solar radiation and turbulence altering landscape scale partitioning of evaporation vs transpiration with major impacts of surface water supply. Similarly, interactions between topographic shading, lateral redistribution of plant available water, and subsurface storage create a mosaic of drought resistance and resilience across complex terrain. These complex interactions between geophysical and vegetation components of critical zone structure result in predictable patterns in catchment scale hydrologic partitioning within individual watersheds while simultaneously suggesting testable hypotheses for why catchments under similar climate regimes respond so

Relatives to Critically Ill Patients Have No Sense of Coherence

DEFF Research Database (Denmark)

Laursen, Jannie; Andresen, Kristoffer; Rosenberg, Jacob

2016-01-01

shown that relatives do not always receive the attention they need from health professionals. There is a lack of studies that focus on relatives' satisfaction and involvement during their family members' hospitalization. Design. A mixed methods design was chosen. Methods. A quantitative study...... of the dissatisfaction, a qualitative approach was used and the in-depth interviews revealed three themes: lack of continuity and structure, responsibility of coordination, and relatives feeling left on their own with no guiding and support. Conclusion. Health professionals' key role in relation to relatives must......Aims and Objective. To investigate the relatives' satisfaction and involvement on a general surgery ward regarding the critically ill patient. Introduction. Relatives to critically ill patients are affected both physically and mentally during the hospitalization of a family member. Research has...

Doing "Critical" in a Postfeminist Era: Reviving Critical Consciousness through Peer Dialog

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Lazar, Michelle M.

2014-01-01

Critical language awareness (CLA) has aimed to raise critical consciousness in language education about the social aspects of language use, and especially the relationship between language and power, and is considered to play a significant role in enabling learners to participate effectively in democratic citizenship within and beyond the…

AUTHENTIC TEXTS FOR CRITICAL READING ACTIVITIES

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Ila Amalia

2016-03-01

Full Text Available This research takes an action research aimed at promoting critical reading (“thinking” while reading skills using authentic materials among the students. This research also aims to reveal the students perception on using critical reading skills in reading activities. Nineteen English Education Department students who took Reading IV class, participated in this project. There were three cycles with three different critical reading strategies were applied. Meanwhile, the authentic materials were taken from newspaper and internet articles. The result revealed that the use of critical reading strategies along with the use of authentic materials has improved students’ critical reading skills as seen from the improvement of each cycle - the students critical reading skill was 54% (fair in the cycle 1 improved to 68% (average in cycle 2, and 82% (good in cycle 3.. In addition, based on the critical reading skill criteria, the students’ critical reading skill has improved from 40% (nearly meet to 80% (exceed. Meanwhile, from the students’ perception questionnaire, it was shown that 63% students agreed the critical reading activity using authentic text could improve critical thinking and 58% students agreed that doing critical reading activity could improve reading comprehension. The result had the implication that the use of authentic texts could improve students’ critical reading skills if it was taught by performing not lecturing them. Selectively choosing various strategies and materials can trigger students’ activeness in responding to a text, that eventually shape their critical reading skills.

Recognition of TLR2 N-Glycans: Critical Role in ArtinM Immunomodulatory Activity

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da Silva, Thiago Aparecido; Ruas, Luciana Pereira; Nohara, Lilian L.; de Almeida, Igor Correia; Roque-Barreira, Maria Cristina

2014-01-01

TLR2 plays a critical role in the protection against Paracoccidioides brasiliensis conferred by ArtinM administration. ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus, induces IL-12 production in macrophages and dendritic cells, which accounts for the T helper1 immunity that results from ArtinM administration. We examined the direct interaction of ArtinM with TLR2using HEK293A cells transfected with TLR2, alone or in combination with TLR1 or TLR6, together with accessory proteins. Stimulation with ArtinM induced NF-κB activation and interleukin (IL)-8 production in cells transfected with TLR2, TLR2/1, or TLR2/6. Murine macrophages that were stimulated with ArtinM had augmented TLR2 mRNA expression. Furthermore, pre-incubation of unstimulated macrophages with an anti-TLR2 antibody reduced the cell labeling with ArtinM. In addition, a microplate assay revealed that ArtinM bound to TLR2 molecules that had been captured by specific antibodies from a macrophages lysate. Notably,ArtinM binding to TLR2 was selectively inhibited when the lectin was pre-incubated with mannotriose. The biological relevance of the direct interaction of ArtinM with TLR2 glycans was assessed using macrophages from TLR2-KOmice, which produced significantly lower levels of IL-12 and IL-10 in response to ArtinM than macrophages from wild-type mice. Pre-treatment of murine macrophages with pharmacological inhibitors of signaling molecules demonstrated the involvement of p38 MAPK and JNK in the IL-12 production induced by ArtinM and the involvement ofPI3K in IL-10 production. Thus, ArtinM interacts directly with TLR2 or TLR2 heterodimers in a carbohydrate recognition-dependent manner and functions as a TLR2 agonist with immunomodulatory properties. PMID:24892697

Recognition of TLR2 N-glycans: critical role in ArtinM immunomodulatory activity.

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Vania Sammartino Mariano

Full Text Available TLR2 plays a critical role in the protection against Paracoccidioides brasiliensis conferred by ArtinM administration. ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus, induces IL-12 production in macrophages and dendritic cells, which accounts for the T helper1 immunity that results from ArtinM administration. We examined the direct interaction of ArtinM with TLR2using HEK293A cells transfected with TLR2, alone or in combination with TLR1 or TLR6, together with accessory proteins. Stimulation with ArtinM induced NF-κB activation and interleukin (IL-8 production in cells transfected with TLR2, TLR2/1, or TLR2/6. Murine macrophages that were stimulated with ArtinM had augmented TLR2 mRNA expression. Furthermore, pre-incubation of unstimulated macrophages with an anti-TLR2 antibody reduced the cell labeling with ArtinM. In addition, a microplate assay revealed that ArtinM bound to TLR2 molecules that had been captured by specific antibodies from a macrophages lysate. Notably,ArtinM binding to TLR2 was selectively inhibited when the lectin was pre-incubated with mannotriose. The biological relevance of the direct interaction of ArtinM with TLR2 glycans was assessed using macrophages from TLR2-KOmice, which produced significantly lower levels of IL-12 and IL-10 in response to ArtinM than macrophages from wild-type mice. Pre-treatment of murine macrophages with pharmacological inhibitors of signaling molecules demonstrated the involvement of p38 MAPK and JNK in the IL-12 production induced by ArtinM and the involvement ofPI3K in IL-10 production. Thus, ArtinM interacts directly with TLR2 or TLR2 heterodimers in a carbohydrate recognition-dependent manner and functions as a TLR2 agonist with immunomodulatory properties.

The role of nutritional support in the physical and functional recovery of critically ill patients: a narrative review.

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Bear, Danielle E; Wandrag, Liesl; Merriweather, Judith L; Connolly, Bronwen; Hart, Nicholas; Grocott, Michael P W

2017-08-26

The lack of benefit from randomised controlled trials has resulted in significant controversy regarding the role of nutrition during critical illness in terms of long-term recovery and outcome. Although methodological caveats with a failure to adequately appreciate biological mechanisms may explain these disappointing results, it must be acknowledged that nutritional support during early critical illness, when considered alone, may have limited long-term functional impact.This narrative review focuses specifically on recent clinical trials and evaluates the impact of nutrition during critical illness on long-term physical and functional recovery.Specific focus on the trial design and methodological limitations has been considered in detail. Limitations include delivery of caloric and protein targets, patient heterogeneity, short duration of intervention, inappropriate clinical outcomes and a disregard for baseline nutritional status and nutritional intake in the post-ICU period.With survivorship at the forefront of critical care research, it is imperative that nutrition studies carefully consider biological mechanisms and trial design because these factors can strongly influence outcomes, in particular long-term physical and functional outcome. Failure to do so may lead to inconclusive clinical trials and consequent rejection of the potentially beneficial effects of nutrition interventions during critical illness.

The role of critical thinking skills and learning styles of university students in their academic performance.

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Ghazivakili, Zohre; Norouzi Nia, Roohangiz; Panahi, Faride; Karimi, Mehrdad; Gholsorkhi, Hayede; Ahmadi, Zarrin

2014-07-01

The Current world needs people who have a lot of different abilities such as cognition and application of different ways of thinking, research, problem solving, critical thinking skills and creativity. In addition to critical thinking, learning styles is another key factor which has an essential role in the process of problem solving. This study aimed to determine the relationship between learning styles and critical thinking of students and their academic performance in Alborz University of Medical Science. This cross-correlation study was performed in 2012, on 216 students of Alborz University who were selected randomly by the stratified random sampling. The data was obtained via a three-part questionnaire included demographic data, Kolb standardized questionnaire of learning style and California critical thinking standardized questionnaire. The academic performance of the students was extracted by the school records. The validity of the instruments was determined in terms of content validity, and the reliability was gained through internal consistency methods. Cronbach's alpha coefficient was found to be 0.78 for the California critical thinking questionnaire. The Chi Square test, Independent t-test, one way ANOVA and Pearson correlation test were used to determine relationship between variables. The Package SPSS14 statistical software was used to analyze data with a significant level of pstudents with convergent learning style have better performance than other groups. Also learning style had a relationship with age, gender, field of study, semester and job. The results about the critical thinking of the students showed that the mean of deductive reasoning and evaluation skills were higher than that of other skills and analytical skills had the lowest mean and there was a positive significant relationship between the students' performance with inferential skill and the total score of critical thinking skills (pskills and deductive reasoning had significant

Voltage Imaging of Waking Mouse Cortex Reveals Emergence of Critical Neuronal Dynamics

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Scott, Gregory; Fagerholm, Erik D.; Mutoh, Hiroki; Leech, Robert; Sharp, David J.; Shew, Woodrow L.

2014-01-01

Complex cognitive processes require neuronal activity to be coordinated across multiple scales, ranging from local microcircuits to cortex-wide networks. However, multiscale cortical dynamics are not well understood because few experimental approaches have provided sufficient support for hypotheses involving multiscale interactions. To address these limitations, we used, in experiments involving mice, genetically encoded voltage indicator imaging, which measures cortex-wide electrical activity at high spatiotemporal resolution. Here we show that, as mice recovered from anesthesia, scale-invariant spatiotemporal patterns of neuronal activity gradually emerge. We show for the first time that this scale-invariant activity spans four orders of magnitude in awake mice. In contrast, we found that the cortical dynamics of anesthetized mice were not scale invariant. Our results bridge empirical evidence from disparate scales and support theoretical predictions that the awake cortex operates in a dynamical regime known as criticality. The criticality hypothesis predicts that small-scale cortical dynamics are governed by the same principles as those governing larger-scale dynamics. Importantly, these scale-invariant principles also optimize certain aspects of information processing. Our results suggest that during the emergence from anesthesia, criticality arises as information processing demands increase. We expect that, as measurement tools advance toward larger scales and greater resolution, the multiscale framework offered by criticality will continue to provide quantitative predictions and insight on how neurons, microcircuits, and large-scale networks are dynamically coordinated in the brain. PMID:25505314

Critical technologies: The role of chemistry and chemical engineering

International Nuclear Information System (INIS)

1992-01-01

The purpose of this report is to identify and illustrate key contributions of chemical and chemical engineering research to the development of technologies that have been deemed critical to the economy, security, and well-being of our nation. The report surveys a wide range of vital technologies that are heavily reliant or even critically dependent on chemical or chemical engineering research. Examples were taken from the fields of materials, manufacturing, energy, transportation, public health, information and communications, and the environment. While loosely following the structure of the critical technologies report of the NCTP, our committee decided on a different approach, that of using examples backed up by extensive illustrations

Bim: guardian of tissue homeostasis and critical regulator of the immune system, tumorigenesis and bone biology.

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Akiyama, Toru; Tanaka, Sakae

2011-08-01

One of the most important roles of apoptosis is the maintenance of tissue homeostasis. Impairment of apoptosis leads to a number of pathological conditions. In response to apoptotic signals, various proteins are activated in a pathway and signal-specific manner. Recently, the pro-apoptotic molecule Bim has attracted increasing attention as a pivotal regulator of tissue homeostasis. The Bim expression level is strictly controlled in both transcriptional and post-transcriptional levels. This control is dependent on cell, tissue and apoptotic stimuli. The phenotype of Bim-deficient mice is a systemic lupus erythematosus-like autoimmune disease with an abnormal accumulation of hematopoietic cells. Bim is thus a critical regulator of hematopoietic cells and immune system. Further studies have revealed the critical roles of Bim in various normal and pathological conditions, including bone homeostasis and tumorigenesis. The current understanding of Bim signaling and roles in the maintenance of tissue homeostasis is reviewed in this paper, focusing on the immune system, bone biology and tumorigenesis to illustrate the diversified role of Bim.

The Effect of Teaching Critical Thinking on Al-Buraimi University College students’ Writing Skills: A Case Study

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Yahia Ashour Mohammed AlKhoudary

2015-11-01

Full Text Available This study explores the role of writing in developing students’ critical thinking. It also sheds light on traditional writing assignments which fail to help students develop their comprehension of course content and evaluate their writing products critically. Moreover, this probe is to discover learners and teachers’ attitude towards the role of critical thinking in promoting the writing skills at AlBuraimi University College (BUC. The result of this study focuses on the effect of integrating critical thinking on learners’ performance. The procedure of this investigation is based on a combination of qualitative, quantitative (1 one hundred students who are taking writing course are selected randomly and divided into two groups; (2 pre- and posttests conducted to both groups; (3 twenty teachers were selected randomly (10 males and 10 females; questionnaires are administered to EFL teachers at BUC. The findings of this study illustrate that students who write critically are mostly motivated and their performance is affected positively. It also reveals that there are significant differences in posttest scores between treatment and controlled group. Moreover, teachers’ response to questionnaire supports the idea of integrating critical thinking in teaching the writing skills at BUC. Thus, is recommended that teachers should use thinking skills to enhance students’ writing performance and creativity.

Memory Erasure Experiments Indicate a Critical Role of CaMKII in Memory Storage.

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Rossetti, Tom; Banerjee, Somdeb; Kim, Chris; Leubner, Megan; Lamar, Casey; Gupta, Pooja; Lee, Bomsol; Neve, Rachael; Lisman, John

2017-09-27

The abundant synaptic protein CaMKII is necessary for long-term potentiation (LTP) and memory. However, whether CaMKII is required only during initial processes or whether it also mediates memory storage remains unclear. The most direct test of a storage role is the erasure test. In this test, a putative memory molecule is inhibited after learning. The key prediction is that this should produce persistent memory erasure even after the inhibitory agent is removed. We conducted this test using transient viral (HSV) expression of dominant-negative CaMKII-alpha (K42M) in the hippocampus. This produced persistent erasure of conditioned place avoidance. As an additional test, we found that expression of activated CaMKII (T286D/T305A/T306A) impaired place avoidance, a result not expected if a process other than CaMKII stores memory. Our behavioral results, taken together with prior experiments on LTP, strongly support a critical role of CaMKII in LTP maintenance and memory storage. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of critical thinking skills and learning styles of university students in their academic performance

Science.gov (United States)

GHAZIVAKILI, ZOHRE; NOROUZI NIA, ROOHANGIZ; PANAHI, FARIDE; KARIMI, MEHRDAD; GHOLSORKHI, HAYEDE; AHMADI, ZARRIN

2014-01-01

Introduction: The Current world needs people who have a lot of different abilities such as cognition and application of different ways of thinking, research, problem solving, critical thinking skills and creativity. In addition to critical thinking, learning styles is another key factor which has an essential role in the process of problem solving. This study aimed to determine the relationship between learning styles and critical thinking of students and their academic performance in Alborz University of Medical Science. Methods: This cross-correlation study was performed in 2012, on 216 students of Alborz University who were selected randomly by the stratified random sampling. The data was obtained via a three-part questionnaire included demographic data, Kolb standardized questionnaire of learning style and California critical thinking standardized questionnaire. The academic performance of the students was extracted by the school records. The validity of the instruments was determined in terms of content validity, and the reliability was gained through internal consistency methods. Cronbach's alpha coefficient was found to be 0.78 for the California critical thinking questionnaire. The Chi Square test, Independent t-test, one way ANOVA and Pearson correlation test were used to determine relationship between variables. The Package SPSS14 statistical software was used to analyze data with a significant level of pcritical thinking of the students showed that the mean of deductive reasoning and evaluation skills were higher than that of other skills and analytical skills had the lowest mean and there was a positive significant relationship between the students’ performance with inferential skill and the total score of critical thinking skills (pcritical thinking had significant difference between different learning styles. Conclusion: The results of this study showed that the learning styles, critical thinking and academic performance are significantly associated

Critical state transformation in hard superconductors resulting from thermomagnetic avalanches

International Nuclear Information System (INIS)

Chabanenko, V.V.; Kuchuk, E.I.; Rusakov, V.F.; Abaloszewa, I.; Nabialek, A.; Perez-Rodriguez, F.

2016-01-01

The results of experimental investigations of magnetic flux dynamics in finite superconductors, obtained using integral and local measurements methods, are presented. Local methods were aimed at clarifying the role of demagnetizing factor in dynamic formation of a complex magnetic structure of the critical state of hard superconductors. To understand the reasons for cardinal restructuring of the induction, we further analyzed the literature data of flux dynamics visualization during avalanches, obtained by magneto-optical methods. New features in the behavior of the magnetic flux during and after the avalanche were discovered. Two stages of the formation of the induction structures in the avalanche area were established, i.e. of homogeneous and heterogeneous filling with the magnetic flux. The mechanism of the inversion of the induction profile was considered. Oscillations in the speed of the front of the magnetic flux were revealed. Transformation of the critical state near the edge of the sample was analyzed. The role of thermal effects and of de-magnetizing factor in the dissipative flux dynamics was shown. Generalized information allowed, in the framework of the Bean concept, to present a model the transformation of the picture of the induction of the critical state and of the superconducting currents of a finite superconductor as a result of flux avalanches for two regimes - of screening and trapping of the magnetic flux.

New inducible genetic method reveals critical roles of GABA in the control of feeding and metabolism.

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Meng, Fantao; Han, Yong; Srisai, Dollada; Belakhov, Valery; Farias, Monica; Xu, Yong; Palmiter, Richard D; Baasov, Timor; Wu, Qi

2016-03-29

Currently available inducible Cre/loxP systems, despite their considerable utility in gene manipulation, have pitfalls in certain scenarios, such as unsatisfactory recombination rates and deleterious effects on physiology and behavior. To overcome these limitations, we designed a new, inducible gene-targeting system by introducing an in-frame nonsense mutation into the coding sequence of Cre recombinase (nsCre). Mutant mRNAs transcribed from nsCre transgene can be efficiently translated into full-length, functional Cre recombinase in the presence of nonsense suppressors such as aminoglycosides. In a proof-of-concept model, GABA signaling from hypothalamic neurons expressing agouti-related peptide (AgRP) was genetically inactivated within 4 d after treatment with a synthetic aminoglycoside. Disruption of GABA synthesis in AgRP neurons in young adult mice led to a dramatic loss of body weight due to reduced food intake and elevated energy expenditure; they also manifested glucose intolerance. In contrast, older mice with genetic inactivation of GABA signaling by AgRP neurons had only transient reduction of feeding and body weight; their energy expenditure and glucose tolerance were unaffected. These results indicate that GABAergic signaling from AgRP neurons plays a key role in the control of feeding and metabolism through an age-dependent mechanism. This new genetic technique will augment current tools used to elucidate mechanisms underlying many physiological and neurological processes.

Autophagy plays a critical role in ChLym-1-induced cytotoxicity of non-hodgkin's lymphoma cells.

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Jiajun Fan

Full Text Available Autophagy is a critical mechanism in both cancer therapy resistance and tumor suppression. Monoclonal antibodies have been documented to kill tumor cells via apoptosis, antibody-dependent cellular cytotoxicity (ADCC and complement-dependent cytotoxicity (CDC. In this study, we report for the first time that chLym-1, a chimeric anti-human HLA-DR monoclonal antibody, induces autophagy in Raji Non-Hodgkin's Lymphoma (NHL cells. Interestingly, inhibition of autophagy by pharmacological inhibitors (3-methyladenine and NH4Cl or genetic approaches (siRNA targeting Atg5 suppresses chLym-1-induced growth inhibition, apoptosis, ADCC and CDC in Raji cells, while induction of autophagy could accelerate cytotoxic effects of chLym-1 on Raji cells. Furthermore, chLym-1-induced autophagy can mediate apoptosis through Caspase 9 activation, demonstrating the tumor-suppressing role of autophagy in antilymphoma effects of chLym-1. Moreover, chLym-1 can activate several upstream signaling pathways of autophagy including Akt/mTOR and extracellular signal-regulated kinase 1/2 (Erk1/2. These results elucidate the critical role of autophagy in cytotoxicity of chLym-1 antibody and suggest a potential therapeutic strategy of NHL therapy by monoclonal antibody chLym-1 in combination with autophagy inducer.

Journal writing in science: Effects on comprehension, interest, and critical reflection

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Kristin Wäschle

2015-06-01

Full Text Available Writing-to-learn assignments typically foster deep comprehension of learning contents. Journal writing, in particular, promotes the application of learning strategies, which promote learners’ comprehension, interest in a topic and ability to critically reflect on learning contents. Against this background, we conducted two longitudinal field studies. In Study 1, twenty-one students wrote learning journal entries after their biology lessons. After the intervention period, they showed better scores in comprehension, interest and critical reflection than the control class, in which students (n=25 completed other homework assignments. Mediation analyses revealed a domino effect: Journal writing improved comprehension, which led to raised interest, which resulted in superior critical reflection. Study 2 further investigated the role of learners’ interest in improving critical reflection. Students in the experimental condition (n=13 received a personal-utility prompt in addition to cognitive and metacognitive prompts to support journal writing. In the control group (n=11, students only received cognitive and metacognitive prompts. The experimental group showed higher interest scores after the intervention period and a better quality of critical reflections on a bio-ethical issue than the control group. Together, these studies illustrate the potentials of journal writing for improving learners’ comprehension, their interest and ability to critically reflect on complex scientific issues.

Disruption of Msx-1 and Msx-2 reveals roles for these genes in craniofacial, eye, and axial development.

Science.gov (United States)

Foerst-Potts, L; Sadler, T W

1997-05-01

In mouse embryos, the muscle segment homeobox genes, Msx-1 and Msx-2 are expressed during critical stages of neural tube, neural crest, and craniofacial development, suggesting that these genes play important roles in organogenesis and cell differentiation. Although the patterns of expression are intriguing, little is known about the function of these genes in vertebrate embryonic development. Therefore, the expression of both genes, separately and together, was disrupted using antisense oligodeoxynucleotides and whole embryo culture techniques. Antisense attenuation of Msx-1 during early stages of neurulation produced hypoplasia of the maxillary, mandibular, and frontonasal prominences, eye anomalies, and somite and neural tube abnormalities. Eye defects consisted of enlarged optic vesicles, which may ultimately result in micropthalmia similar to that observed in Small eye mice homozygous for mutations in the Pax-6 gene. Histological sections and SEM analysis revealed a thinning of the neuroepithelium in the diencephalon and optic vesicle and mesenchymal deficiencies in the craniofacial region. Injections of Msx-2 antisense oligodeoxynucleotides produced similar malformations as those targeting Msx-1, with the exception that there was an increase in number and severity of neural tube and somite defects. Embryos injected with the combination of Msx-1 + Msx-2 antisense oligodeoxynucleotides showed no novel abnormalities, suggesting that the genes do not operate in a redundant manner.

Eco-criticism and Italo Calvino: A Literature Which Serves the Environment

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Fatemeh Asgari

2018-02-01

Full Text Available Eco-criticism, a branch of modern literary criticism, nowadays everywhere in the world, from West to East, and in the form of a cultural and moral flow, through literature announces its message as an alarm, a concern for the environment. Among the writers of contemporary Italian Literature, Italo Calvino is the first ecologic story-teller, who beyond his short stories reveals the emergency situation of urban ecosystem. The first character of his stories, condemned to live in industrial cities, is looking at nature disappearing in his smoky hands. The present article, through the content analysis of some of these works, points out to the important role of Literature which serves in the cultivation for preserving the environment and awakening the minds of humen against a serious danger that threatens their lives.

Dissecting a role for melanopsin in behavioural light aversion reveals a response independent of conventional photoreception.

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Ma'ayan Semo

Full Text Available Melanopsin photoreception plays a vital role in irradiance detection for non-image forming responses to light. However, little is known about the involvement of melanopsin in emotional processing of luminance. When confronted with a gradient in light, organisms exhibit spatial movements relative to this stimulus. In rodents, behavioural light aversion (BLA is a well-documented but poorly understood phenomenon during which animals attribute salience to light and remove themselves from it. Here, using genetically modified mice and an open field behavioural paradigm, we investigate the role of melanopsin in BLA. While wildtype (WT, melanopsin knockout (Opn4(-/- and rd/rd cl (melanopsin only (MO mice all exhibit BLA, our novel methodology reveals that isolated melanopsin photoreception produces a slow, potentiating response to light. In order to control for the involvement of pupillary constriction in BLA we eliminated this variable with topical atropine application. This manipulation enhanced BLA in WT and MO mice, but most remarkably, revealed light aversion in triple knockout (TKO mice, lacking three elements deemed essential for conventional photoreception (Opn4(-/- Gnat1(-/- Cnga3(-/-. Using a number of complementary strategies, we determined this response to be generated at the level of the retina. Our findings have significant implications for the understanding of how melanopsin signalling may modulate aversive responses to light in mice and humans. In addition, we also reveal a clear potential for light perception in TKO mice.

What Controls Thermo-osmosis? Molecular Simulations Show the Critical Role of Interfacial Hydrodynamics

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Fu, Li; Merabia, Samy; Joly, Laurent

2017-11-01

Thermo-osmotic and related thermophoretic phenomena can be found in many situations from biology to colloid science, but the underlying molecular mechanisms remain largely unexplored. Using molecular dynamics simulations, we measure the thermo-osmosis coefficient by both mechanocaloric and thermo-osmotic routes, for different solid-liquid interfacial energies. The simulations reveal, in particular, the crucial role of nanoscale interfacial hydrodynamics. For nonwetting surfaces, thermo-osmotic transport is largely amplified by hydrodynamic slip at the interface. For wetting surfaces, the position of the hydrodynamic shear plane plays a key role in determining the amplitude and sign of the thermo-osmosis coefficient. Finally, we measure a giant thermo-osmotic response of the water-graphene interface, which we relate to the very low interfacial friction displayed by this system. These results open new perspectives for the design of efficient functional interfaces for, e.g., waste-heat harvesting.

What Controls Thermo-osmosis? Molecular Simulations Show the Critical Role of Interfacial Hydrodynamics.

Science.gov (United States)

Fu, Li; Merabia, Samy; Joly, Laurent

2017-11-24

Thermo-osmotic and related thermophoretic phenomena can be found in many situations from biology to colloid science, but the underlying molecular mechanisms remain largely unexplored. Using molecular dynamics simulations, we measure the thermo-osmosis coefficient by both mechanocaloric and thermo-osmotic routes, for different solid-liquid interfacial energies. The simulations reveal, in particular, the crucial role of nanoscale interfacial hydrodynamics. For nonwetting surfaces, thermo-osmotic transport is largely amplified by hydrodynamic slip at the interface. For wetting surfaces, the position of the hydrodynamic shear plane plays a key role in determining the amplitude and sign of the thermo-osmosis coefficient. Finally, we measure a giant thermo-osmotic response of the water-graphene interface, which we relate to the very low interfacial friction displayed by this system. These results open new perspectives for the design of efficient functional interfaces for, e.g., waste-heat harvesting.

Genetic Diversity of the Critically Endangered Thuja sutchuenensis Revealed by ISSR Markers and the Implications for Conservation

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Zeping Jiang

2013-07-01

Full Text Available Thuja sutchuenensis Franch. is a critically endangered plant endemic to the North-East Chongqing, China. Genetic variation was studied to assess the distribution of genetic diversity within and among seven populations from the single remnant locations, using inter-simple sequence repeat (ISSR markers. A total of 15 primers generated 310 well defined bands, with an average of 20.7 bands per primer. The seven populations revealed a relatively high level of genetic diversity in the species. The percentage of polymorphic bands, Nei’s gene diversity and Shannon’s information index at the population and species level were 76.1%, 0.155, 0.252 and 100%, 0.165, 0.295, respectively. A low level of genetic differentiation among populations (GST = 0.102, in line with the results of Analyses of Molecular Variance (AMOVA, and a high level of gene flow (Nm = 4.407 were observed. Both the Unweighted Pair Group Method with Arithmatic Mean (UPGMA cluster analysis and Principal Coordinates Analysis (PCoA supported the grouping of all seven populations into two groups. In addition, Mantel test revealed no significant correlation between genetic and geographical distances (r = 0.329, p = 0.100. The low genetic differentiation among populations implies that the conservation efforts should aim to preserve all the extant populations of this endangered species.

Critical success factors for implementing risk management systems in developing countries

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M.Reza Hosseini

2016-03-01

Full Text Available A review of published studies on risk management in developing countries reveals that critical success factors for implementing risk management has remained an under-researched area of investigation. This paper is aimed at investigating the perceptions of construction professionals concerning the critical success factors (CSFs for implementation of risk management systems (IRMS. Survey data was collected from 87 construction professionals from the Iranian construction industry as a developing country. The results indicate that four factors are regarded as highly critical: ‘support from managers’, ‘inclusion of risk management in construction education and training courses for construction practitioners’, ‘attempting to deliver projects systematically’, and ‘awareness and knowledge of the process for implementing risk management’. Assessing the associations among CSFs also highlighted the crucial role of enhancing the effectiveness of knowledge management practices in construction organisations. Study also revealed that parties involved in projects do not agree on the level of importance of CSFs for implementing risk management in developing countries. This study contributes to practice and research in several ways. For practice, it increases understanding of how closely knowledge management is associated with the implementation of risk management systems in developing countries. For research, the findings would encourage construction practitioners to support effective knowledge management as a precursor to higher levels of risk management implementation on construction projects.

Utilization of critical periods during development to study the effects of low levels of environmental agents

International Nuclear Information System (INIS)

Russell, L.B.

1981-01-01

This chapter shows how careful definition of critical periods in the development of selected characters can result in experimental systems that may be highly useful in studying risk at low levels of exposure. Presents 3 systems that utilize critical periods to study low-level effects: 1) cell kinetics as an indicator of nervous-system maldevelopment; 2) oocyte depletion; and 3) homeotic shifts in the skeleton. Discusses application of the sensitive systems to the testing of chemicals and the role of sensitive stages in estimating risk. Suggests that tests such as the 3 discussed in this paper, which are developed with strict attention to specific critical periods, can provide rapid and sensitive means for revealing whether an agent is capable of causing developmental interference. Concludes that epidemiological investigations can lose much of their value unless critical periods are known for the endpoints being studied

A Critical Analysis of the Conceptualisation of "Coaching Philosophy"

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Cushion, Christopher; Partington, Mark

2016-01-01

The aim of this paper was to critically review existing literature relating to, and critically analyse current conceptualisations of, "coaching philosophy." The review reveals a bewildering approach to definitions, terms and frameworks that have limited explanation and reveal a lack of conceptual clarity. It is argued that rather than…

The role of critical thinking skills and learning styles of university students in their academic performance

Directory of Open Access Journals (Sweden)

ZOHRE GHAZIVAKILI

2014-07-01

Full Text Available Introduction: The current world needs people who have a lot of different abilities such as cognition and application of different ways of thinking, research, problem solving, critical thinking skills and creativity. In addition to critical thinking, learning styles is another key factor which has an essential role in the process of problem solving. This study aimed to determine the relationship between learning styles and critical thinking of students and their academic performance in Alborz University of Medical Sciences. Methods: This cross-correlation study was performed in 2012, on 216 students of Alborz University who were selected randomly by the stratified method. The data was obtained via a three-part questionnaire included demographic data, Kolb standardized questionnaire of learning style and California critical thinking standardized questionnaire. The academic performance of the students was extracted by the school records. The validity of the instruments was determined in terms of content validity, and the reliability was gained through internal consistency methods. Cronbach's alpha coefficient was found to be 0.78 for the California critical thinking questionnaire. The Chi Square test, Independent T-test, one way ANOVA and Pearson Correlation test were used to determine relationship between variables. The Package SPSS14 statistical software was used to analyze data with a significant level of p<0.05. Results: Our findings indicated the significant difference of mean score in four learning style, suggesting university students with convergent learning style have better performance than other groups. Also learning style had a relationship with age, gender, field of study, semester and job. The results about the critical thinking of the students showed that the mean of deductive reasoning and evaluation skills were higher than that of other skills and analytical skills had the lowest mean and there was a positive significant

Border Cosmopolitanism in Critical Peace Education

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Golding, David

2017-01-01

This paper intends to contribute to recent developments in the theory of critical peace education. The role of cosmopolitanism in critical peace education is examined, particularly in relation to universal moral inclusion, secularism and universalism. It is then recommended that critical peace education draw from post-universalist and dialogical…

Nitric oxide and TNFα are critical regulators of reversible lymph node vascular remodeling and adaptive immune response.

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Stephanie L Sellers

Full Text Available Lymph node (LN vascular growth, at the level of the main arteriole, was recently characterized for the first time during infection. Arteriole diameter was shown to increase for at least seven days and to occur via a CD4(+ T cell dependent mechanism, with vascular expansion playing a critical role in regulating induction of adaptive immune response. Here, using intravital microscopy of the inguinal LN during herpes simplex type II (HSV-2 infection, the data provides the first studies that demonstrate arteriole expansion during infection is a reversible vascular event that occurs via eutrophic outward remodeling. Furthermore, using genetic ablation models, and pharmacological blockade, we reveal arteriole remodeling and LN hypertrophy to be dependent upon both endothelial nitric oxide synthase (eNOS and TNFα expression. Additionally, we reveal transient changes in nitric oxide (NO levels to be a notable feature of response to viral infection and LN vascular remodeling and provide evidence that mast cells are the critical source of TNFα required to drive arteriole remodeling. Overall, this study is the first to fully characterize LN arteriole vascular changes throughout the course of infection. It effectively reveals a novel role for NO and TNFα in LN cellularity and changes in LN vascularity, which represent key advances in understanding LN vascular physiology and adaptive immune response.

Why Critical design is useless

DEFF Research Database (Denmark)

Ebbesen, Toke Riis

Critical design is proliferating. According to Raby, this kind of design creates artefacts in order to “challenge narrow assumptions, preconceptions, and givens about the role products play in everyday life” (Raby, 2008, 94). Conceived basically as "useless", the value of critical design...

Unexpected inhibition of CO₂ gas hydrate formation in dilute TBAB solutions and the critical role of interfacial water structure

Energy Technology Data Exchange (ETDEWEB)

Nguyen, Ngoc N.; Nguyen, Anh V.; Nguyen, Khoi T.; Rintoul, Llew; Dang, Liem X.

2016-12-01

Gas hydrates formed under moderated conditions open up novel approaches to tackling issues related to energy supply, gas separation, and CO₂ sequestration. Several additives like tetra-n-butylammonium bromide (TBAB) have been empirically developed and used to promote gas hydrate formation. Here we report unexpected experimental results which show that TBAB inhibits CO₂ gas hydrate formation when used at minuscule concentration. We also used spectroscopic techniques and molecular dynamics simulation to gain further insights and explain the experimental results. They have revealed the critical role of water alignment at the gas-water interface induced by surface adsorption of tetra-n-butylammonium cation (TBA⁺) which gives rise to the unexpected inhibition of dilute TBAB solution. The water perturbation by TBA⁺ in the bulk is attributed to the promotion effect of high TBAB concentration on gas hydrate formation. We explain our finding using the concept of activation energy of gas hydrate formation. Our results provide a step toward to mastering the control of gas hydrate formation.

Mediating role of critical thinking disposition in the relationship between perceived barriers to research use and evidence-based practice.

Science.gov (United States)

Kim, Sun-Ae; Song, Youngshin; Sim, Hee-Sook; Ahn, Eun-Kyong; Kim, Jung-Hee

2015-01-01

Despite the importance of critical thinking in clinical and educational settings, little is known about its role in evidence-based practice (EBP). This study examined whether critical thinking disposition (CTD) mediates the relationship between perceived barriers to research use and EBP in clinical nurses (N=409). A path diagram using structural equation modeling was used to estimate the direct and indirect effects of perceived barriers to research use on EBP, controlling for CTD as a mediator. CTD partially mediated the relationship between perceived barriers to research use and EBP. Furthermore, the hypothesized mediation model demonstrated an appropriate fit to the data. Individual and organizational efforts are needed to help nurses further improve their critical thinking skills. CTD is important as research barriers to engage effectively in EBP. Without the skills to evaluate evidence carefully, research utilization may be compromised.

Structures of the first representatives of Pfam family PF06684 (DUF1185) reveal a novel variant of the Bacillus chorismate mutase fold and suggest a role in amino-acid metabolism

International Nuclear Information System (INIS)

Bakolitsa, Constantina; Kumar, Abhinav; Jin, Kevin K.; McMullan, Daniel; Krishna, S. Sri; Miller, Mitchell D.; Abdubek, Polat; Acosta, Claire; Astakhova, Tamara; Axelrod, Herbert L.; Burra, Prasad; Carlton, Dennis; Chen, Connie; Chiu, Hsiu-Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C.; Duan, Lian; Elias, Ylva; Ellrott, Kyle; Ernst, Dustin; Farr, Carol L.; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Grzechnik, Slawomir K.; Han, Gye Won; Jaroszewski, Lukasz; Johnson, Hope A.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Marciano, David; Morse, Andrew T.; Murphy, Kevin D.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Paulsen, Jessica; Puckett, Christina; Reyes, Ron; Rife, Christopher L.; Sefcovic, Natasha; Tien, Henry J.; Trame, Christine B.; Trout, Christina V.; Bedem, Henry van den; Weekes, Dana; White, Aprilfawn; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-Andre; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

2010-01-01

Structures of the first representatives of PF06684 (DUF1185) reveal a Bacillus chorismate mutase-like fold with a potential role in amino-acid synthesis. The crystal structures of BB2672 and SPO0826 were determined to resolutions of 1.7 and 2.1 Å by single-wavelength anomalous dispersion and multiple-wavelength anomalous dispersion, respectively, using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). These proteins are the first structural representatives of the PF06684 (DUF1185) Pfam family. Structural analysis revealed that both structures adopt a variant of the Bacillus chorismate mutase fold (BCM). The biological unit of both proteins is a hexamer and analysis of homologs indicates that the oligomer interface residues are highly conserved. The conformation of the critical regions for oligomerization appears to be dependent on pH or salt concentration, suggesting that this protein might be subject to environmental regulation. Structural similarities to BCM and genome-context analysis suggest a function in amino-acid synthesis

Teaching Sociology and Womens’ Critical Thinking

OpenAIRE

Mohammad-Ali Zaki

2013-01-01

Introduction Sociology of Teaching sociology is seen as a fresh new place to explore the importance and role of critical thinking in the sociology of education has been one of the most important issues to consider.Principles of Sociology course ample opportunities for students to develop critical thinking skills and attitudes and serves as a missionary spirit, critical thinking has suggested an alternative,Areas has brought the development of critical thinking. Learn the basics of critical...

Intensive care survivors' experiences of ward-based care: Meleis' theory of nursing transitions and role development among critical care outreach services.

Science.gov (United States)

Ramsay, Pam; Huby, Guro; Thompson, Andrew; Walsh, Tim

2014-03-01

To explore the psychosocial needs of patients discharged from intensive care, the extent to which they are captured using existing theory on transitions in care and the potential role development of critical care outreach, follow-up and liaison services. Intensive care patients are at an increased risk of adverse events, deterioration or death following ward transfer. Nurse-led critical care outreach, follow-up or liaison services have been adopted internationally to prevent these potentially avoidable sequelae. The need to provide patients with psychosocial support during the transition to ward-based care has also been identified, but the evidence base for role development is currently limited. Twenty participants were invited to discuss their experiences of ward-based care as part of a broader study on recovery following prolonged critical illness. Psychosocial distress was a prominent feature of their accounts, prompting secondary data analysis using Meleis et al.'s mid-range theory on experiencing transitions. Participants described a sense of disconnection in relation to profound debilitation and dependency and were often distressed by a perceived lack of understanding, indifference or insensitivity among ward staff to their basic care needs. Negotiating the transition between dependence and independence was identified as a significant source of distress following ward transfer. Participants varied in the extent to which they were able to express their needs and negotiate recovery within professionally mediated boundaries. These data provide new insights into the putative origins of the psychosocial distress that patients experience following ward transfer. Meleis et al.'s work has resonance in terms of explicating intensive care patients' experiences of psychosocial distress throughout the transition to general ward-based care, such that the future role development of critical care outreach, follow-up and liaison services may be more theoretically informed

A Critical Role for CD200R Signaling in Limiting the Growth and Metastasis of CD200+ Melanoma.

Science.gov (United States)

Liu, Jin-Qing; Talebian, Fatemeh; Wu, Lisha; Liu, Zhihao; Li, Ming-Song; Wu, Laichu; Zhu, Jianmin; Markowitz, Joseph; Carson, William E; Basu, Sujit; Bai, Xue-Feng

2016-08-15

CD200 is a cell surface glycoprotein that functions through engaging CD200R on cells of the myeloid lineage and inhibits their functions. Expression of CD200 was implicated in a variety of human cancer cells, including melanoma cells; however, its roles in tumor growth and immunity are not clearly understood. In this study, we used CD200R-deficient mice and the B16 tumor model to evaluate this issue. We found that CD200R-deficient mice exhibited accelerated growth of CD200(+), but not CD200(-), B16 tumors. Strikingly, CD200R-deficient mice receiving CD200(+) B16 cells i.v. exhibited massive tumor growth in multiple organs, including liver, lung, kidney, and peritoneal cavity, whereas the growth of the same tumors in wild-type mice was limited. CD200(+) tumors grown in CD200R-deficient mice contained higher numbers of CD11b(+)Ly6C(+) myeloid cells, exhibited increased expression of VEGF and HIF1α genes with increased angiogenesis, and showed significantly reduced infiltration of CD4(+) and CD8(+) T cells, presumably as the result of reduced expression of T cell chemokines, such as CXCL9 and CXCL16. The liver from CD200R-deficient mice, under metastatic growth of CD200(+) tumors, contained significantly increased numbers of CD11b(+)Gr1(-) myeloid cells and Foxp3(+) regulatory T cells and reduced numbers of NK cells. Liver T cells also had a reduced capacity to produce IFN-γ or TNF-α. Taken together, we revealed a critical role for CD200R signaling in limiting the growth and metastasis of CD200(+) tumors. Thus, targeting CD200R signaling may potentially interfere with the metastatic growth of CD200(+) tumors, like melanoma. Copyright © 2016 by The American Association of Immunologists, Inc.

Genome-wide characterization of the WRKY gene family in radish (Raphanus sativus L.) reveals its critical functions under different abiotic stresses.

Science.gov (United States)

Karanja, Bernard Kinuthia; Fan, Lianxue; Xu, Liang; Wang, Yan; Zhu, Xianwen; Tang, Mingjia; Wang, Ronghua; Zhang, Fei; Muleke, Everlyne M'mbone; Liu, Liwang

2017-11-01

The radish WRKY gene family was genome-widely identified and played critical roles in response to multiple abiotic stresses. The WRKY is among the largest transcription factors (TFs) associated with multiple biological activities for plant survival, including control response mechanisms against abiotic stresses such as heat, salinity, and heavy metals. Radish is an important root vegetable crop and therefore characterization and expression pattern investigation of WRKY transcription factors in radish is imperative. In the present study, 126 putative WRKY genes were retrieved from radish genome database. Protein sequence and annotation scrutiny confirmed that RsWRKY proteins possessed highly conserved domains and zinc finger motif. Based on phylogenetic analysis results, RsWRKYs candidate genes were divided into three groups (Group I, II and III) with the number 31, 74, and 20, respectively. Additionally, gene structure analysis revealed that intron-exon patterns of the WRKY genes are highly conserved in radish. Linkage map analysis indicated that RsWRKY genes were distributed with varying densities over nine linkage groups. Further, RT-qPCR analysis illustrated the significant variation of 36 RsWRKY genes under one or more abiotic stress treatments, implicating that they might be stress-responsive genes. In total, 126 WRKY TFs were identified from the R. sativus genome wherein, 35 of them showed abiotic stress-induced expression patterns. These results provide a genome-wide characterization of RsWRKY TFs and baseline for further functional dissection and molecular evolution investigation, specifically for improving abiotic stress resistances with an ultimate goal of increasing yield and quality of radish.

Critical role of types 2 and 3 deiodinases in the negative regulation of gene expression by T₃in the mouse cerebral cortex.

Science.gov (United States)

Hernandez, Arturo; Morte, Beatriz; Belinchón, Mónica M; Ceballos, Ainhoa; Bernal, Juan

2012-06-01

Thyroid hormones regulate brain development and function through the control of gene expression, mediated by binding of T(3) to nuclear receptors. Brain T(3) concentration is tightly controlled by homeostatic mechanisms regulating transport and metabolism of T(4) and T(3). We have examined the role of the inactivating enzyme type 3 deiodinase (D3) in the regulation of 43 thyroid hormone-dependent genes in the cerebral cortex of 30-d-old mice. D3 inactivation increased slightly the expression of two of 22 positively regulated genes and significantly decreased the expression of seven of 21 negatively regulated genes. Administration of high doses of T(3) led to significant changes in the expression of 12 positive genes and three negative genes in wild-type mice. The response to T(3) treatment was enhanced in D3-deficient mice, both in the number of genes and in the amplitude of the response, demonstrating the role of D3 in modulating T(3) action. Comparison of the effects on gene expression observed in D3 deficiency with those in hypothyroidism, hyperthyroidism, and type 2 deiodinase (D2) deficiency revealed that the negative genes are more sensitive to D2 and D3 deficiencies than the positive genes. This observation indicates that, in normal physiological conditions, D2 and D3 play critical roles in maintaining local T(3) concentrations within a very narrow range. It also suggests that negatively and positively regulated genes do not have the same physiological significance or that their regulation by thyroid hormone obeys different paradigms at the molecular or cellular levels.

Quantitative Proteomics of the Tonoplast Reveals a Role for Glycolytic Enzymes in Salt Tolerance[C][W

Science.gov (United States)

Barkla, Bronwyn J.; Vera-Estrella, Rosario; Hernández-Coronado, Marcela; Pantoja, Omar

2009-01-01

To examine the role of the tonoplast in plant salt tolerance and identify proteins involved in the regulation of transporters for vacuolar Na+ sequestration, we exploited a targeted quantitative proteomics approach. Two-dimensional differential in-gel electrophoresis analysis of free flow zonal electrophoresis separated tonoplast fractions from control, and salt-treated Mesembryanthemum crystallinum plants revealed the membrane association of glycolytic enzymes aldolase and enolase, along with subunits of the vacuolar H+-ATPase V-ATPase. Protein blot analysis confirmed coordinated salt regulation of these proteins, and chaotrope treatment indicated a strong tonoplast association. Reciprocal coimmunoprecipitation studies revealed that the glycolytic enzymes interacted with the V-ATPase subunit B VHA-B, and aldolase was shown to stimulate V-ATPase activity in vitro by increasing the affinity for ATP. To investigate a physiological role for this association, the Arabidopsis thaliana cytoplasmic enolase mutant, los2, was characterized. These plants were salt sensitive, and there was a specific reduction in enolase abundance in the tonoplast from salt-treated plants. Moreover, tonoplast isolated from mutant plants showed an impaired ability for aldolase stimulation of V-ATPase hydrolytic activity. The association of glycolytic proteins with the tonoplast may not only channel ATP to the V-ATPase, but also directly upregulate H+-pump activity. PMID:20028841

The role of minimum supply and social vulnerability assessment for governing critical infrastructure failure: current gaps and future agenda

Directory of Open Access Journals (Sweden)

M. Garschagen

2018-04-01

Full Text Available Increased attention has lately been given to the resilience of critical infrastructure in the context of natural hazards and disasters. The major focus therein is on the sensitivity of critical infrastructure technologies and their management contingencies. However, strikingly little attention has been given to assessing and mitigating social vulnerabilities towards the failure of critical infrastructure and to the development, design and implementation of minimum supply standards in situations of major infrastructure failure. Addressing this gap and contributing to a more integrative perspective on critical infrastructure resilience is the objective of this paper. It asks which role social vulnerability assessments and minimum supply considerations can, should and do – or do not – play for the management and governance of critical infrastructure failure. In its first part, the paper provides a structured review on achievements and remaining gaps in the management of critical infrastructure and the understanding of social vulnerabilities towards disaster-related infrastructure failures. Special attention is given to the current state of minimum supply concepts with a regional focus on policies in Germany and the EU. In its second part, the paper then responds to the identified gaps by developing a heuristic model on the linkages of critical infrastructure management, social vulnerability and minimum supply. This framework helps to inform a vision of a future research agenda, which is presented in the paper's third part. Overall, the analysis suggests that the assessment of socially differentiated vulnerabilities towards critical infrastructure failure needs to be undertaken more stringently to inform the scientifically and politically difficult debate about minimum supply standards and the shared responsibilities for securing them.

The role of minimum supply and social vulnerability assessment for governing critical infrastructure failure: current gaps and future agenda

Science.gov (United States)

Garschagen, Matthias; Sandholz, Simone

2018-04-01

Increased attention has lately been given to the resilience of critical infrastructure in the context of natural hazards and disasters. The major focus therein is on the sensitivity of critical infrastructure technologies and their management contingencies. However, strikingly little attention has been given to assessing and mitigating social vulnerabilities towards the failure of critical infrastructure and to the development, design and implementation of minimum supply standards in situations of major infrastructure failure. Addressing this gap and contributing to a more integrative perspective on critical infrastructure resilience is the objective of this paper. It asks which role social vulnerability assessments and minimum supply considerations can, should and do - or do not - play for the management and governance of critical infrastructure failure. In its first part, the paper provides a structured review on achievements and remaining gaps in the management of critical infrastructure and the understanding of social vulnerabilities towards disaster-related infrastructure failures. Special attention is given to the current state of minimum supply concepts with a regional focus on policies in Germany and the EU. In its second part, the paper then responds to the identified gaps by developing a heuristic model on the linkages of critical infrastructure management, social vulnerability and minimum supply. This framework helps to inform a vision of a future research agenda, which is presented in the paper's third part. Overall, the analysis suggests that the assessment of socially differentiated vulnerabilities towards critical infrastructure failure needs to be undertaken more stringently to inform the scientifically and politically difficult debate about minimum supply standards and the shared responsibilities for securing them.

Taking Critical Ontology Seriously

DEFF Research Database (Denmark)

Wigger, Angela; Horn, Laura

2017-01-01

To be ‘critical’ has become fashionable among social scientists in various disciplines. Only a few decades ago, the prefix ‘critical’ was almost automatically associated with Western Marxism and in particular the Frankfurt School. Today, the term critical is no longer limited to a single...... theoretical approach, but pertains to a vast range of approaches, including feminist, reflexive, postcolonial, postmodern or poststructuralist studies, and studies committed to a post-positivist epistemology more generally. But what does critical social science actually mean? Which implications does critical...... a primer on a few core dimensions of critical social science and its central premises. It discusses first what critical social science is not, and clarifies key differences between what is commonly referred to as ‘mainstream’ and ‘critical’ social science perspectives. It addresses the role of normative...

Hmong Parents Critical Reflections on Their Childrens Heritage Language Maintenance

Directory of Open Access Journals (Sweden)

Terry Yang

2008-01-01

Full Text Available This study utilizes a qualitative method to explore the critical reflections of Hmong parents helping their children maintain their native language. Specifically, it examines parents thoughts, feelings and experiences related to Hmong language maintenance. Findings reveal that Hmong parents worry about their children losing their ability to speak their native language. They believe that maintaining the Hmong language provides advantages in achieving academic success, attaining careers, and continuing to serve as role models in the community. Parents stressed the need to use Hmong at home in order to help their children develop and maintain the language. They reported some successes in doing so, while acknowledging several challenges.

Botrytis cinerea protein O-mannosyltransferases play critical roles in morphogenesis, growth, and virulence.

Directory of Open Access Journals (Sweden)

Mario González

Full Text Available Protein O-glycosylation is crucial in determining the structure and function of numerous secreted and membrane-bound proteins. In fungi, this process begins with the addition of a mannose residue by protein O-mannosyltransferases (PMTs in the lumen side of the ER membrane. We have generated mutants of the three Botrytis cinerea pmt genes to study their role in the virulence of this wide-range plant pathogen. B. cinerea PMTs, especially PMT2, are critical for the stability of the cell wall and are necessary for sporulation and for the generation of the extracellular matrix. PMTs are also individually required for full virulence in a variety of hosts, with a special role in the penetration of intact plant leaves. The most significant case is that of grapevine leaves, whose penetration requires the three functional PMTs. Furthermore, PMT2 also contributes significantly to fungal adherence on grapevine and tobacco leaves. Analysis of extracellular and membrane proteins showed significant changes in the pattern of protein secretion and glycosylation by the pmt mutants, and allowed the identification of new protein substrates putatively glycosylated by specific PMTs. Since plants do no possess these enzymes, PMTs constitute a promising target in the development of novel control strategies against B. cinerea.

Neutrophils in critical illness.

Science.gov (United States)

McDonald, Braedon

2018-03-01

During critical illness, dramatic alterations in neutrophil biology are observed including abnormalities of granulopoeisis and lifespan, cell trafficking and antimicrobial effector functions. As a result, neutrophils transition from powerful antimicrobial protectors into dangerous mediators of tissue injury and organ dysfunction. In this article, the role of neutrophils in the pathogenesis of critical illness (sepsis, trauma, burns and others) will be explored, including pathological changes to neutrophil function during critical illness and the utility of monitoring aspects of the neutrophil phenotype as biomarkers for diagnosis and prognostication. Lastly, we review findings from clinical trials of therapies that target the harmful effects of neutrophils, providing a bench-to-bedside perspective on neutrophils in critical illness.

SWATH label-free proteomics analyses revealed the roles of oxidative stress and antioxidant defensing system in sclerotia formation of Polyporus umbellatus

Science.gov (United States)

Li, Bing; Tian, Xiaofang; Wang, Chunlan; Zeng, Xu; Xing, Yongmei; Ling, Hong; Yin, Wanqiang; Tian, Lixia; Meng, Zhixia; Zhang, Jihui; Guo, Shunxing

2017-01-01

Understanding the initiation and maturing mechanisms is important for rational manipulating sclerotia differentiation and growth from hypha of Polyporus umbellatus. Proteomes in P. umbellatus sclerotia and hyphae at initial, developmental and mature phases were studied. 1391 proteins were identified by nano-liquid chromatograph-mass spectrometry (LC-MS) in Data Dependant Acquisition mode, and 1234 proteins were quantified successfully by Sequential Window Acquisition of all THeoretical fragment ion spectra-MS (SWATH-MS) technology. There were 347 differentially expressed proteins (DEPs) in sclerotia at initial phase compared with those in hypha, and the DEP profiles were dynamically changing with sclerotia growth. Oxidative stress (OS) in sclerotia at initial phase was indicated by the repressed proteins of respiratory chain, tricarboxylic acid cycle and the activation of glycolysis/gluconeogenesis pathways were determined based on DEPs. The impact of glycolysis/gluconeogenesis on sclerotium induction was further verified by glycerol addition assays, in which 5% glycerol significantly increased sclerotial differentiation rate and biomass. It can be speculated that OS played essential roles in triggering sclerotia differentiation from hypha of P. umbellatus, whereas antioxidant activity associated with glycolysis is critical for sclerotia growth. These findings reveal a mechanism for sclerotial differentiation in P. umbellatus, which may also be applicable for other fungi.

Switch of Sensitivity Dynamics Revealed with DyGloSA Toolbox for Dynamical Global Sensitivity Analysis as an Early Warning for System's Critical Transition

Science.gov (United States)

Baumuratova, Tatiana; Dobre, Simona; Bastogne, Thierry; Sauter, Thomas

2013-01-01

Systems with bifurcations may experience abrupt irreversible and often unwanted shifts in their performance, called critical transitions. For many systems like climate, economy, ecosystems it is highly desirable to identify indicators serving as early warnings of such regime shifts. Several statistical measures were recently proposed as early warnings of critical transitions including increased variance, autocorrelation and skewness of experimental or model-generated data. The lack of automatized tool for model-based prediction of critical transitions led to designing DyGloSA – a MATLAB toolbox for dynamical global parameter sensitivity analysis (GPSA) of ordinary differential equations models. We suggest that the switch in dynamics of parameter sensitivities revealed by our toolbox is an early warning that a system is approaching a critical transition. We illustrate the efficiency of our toolbox by analyzing several models with bifurcations and predicting the time periods when systems can still avoid going to a critical transition by manipulating certain parameter values, which is not detectable with the existing SA techniques. DyGloSA is based on the SBToolbox2 and contains functions, which compute dynamically the global sensitivity indices of the system by applying four main GPSA methods: eFAST, Sobol's ANOVA, PRCC and WALS. It includes parallelized versions of the functions enabling significant reduction of the computational time (up to 12 times). DyGloSA is freely available as a set of MATLAB scripts at http://bio.uni.lu/systems_biology/software/dyglosa. It requires installation of MATLAB (versions R2008b or later) and the Systems Biology Toolbox2 available at www.sbtoolbox2.org. DyGloSA can be run on Windows and Linux systems, -32 and -64 bits. PMID:24367574

Switch of sensitivity dynamics revealed with DyGloSA toolbox for dynamical global sensitivity analysis as an early warning for system's critical transition.

Science.gov (United States)

Baumuratova, Tatiana; Dobre, Simona; Bastogne, Thierry; Sauter, Thomas

2013-01-01

Systems with bifurcations may experience abrupt irreversible and often unwanted shifts in their performance, called critical transitions. For many systems like climate, economy, ecosystems it is highly desirable to identify indicators serving as early warnings of such regime shifts. Several statistical measures were recently proposed as early warnings of critical transitions including increased variance, autocorrelation and skewness of experimental or model-generated data. The lack of automatized tool for model-based prediction of critical transitions led to designing DyGloSA - a MATLAB toolbox for dynamical global parameter sensitivity analysis (GPSA) of ordinary differential equations models. We suggest that the switch in dynamics of parameter sensitivities revealed by our toolbox is an early warning that a system is approaching a critical transition. We illustrate the efficiency of our toolbox by analyzing several models with bifurcations and predicting the time periods when systems can still avoid going to a critical transition by manipulating certain parameter values, which is not detectable with the existing SA techniques. DyGloSA is based on the SBToolbox2 and contains functions, which compute dynamically the global sensitivity indices of the system by applying four main GPSA methods: eFAST, Sobol's ANOVA, PRCC and WALS. It includes parallelized versions of the functions enabling significant reduction of the computational time (up to 12 times). DyGloSA is freely available as a set of MATLAB scripts at http://bio.uni.lu/systems_biology/software/dyglosa. It requires installation of MATLAB (versions R2008b or later) and the Systems Biology Toolbox2 available at www.sbtoolbox2.org. DyGloSA can be run on Windows and Linux systems, -32 and -64 bits.

Red blood cells in hemorrhagic shock: a critical role for glutaminolysis in fueling alanine transamination in rats.

Science.gov (United States)

Reisz, Julie A; Slaughter, Anne L; Culp-Hill, Rachel; Moore, Ernest E; Silliman, Christopher C; Fragoso, Miguel; Peltz, Erik D; Hansen, Kirk C; Banerjee, Anirban; D'Alessandro, Angelo

2017-07-25

Red blood cells (RBCs) are the most abundant host cell in the human body and play a critical role in oxygen transport and systemic metabolic homeostasis. Hypoxic metabolic reprogramming of RBCs in response to high-altitude hypoxia or anaerobic storage in the blood bank has been extensively described. However, little is known about the RBC metabolism following hemorrhagic shock (HS), the most common preventable cause of death in trauma, the global leading cause of total life-years lost. Metabolomics analyses were performed through ultra-high pressure liquid chromatography-mass spectrometry on RBCs from Sprague-Dawley rats undergoing HS (mean arterial pressure [MAP], 80 mm Hg). Steady-state measurements were accompanied by metabolic flux analysis upon tracing of in vivo-injected 13 C 15 N-glutamine or inhibition of glutaminolysis using the anticancer drug CB-839. RBC metabolic phenotypes recapitulated the systemic metabolic reprogramming observed in plasma from the same rodent model. Results indicate that shock RBCs rely on glutamine to fuel glutathione (GSH) synthesis and pyruvate transamination, whereas abrogation of glutaminolysis conferred early mortality and exacerbated lactic acidosis and systemic accumulation of succinate, a predictor of mortality in the military and civilian critically ill populations. Glutamine is here identified as an essential amine group donor in HS RBCs, plasma, liver, and lungs, providing additional rationale for the central role glutaminolysis plays in metabolic reprogramming and survival following severe hemorrhage.

Critical role of neuropeptides B/W receptor 1 signaling in social behavior and fear memory.

Directory of Open Access Journals (Sweden)

Ruby Nagata-Kuroiwa

Full Text Available Neuropeptide B/W receptor 1 (NPBWR1 is a G-protein coupled receptor, which was initially reported as an orphan receptor, and whose ligands were identified by this and other groups in 2002 and 2003. To examine the physiological roles of NPBWR1, we examined phenotype of Npbwr1⁻/⁻ mice. When presented with an intruder mouse, Npbwr1⁻/⁻ mice showed impulsive contact with the strange mice, produced more intense approaches toward them, and had longer contact and chasing time along with greater and sustained elevation of heart rate and blood pressure compared to wild type mice. Npbwr1⁻/⁻ mice also showed increased autonomic and neuroendocrine responses to physical stress, suggesting that impairment of NPBWR1 leads to stress vulnerability. We also observed that these mice show abnormality in the contextual fear conditioning test. These data suggest that NPBWR1 plays a critical role in limbic system function and stress responses. Histological and electrophysiological studies showed that NPBWR1 acts as an inhibitory regulator on a subpopulation of GABAergic neurons in the lateral division of the CeA and terminates stress responses. These findings suggest important roles of NPBWR1 in regulating amygdala function during physical and social stress.

Toward critical bioethics.

Science.gov (United States)

Árnason, Vilhjálmur

2015-04-01

This article deals with the question as to what makes bioethics a critical discipline. It considers different senses of criticism and evaluates their strengths and weaknesses. A primary method in bioethics as a philosophical discipline is critical thinking, which implies critical evaluation of concepts, positions, and arguments. It is argued that the type of analytical criticism that restricts its critical role to critical thinking of this type often suffers from other intellectual flaws. Three examples are taken to demonstrate this: premature criticism, uncritical self-understanding of theoretical assumptions, and narrow framing of bioethical issues. Such flaws can lead both to unfair treatment of authors and to uncritical discussion of topics. In this context, the article makes use of Häyry's analysis of different rationalities in bioethical approaches and argues for the need to recognize the importance of communicative rationality for critical bioethics. A radically different critical approach in bioethics, rooted in social theory, focuses on analyses of power relations neglected in mainstream critical thinking. It is argued that, although this kind of criticism provides an important alternative in bioethics, it suffers from other shortcomings that are rooted in a lack of normative dimensions. In order to complement these approaches and counter their shortcomings, there is a need for a bioethics enlightened by critical hermeneutics. Such hermeneutic bioethics is aware of its own assumptions, places the issues in a wide context, and reflects critically on the power relations that stand in the way of understanding them. Moreover, such an approach is dialogical, which provides both a critical exercise of speech and a normative dimension implied in the free exchange of reasons and arguments. This discussion is framed by Hedgecoe's argument that critical bioethics needs four elements: to be empirically rooted, theory challenging, reflexive, and politely skeptical.

Huntingtin-Interacting Protein 1-Related Protein Plays a Critical Role in Dendritic Development and Excitatory Synapse Formation in Hippocampal Neurons

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Lin Peng

2017-06-01

Full Text Available Huntingtin-interacting protein 1-related (HIP1R protein is considered to be an endocytic adaptor protein like the other two members of the Sla2 family, Sla2p and HIP1. They all contain homology domains responsible for the binding of clathrin, inositol lipids and F-actin. Previous studies have revealed that HIP1R is highly expressed in different regions of the mouse brain and localizes at synaptic structures. However, the function of HIP1R in the nervous system remains unknown. In this study, we investigated HIP1R function in cultured rat hippocampal neurons using an shRNA knockdown approach. We found that, after HIP1R knockdown, the dynamics and density of dendritic filopodia, and dendritic branching and complexity were significantly reduced in developing neurons, as well as the densities of dendritic spines and PSD95 clusters in mature neurons. Moreover, HIP1R deficiency led to significantly reduced expression of the ionotropic glutamate receptor GluA1, GluN2A and GluN2B subunits, but not the GABAA receptor α1 subunit. Similarly, HIP1R knockdown reduced the amplitude and frequency of the miniature excitatory postsynaptic current, but not of the miniature inhibitory postsynaptic current. In addition, the C-terminal proline-rich region of HIP1R responsible for cortactin binding was found to confer a dominant-negative effect on dendritic branching in cultured developing neurons, implying a critical role of cortactin binding in HIP1R function. Taken together, the results of our study suggest that HIP1R plays important roles in dendritic development and excitatory synapse formation and function.

The Lauramann Howe Russell Papers: a Window into Critical Care Medicine during the American Civil War.

Science.gov (United States)

Gorbaty, Benjamin

2017-10-01

The Civil War influenced all aspects of American society and culture, including the field of medicine and critical care. Union physician Lauramann Howe Russell's letter to his daughter, Ellen Howe, written on October 19, 1862, illustrates the changes in hospital construction, gender roles in healthcare and medical treatments which revolutionized healthcare during the Civil War. This letter offers a glimpse of the medical care of wounded soldiers during the early years of the Civil War. In describing his conversion hospital, he reveals the precursor to the new hospital construction which would greatly influence hospital design for decades to come. His description of women volunteers hints at the evolving role and growing importance of women in healthcare. Finally, the advancements in surgical and medical practice which developed during the Civil War are embodied in Russell's descriptions of his patients. His letter freezes a moment in medical history, bridging the gap between archaic medical practice and modern critical care. Copyright © 2017 Elsevier Inc. All rights reserved.

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

Directory of Open Access Journals (Sweden)

David Judah

Full Text Available Integrin-linked kinase (ILK is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

Multiple roles of integrin-linked kinase in epidermal development, maturation and pigmentation revealed by molecular profiling.

Science.gov (United States)

Judah, David; Rudkouskaya, Alena; Wilson, Ryan; Carter, David E; Dagnino, Lina

2012-01-01

Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function.

Canine Distemper Virus Fusion Activation: Critical Role of Residue E123 of CD150/SLAM.

Science.gov (United States)

Khosravi, Mojtaba; Bringolf, Fanny; Röthlisberger, Silvan; Bieringer, Maria; Schneider-Schaulies, Jürgen; Zurbriggen, Andreas; Origgi, Francesco; Plattet, Philippe

2016-02-01

Measles virus (MeV) and canine distemper virus (CDV) possess tetrameric attachment proteins (H) and trimeric fusion proteins, which cooperate with either SLAM or nectin 4 receptors to trigger membrane fusion for cell entry. While the MeV H-SLAM cocrystal structure revealed the binding interface, two distinct oligomeric H assemblies were also determined. In one of the conformations, two SLAM units were sandwiched between two discrete H head domains, thus spotlighting two binding interfaces ("front" and "back"). Here, we investigated the functional relevance of both interfaces in activating the CDV membrane fusion machinery. While alanine-scanning mutagenesis identified five critical regulatory residues in the front H-binding site of SLAM, the replacement of a conserved glutamate residue (E at position 123, replaced with A [E123A]) led to the most pronounced impact on fusion promotion. Intriguingly, while determination of the interaction of H with the receptor using soluble constructs revealed reduced binding for the identified SLAM mutants, no effect was recorded when physical interaction was investigated with the full-length counterparts of both molecules. Conversely, although mutagenesis of three strategically selected residues within the back H-binding site of SLAM did not substantially affect fusion triggering, nevertheless, the mutants weakened the H-SLAM interaction recorded with the membrane-anchored protein constructs. Collectively, our findings support a mode of binding between the attachment protein and the V domain of SLAM that is common to all morbilliviruses and suggest a major role of the SLAM residue E123, located at the front H-binding site, in triggering the fusion machinery. However, our data additionally support the hypothesis that other microdomain(s) of both glycoproteins (including the back H-binding site) might be required to achieve fully productive H-SLAM interactions. A complete understanding of the measles virus and canine distemper virus

Present knowledge and perspectives on the role of copper in brake materials and related environmental issues: A critical assessment

International Nuclear Information System (INIS)

Straffelini, Giovanni; Ciudin, Rodica; Ciotti, Alessandro; Gialanella, Stefano

2015-01-01

This critical review presents several aspects related to the use of copper as a main component in brake pads in road vehicles. The compositions of these materials are attracting increasing interest and concern due to the relative contribution of wear products to particulate matter emissions in the environment as a result of braking action even though there has been a reduction in exhaust products from internal combustion engines. We review the data on the main wear mechanisms in brake systems and highlight the positive role of copper. However, similar to other heavy metal emissions, even the release of copper into the atmosphere may have important environmental and health effects. Thus, several replacement strategies are being pursued, and the positive and negative features will be critically reviewed. Additionally, the future perspectives in materials development will be discussed. - Highlights: • Copper in brake pad materials: role and concerns. • Environmental and health impact of copper. • Copper replacement in frictional brake materials. • International legislation and standards on the above issues. - Importance of copper in brake pad materials and concern as regards environmental and health impact of its emission as brake wear product.

The critical interface

DEFF Research Database (Denmark)

Pold, Søren

2005-01-01

In this paper, I argue that aesthetics might serve the role of critical reflection on representation within the field of computing, and I demonstrate through three analytic examples from computer art how this might look like and what the contribution might be....

The Role of the Transcriptional Response to DNA Replication Stress.

Science.gov (United States)

Herlihy, Anna E; de Bruin, Robertus A M

2017-03-02

During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage.

The Role of the Transcriptional Response to DNA Replication Stress

Science.gov (United States)

Herlihy, Anna E.; de Bruin, Robertus A.M.

2017-01-01

During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage. PMID:28257104

Critical role of nucleotide-binding oligomerization domain-like receptor 3 in vascular repair

International Nuclear Information System (INIS)

Schlaweck, Sebastian; Zimmer, Sebastian; Struck, Rafael; Bartok, Eva; Werner, Nikos; Bauernfeind, Franz; Latz, Eicke; Nickenig, Georg; Hornung, Veit; Ghanem, Alexander

2011-01-01

Highlights: → NLRP3 is not required for systemic cardiovascular function in healthy mice. → NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and that it does not alter peripheral differential blood counts. → NLRP3 is critical in neointima formation following vascular injury. -- Abstract: Vascular remodeling characterized by hyperproliferative neointima formation is an unfavorable repair process that is triggered by vascular damage. This process is characterized by an increased local inflammatory and proliferative response that critically involves the pro-inflammatory cytokine interleukin-1β (IL-1β). IL-1β is expressed and cytosolically retained as a procytokine that requires additional processing prior to exerting its pro-inflammatory function. Maturation and release of pro IL-1β is governed by a cytosolic protein scaffold that is known as the inflammasome. Here we show that NLRP3 (NOD-like receptor family, pryin domain containing 3), an important activating component of the inflammasome, is involved in neointima formation after vascular injury. NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and does not alter peripheral differential blood counts. However, neointima development following wire injury of the carotid artery was significantly decreased in NLRP3-deficient mice as compared to wild-type controls. In all, NLRP3 plays a non-redundant role in vascular damage mediated neointima formation. Our data establish NLRP3 as a key player in the response to vascular damage, which could open new avenues to therapeutic intervention.

Critical role of nucleotide-binding oligomerization domain-like receptor 3 in vascular repair

Energy Technology Data Exchange (ETDEWEB)

Schlaweck, Sebastian; Zimmer, Sebastian; Struck, Rafael [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Bartok, Eva [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Werner, Nikos [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Bauernfeind, Franz [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Latz, Eicke [Institute of Innate Immunity, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Nickenig, Georg [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Hornung, Veit [Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany); Ghanem, Alexander, E-mail: ghanem@uni-bonn.de [Department of Medicine/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn (Germany)

2011-08-05

Highlights: {yields} NLRP3 is not required for systemic cardiovascular function in healthy mice. {yields} NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and that it does not alter peripheral differential blood counts. {yields} NLRP3 is critical in neointima formation following vascular injury. -- Abstract: Vascular remodeling characterized by hyperproliferative neointima formation is an unfavorable repair process that is triggered by vascular damage. This process is characterized by an increased local inflammatory and proliferative response that critically involves the pro-inflammatory cytokine interleukin-1{beta} (IL-1{beta}). IL-1{beta} is expressed and cytosolically retained as a procytokine that requires additional processing prior to exerting its pro-inflammatory function. Maturation and release of pro IL-1{beta} is governed by a cytosolic protein scaffold that is known as the inflammasome. Here we show that NLRP3 (NOD-like receptor family, pryin domain containing 3), an important activating component of the inflammasome, is involved in neointima formation after vascular injury. NLRP3 deficiency itself does not affect the functional cardiovascular phenotype and does not alter peripheral differential blood counts. However, neointima development following wire injury of the carotid artery was significantly decreased in NLRP3-deficient mice as compared to wild-type controls. In all, NLRP3 plays a non-redundant role in vascular damage mediated neointima formation. Our data establish NLRP3 as a key player in the response to vascular damage, which could open new avenues to therapeutic intervention.

Examining the role of dissolved organic nitrogen in stream ecosystems across biomes and Critical Zone gradients

Science.gov (United States)

Wymore, A.; Rodriguez-Cardona, B.; Coble, A. A.; Potter, J.; Lopez Lloreda, C.; Perez Rivera, K.; De Jesus Roman, A.; Bernal, S.; Martí Roca, E.; Kram, P.; Hruska, J.; Prokishkin, A. S.; McDowell, W. H.

2016-12-01

Watershed nitrogen exports are often dominated by dissolved organic nitrogen (DON); yet, little is known about the role ambient DON plays in ecosystems. As an organic nutrient, DON may serve as either an energy source or as a nutrient source. One hypothesized control on DON is nitrate (NO3-) availability. Here we examine the interaction of NO3- and DON in streams across temperate forests, tropical rainforests, and Mediterranean and taiga biomes. Experimental streams also drain contrasting Critical Zones which provide gradients of vegetation, soil type and lithology (e.g. volcaniclastic, granitic, ultramafic, Siberian Traps Flood Basalt) in which to explore how the architecture of the Critical Zone affects microbial biogeochemical reactions. Streams ranged in background dissolved organic carbon (DOC) concentration (1-50 mg C/L) and DOC: NO3- ratios (10-2000). We performed a series of ecosystem-scale NO3- additions in multiple streams within each environment and measured the change in DON concentration. Results demonstrate that there is considerable temporal and spatial variation across systems with DON both increasing and decreasing in response to NO3- addition. Ecologically this suggests that DON can serve as both a nutrient source and an energy source to aquatic microbial communities. In contrast, DOC concentrations rarely changed in response to NO3- additions suggesting that the N-rich fraction of the ambient dissolved organic matter pool is more bioreactive than the C-rich fraction. Contrasting responses of the DON and DOC pools indicate different mechanisms controlling their respective cycling. It is likely that DON plays a larger role in ecosystems than previously recognized.

Criticality safety and facility design considerations

International Nuclear Information System (INIS)

Waltz, W.R.

1991-06-01

Operations with fissile material introduce the risk of a criticality accident that may be lethal to nearby personnel. In addition, concerns over criticality safety can result in substantial delays and shutdown of facility operations. For these reasons, it is clear that the prevention of a nuclear criticality accident should play a major role in the design of a nuclear facility. The emphasis of this report will be placed on engineering design considerations in the prevention of criticality. The discussion will not include other important aspects, such as the physics of calculating limits nor criticality alarm systems

Critical behavior of collapsing surfaces

DEFF Research Database (Denmark)

Olsen, Kasper; Sourdis, C.

2009-01-01

We consider the mean curvature evolution of rotationally symmetric surfaces. Using numerical methods, we detect critical behavior at the threshold of singularity formation resembling that of gravitational collapse. In particular, the mean curvature simulation of a one-parameter family of initial...... data reveals the existence of a critical initial surface that develops a degenerate neckpinch. The limiting flow of the type II singularity is accurately modeled by the rotationally symmetric translating soliton....

A genomewide screen for suppressors of Alu-mediated rearrangements reveals a role for PIF1.

Directory of Open Access Journals (Sweden)

Karen M Chisholm

Full Text Available Alu-mediated rearrangement of tumor suppressor genes occurs frequently during carcinogenesis. In breast cancer, this mechanism contributes to loss of the wild-type BRCA1 allele in inherited disease and to loss of heterozygosity in sporadic cancer. To identify genes required for suppression of Alu-mediated recombination we performed a genomewide screen of a collection of 4672 yeast gene deletion mutants using a direct repeat recombination assay. The primary screen and subsequent analysis identified 12 candidate genes including TSA, ELG1, and RRM3, which are known to play a significant role in maintaining genomic stability. Genetic analysis of the corresponding human homologs was performed in sporadic breast tumors and in inherited BRCA1-associated carcinomas. Sequencing of these genes in high risk breast cancer families revealed a potential role for the helicase PIF1 in cancer predisposition. PIF1 variant L319P was identified in three breast cancer families; importantly, this variant, which is predicted to be functionally damaging, was not identified in a large series of controls nor has it been reported in either dbSNP or the 1000 Genomes Project. In Schizosaccharomyces pombe, Pfh1 is required to maintain both mitochondrial and nuclear genomic integrity. Functional studies in yeast of human PIF1 L319P revealed that this variant cannot complement the essential functions of Pfh1 in either the nucleus or mitochondria. Our results provide a global view of nonessential genes involved in suppressing Alu-mediated recombination and implicate variation in PIF1 in breast cancer predisposition.

Transcriptomic analysis of Portunus trituberculatus reveals a critical role for WNT4 and WNT signalling in limb regeneration.

Science.gov (United States)

Liu, Lei; Fu, Yuanyuan; Zhu, Fang; Mu, Changkao; Li, Ronghua; Song, Weiwei; Shi, Ce; Ye, Yangfang; Wang, Chunlin

2018-06-05

The swimming crab (Portunus trituberculatus) is among the most economically important seawater crustacean species in Asia. Despite its commercial importance and being well-studied status, genomic and transcriptomic data are scarce for this crab species. In the present study, limb bud tissue was collected at different developmental stages post amputation for transcriptomic analysis. Illumina RNA-sequencing was applied to characterise the limb regeneration transcriptome and identify the most characteristic genes. A total of 289,018 transcripts were obtained by clustering and assembly of clean reads, producing 150,869 unigenes with an average length of 956 bp. Subsequent analysis revealed WNT signalling as the key pathway involved in limb regeneration, with WNT4 a key mediator. Overall, limb regeneration appears to be regulated by multiple signalling pathways, with numerous cell differentiation, muscle growth, moult, metabolism, and immune-related genes upregulated, including WNT4, LAMA, FIP2, FSTL5, TNC, HUS1, SWI5, NCGL, SLC22, PLA2, Tdc2, SMOX, GDH, and SMPD4. This is the first experimental study done on regenerating claws of P. trituberculatus. These findings expand existing sequence resources for crab species, and will likely accelerate research into regeneration and development in crustaceans, particularly functional studies on genes involved in limb regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

Envisioning the Third Sector's Welfare Role: Critical Discourse Analysis of 'Post-Devolution' Public Policy in the UK 1998-2012.

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Chaney, Paul; Wincott, Daniel

2014-12-01

Welfare state theory has struggled to come to terms with the role of the third sector. It has often categorized welfare states in terms of the pattern of interplay between state social policies and the structure of the labour market. Moreover, it has frequently offered an exclusive focus on state policy - thereby failing to substantially recognize the role of the formally organized third sector. This study offers a corrective view. Against the backdrop of the international shift to multi-level governance, it analyses the policy discourse of third sector involvement in welfare governance following devolution in the UK. It reveals the changing and contrasting ways in which post-devolution territorial politics envisions the sector's role as a welfare provider. The mixed methods analysis compares policy framing and the structural narratives associated with the development of the third sector across the four constituent polities of the UK since 1998. The findings reveal how devolution has introduced a new spatial policy dynamic. Whilst there are elements of continuity between polities - such as the increasing salience of the third sector in welfare provision - policy narratives also provide evidence of the territorialization of third sector policy. From a methodological standpoint, this underlines the distinctive and complementary role discourse-based analysis can play in understanding contemporary patterns and processes shaping welfare governance.

Resilience? Insights into the role of Critical Infrastructures Disaster Mitigation Strategies

Directory of Open Access Journals (Sweden)

Sara Bouchon

2012-11-01

Full Text Available Critical infrastructures (CI systems provide essential services “for the maintenance of critical societal functions, including the supply chain, health, safety, security and economic or social well-being of the people” (European Commission, 2008. These systems are exposed to a great number of hazards and threats, which may result in severe consequences for the population, the socio-economic system, and the environment. The issue is particularly relevant at urban level, where the disruption of one CI system can propagate to the other systems and paralyze the entire area. It is therefore necessary, not only to protect CIs through Critical Infrastructure Protection (CIP strategies, but also to enhance the resilience of these areas. This article aims thus at providing some insights related to the evolution of the critical infrastructures disaster mitigation strategies from the sole protection towards resilience: what kind of strategies based on resilience can be developed to address CIs disruption at local or regional level? To what extent do these strategies contribute to increase the resilience level of the entire urban or metropolitan area? The first section focuses on the urban critical infrastructures systems as well as on the way their disruption can impact urban areas. The second section provides with some examples of key measures to operationalize resilience in the field of critical infrastructure disaster mitigation strategies. The last section highlights how the key measures developed to enhance the resilience against CI disruptions can benefit also to broader urban resilience. 

Hmong Parents’ Critical Reflections on Their Children’s Heritage Language Maintenance

Directory of Open Access Journals (Sweden)

Terry Yang

2008-01-01

Full Text Available This study utilizes a qualitative method to explore the critical reflections of Hmong parents helping their children maintain their native language. Specifically, it examines parents’ thoughts, feelings and experiences related to Hmong language maintenance. Findings reveal that Hmong parents worry about their children losing their ability to speak their native language. They believe that maintaining the Hmong language provides advantages in achieving academic success, attaining careers, and continuing to serve as role models in the community. Parents stressed the need to use Hmong at home in order to help their children develop and maintain the language. They reported some successes in doing so, while acknowledging several challenges.

Proteomic and physiological analyses reveal the role of exogenous spermidine on cucumber roots in response to Ca(NO3)2 stress.

Science.gov (United States)

Du, Jing; Guo, Shirong; Sun, Jin; Shu, Sheng

2018-05-01

The mechanism of exogenous Spd-induced Ca(NO 3 ) 2 stress tolerance in cucumber was studied by proteomics and physiological analyses. Protein-protein interaction network revealed 13 key proteins involved in Spd-induced Ca(NO 3 ) 2 stress resistance. Ca(NO 3 ) 2 stress is one of the major reasons for secondary salinization that limits cucumber plant development in greenhouse. The conferred protective role of exogenous Spd on cucumber in response to Ca(NO 3 ) 2 stress cues involves changes at the cellular and physiological levels. To investigate the molecular foundation of exogenous Spd in Ca(NO 3 ) 2 stress tolerance, a proteomic approach was performed in our work. After a 9 days period of Ca(NO 3 ) 2 stress and/or exogenous Spd, 71 differential protein spots were confidently identified. The resulting proteins were enriched in seven different categories of biological processes, including protein metabolism, carbohydrate and energy metabolism, ROS homeostasis and stress defense, cell wall related, transcription, others and unknown. Protein metabolism (31.2%), carbohydrate and energy metabolism (15.6%), ROS homeostasis and stress defense (32.5%) were the three largest functional categories in cucumber root and most of them were significantly increased by exogenous Spd. The Spd-responsive protein interaction network revealed 13 key proteins, whose accumulation changes could be critical for Spd-induced resistance; all 13 proteins were upregulated by Spd at transcriptional and protein levels in response to Ca(NO 3 ) 2 stress. Furthermore, accumulation of antioxidant enzymes, non-enzymatic antioxidant and polyamines, along with reduction of H 2 O 2 and MDA, were detected after exogenous Spd application during Ca(NO 3 ) 2 stress. The results of these proteomic and physiological analyses in cucumber root may facilitate a better understanding of the underlying mechanism of Ca(NO 3 ) 2 stress tolerance mediated by exogenous Spd.

Dictionary criticism and lexicographical function theory

DEFF Research Database (Denmark)

Tarp, Sven

2017-01-01

This contribution discusses dictionary criticism in the light of the function theory. It starts analyzing the objective of dictionary criticism and lists eight of the most important purposes with which criticism has been made by supporters of the function theory. It then discusses the two main...... types of dictionary criticism, namely criticism of other authors’ dictionaries and self-criticism of one’s own dictionaries. Based on this discussion, it proceeds to a definition of the concept of dictionary criticism which is above all considered a theory-based activity, the outcome of which may...... by the supporters of the function theory, and the way it could be presented in order to create debate. Finally, the contribution indicates the important role dictionary criticism has had in the development of the function theory and endorses an open and critical discussion culture within lexicography....

Determining the Role of Hydraulic Redistribution Regimes in the Critical Zone

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Lee, E.; Kumar, P.; Barron-Gafford, G.; Scott, R. L.; Hendryx, S.; Sanchez-Canete, E. P.

2015-12-01

A primary challenge in critical zone science is to understand and predict the interaction between aboveground and belowground ecohydrologic processes. We study the role of hydraulic redistribution (HR) by roots as a mechanism for facilitating aboveground-belowground interactions that drive water and carbon dynamics and the development of emergent spatial patterns of soil moisture and vegetation distribution. By linking field measurements of stem, taproot, and lateral root sap flux, with a shared resource model where the soil is a common reservoir, we examine competitive and facilitative dependencies between the co-occurring plant species. We used trenching as a means of severing any HR connectivity between overstory and understory plants in a subset of plots. We monitored leaf- level transpiration, photosynthesis, sub-canopy ET, NEE, soil evaporation, and soil respiration for trenched and un-trenched (control) trees in a dryland savanna that lacks access to stable soil moisture sources. HR in the trees at the site is detected, but the implications of HR on overstory-understory interactions and resulting spatial patterns and gradients remain untested. During an inter-storm period of the rainy season, we observed hydraulic lift, which may be increasing water availability to understory. Understory grasses may survive inter-storm dry periods by way of facilitative dependency on water resources supplied by overstory trees. On the other hand, immediately after storms we observe hydraulic descent that may be reducing water availability for the understory. Modeling is incorporated to capture the competitive and facilitative interaction between aboveground and belowground as detected in the field. This study provides deep insights for dryland regions, which enables broader generalizations regarding the interaction between groundwater, vegetation roots and aboveground assemblage and their role in whole-ecosystem performance.

Critical role of NADPH oxidase in neuronal oxidative damage and microglia activation following traumatic brain injury.

Directory of Open Access Journals (Sweden)

Quan-Guang Zhang

Full Text Available BACKGROUND: Oxidative stress is known to play an important role in the pathology of traumatic brain injury. Mitochondria are thought to be the major source of the damaging reactive oxygen species (ROS following TBI. However, recent work has revealed that the membrane, via the enzyme NADPH oxidase can also generate the superoxide radical (O(2(-, and thereby potentially contribute to the oxidative stress following TBI. The current study thus addressed the potential role of NADPH oxidase in TBI. METHODOLOGY/PRINCIPAL FINDINGS: The results revealed that NADPH oxidase activity in the cerebral cortex and hippocampal CA1 region increases rapidly following controlled cortical impact in male mice, with an early peak at 1 h, followed by a secondary peak from 24-96 h after TBI. In situ localization using oxidized hydroethidine and the neuronal marker, NeuN, revealed that the O(2(- induction occurred in neurons at 1 h after TBI. Pre- or post-treatment with the NADPH oxidase inhibitor, apocynin markedly inhibited microglial activation and oxidative stress damage. Apocynin also attenuated TBI-induction of the Alzheimer's disease proteins β-amyloid and amyloid precursor protein. Finally, both pre- and post-treatment of apocynin was also shown to induce significant neuroprotection against TBI. In addition, a NOX2-specific inhibitor, gp91ds-tat was also shown to exert neuroprotection against TBI. CONCLUSIONS/SIGNIFICANCE: As a whole, the study demonstrates that NADPH oxidase activity and superoxide production exhibit a biphasic elevation in the hippocampus and cortex following TBI, which contributes significantly to the pathology of TBI via mediation of oxidative stress damage, microglial activation, and AD protein induction in the brain following TBI.

Immunonutrition: the role of taurine.

LENUS (Irish Health Repository)

Redmond, H P

2012-02-03

Taurine is a sulfonated beta amino acid derived from methionine and cysteine metabolism. It is present in high concentrations in most tissues and in particular in proinflammatory cells such as polymorphonuclear phagocytes. Initial investigation into the multifaceted properties of this non-toxic physiologic amino acid revealed a link between retinal dysfunction and dietary deficiency. Since then a role for this amino acid has been found in membrane stabilization, bile salt formation, antioxidation, calcium homeostasis, growth modulation, and osmoregulation. Our own group has demonstrated a key role for taurine in modulation of apoptosis in a variety of cell types. This review summarizes our current knowledge of taurine in nutrition, host proinflammatory cell homeostasis, therapeutic applications, and its potential immunoregulatory properties. It is our belief that taurine, similar to arginine and glutamine, is now more than worthy of critical clinical analysis.

Matrix metalloproteinase-2 plays a critical role in overload induced skeletal muscle hypertrophy.

Science.gov (United States)

Zhang, Qia; Joshi, Sunil K; Lovett, David H; Zhang, Bryon; Bodine, Sue; Kim, Hubert T; Liu, Xuhui

2014-01-01

extracellular matrix (ECM) components are instrumental in maintaining homeostasis and muscle fiber functional integrity. Skeletal muscle hypertrophy is associated with ECM remodeling. Specifically, recent studies have reported the involvement of matrix metalloproteinases (MMPs) in muscle ECM remodeling. However, the functional role of MMPs in muscle hypertrophy remains largely unknown. in this study, we examined the role of MMP-2 in skeletal muscle hypertrophy using a previously validated method where the plantaris muscle of mice were subjected to mechanical overload due to the surgical removal of synergist muscles (gastrocnemius and soleus). following two weeks of overload, we observed a significant increase in MMP-2 activity and up-regulation of ECM components and remodeling enzymes in the plantaris muscles of wild-type mice. However, MMP-2 knockout mice developed significantly less hypertrophy and ECM remodeling in response to overload compared to their wild-type littermates. Investigation of protein synthesis rate and Akt/mTOR signaling revealed no difference between wild-type and MMP-2 knockout mice, suggesting that a difference in hypertrophy was independent of protein synthesis. taken together, our results suggest that MMP-2 is a key mediator of ECM remodeling in the setting of skeletal muscle hypertrophy.

Critical opalescence in baryonic QCD matter.

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Antoniou, N G; Diakonos, F K; Kapoyannis, A S; Kousouris, K S

2006-07-21

We show that critical opalescence, a clear signature of second-order phase transition in conventional matter, manifests itself as critical intermittency in QCD matter produced in experiments with nuclei. This behavior is revealed in transverse momentum spectra as a pattern of power laws in factorial moments, to all orders, associated with baryon production. This phenomenon together with a similar effect in the isoscalar sector of pions (sigma mode) provide us with a set of observables associated with the search for the QCD critical point in experiments with nuclei at high energies.

Critical Opalescence in Baryonic QCD Matter

Science.gov (United States)

Antoniou, N. G.; Diakonos, F. K.; Kapoyannis, A. S.; Kousouris, K. S.

2006-07-01

We show that critical opalescence, a clear signature of second-order phase transition in conventional matter, manifests itself as critical intermittency in QCD matter produced in experiments with nuclei. This behavior is revealed in transverse momentum spectra as a pattern of power laws in factorial moments, to all orders, associated with baryon production. This phenomenon together with a similar effect in the isoscalar sector of pions (sigma mode) provide us with a set of observables associated with the search for the QCD critical point in experiments with nuclei at high energies.

Critical Opalescence in Baryonic QCD Matter

International Nuclear Information System (INIS)

Antoniou, N. G.; Diakonos, F. K.; Kapoyannis, A. S.; Kousouris, K. S.

2006-01-01

We show that critical opalescence, a clear signature of second-order phase transition in conventional matter, manifests itself as critical intermittency in QCD matter produced in experiments with nuclei. This behavior is revealed in transverse momentum spectra as a pattern of power laws in factorial moments, to all orders, associated with baryon production. This phenomenon together with a similar effect in the isoscalar sector of pions (sigma mode) provide us with a set of observables associated with the search for the QCD critical point in experiments with nuclei at high energies

Chain networking revealed by molecular dynamics simulation

Science.gov (United States)

Zheng, Yexin; Tsige, Mesfin; Wang, Shi-Qing

Based on Kremer-Grest model for entangled polymer melts, we demonstrate how the response of a polymer glass depends critically on the chain length. After quenching two melts of very different chain lengths (350 beads per chain and 30 beads per chain) into deeply glassy states, we subject them to uniaxial extension. Our MD simulations show that the glass of long chains undergoes stable necking after yielding whereas the system of short chains is unable to neck and breaks up after strain localization. During ductile extension of the polymer glass made of long chain significant chain tension builds up in the load-bearing strands (LBSs). Further analysis is expected to reveal evidence of activation of the primary structure during post-yield extension. These results lend support to the recent molecular model 1 and are the simulations to demonstrate the role of chain networking. This work is supported, in part, by a NSF Grant (DMR-EAGER-1444859)

The views of key leaders in South Africa on implementation of family medicine: critical role in the district health system.

Science.gov (United States)

Moosa, Shabir; Mash, Bob; Derese, Anselme; Peersman, Wim

2014-06-25

Integrated team-based primary care is an international imperative. This is required more so in Africa, where fragmented verticalised care dominates. South Africa is trying to address this with health reforms, including Primary Health Care Re-engineering. Family physicians are already contributing to primary care despite family medicine being only fully registered as a full specialty in South Africa in 2008. However the views of leaders on family medicine and the role of family physicians is not clear, especially with recent health reforms. The aim of this study was to understand the views of key government and academic leaders in South Africa on family medicine, roles of family physicians and human resource issues. This was a qualitative study with academic and government leaders across South Africa. In-depth interviews were conducted with sixteen purposively selected leaders using an interview guide. Thematic content analysis was based on the framework method. Whilst family physicians were seen as critical to the district health system there was ambivalence on their leadership role and 'specialist' status. National health reforms were creating both threats and opportunities for family medicine. Three key roles for family physicians emerged: supporting referrals; clinical governance/quality improvement; and providing support to community-oriented care. Respondents' urged family physicians to consolidate the development and training of family physicians, and shape human resource policy to include family physicians. Family physicians were seen as critical to the district health system in South Africa despite difficulties around their precise role. Whilst their role was dominated by filling gaps at district hospitals to reduce referrals it extended to clinical governance and developing community-oriented primary care - a tall order, requiring strong teamwork. Innovative team-based service delivery is possible despite human resource challenges, but requires family

The critical role of NIR spectroscopy and statistical process control (SPC) strategy towards captopril tablets (25 mg) manufacturing process understanding: a case study.

Science.gov (United States)

Curtivo, Cátia Panizzon Dal; Funghi, Nathália Bitencourt; Tavares, Guilherme Diniz; Barbosa, Sávio Fujita; Löbenberg, Raimar; Bou-Chacra, Nádia Araci

2015-05-01

In this work, near-infrared spectroscopy (NIRS) method was used to evaluate the uniformity of dosage units of three captopril 25 mg tablets commercial batches. The performance of the calibration method was assessed by determination of Q value (0.9986), standard error of estimation (C-set SEE = 1.956), standard error of prediction (V-set SEP = 2.076) as well as the consistency (106.1%). These results indicated the adequacy of the selected model. The method validation revealed the agreement of the reference high pressure liquid chromatography (HPLC) and NIRS methods. The process evaluation using the NIRS method showed that the variability was due to common causes and delivered predictable results consistently. Cp and Cpk values were, respectively, 2.05 and 1.80. These results revealed a non-centered process in relation to the average target (100% w/w), in the specified range (85-115%). The probability of failure was 21:100 million tablets of captopril. The NIRS in combination with the method of multivariate calibration, partial least squares (PLS) regression, allowed the development of methodology for the uniformity of dosage units evaluation of captopril tablets 25 mg. The statistical process control strategy associated with NIRS method as PAT played a critical role in understanding of the sources and degree of variation and its impact on the process. This approach led towards a better process understanding and provided the sound scientific basis for its continuous improvement.

The evolution of an unsteady translating nonlinear rossby-wave critical layer

Science.gov (United States)

Haynes, Peter H.; Cowley, Stephen J.

When a monochromatic Rossby wave is forced on a flow which is slowly varying in time, the location of the critical line, where the phase speed of the wave is equal to that of the flow, also slowly changes. It is shown that this translation can play an important role in the vorticity balance near the critical line. The behavior of the translating critical layer is analyzed for various values of y, a parameter which measures the relative importance of nonlinear advection and translation. First, the vorticity equation in the critical layer is solved numerically in an important special case, where the velocity field in the critical layer is independent of the vorticity distribution and constant in time. The solutions reveal a number of new aspects of the behavior which are introduced by the translation, including the formation of a wake behind the critical layer, and the possibility of "trapping" of fluid particles in the critical layer if y exceeds a threshold value. Viewed in a frame of reference moving with the critical line the vorticity distribution may tend to a steady state, except in a "vorticity front" far downstream in the wake. If streamlines in the critical layer are open this steady state may be a predominantly inviscid one; if they are closed a steady state is possible only with non-zero dissipation. For both the unsteady and steady flows the translation allows the "logarithmic phase jump" across the critical layer, 4, to be non-zero and negative. Hence, even when the viscosity is vanishingly small, the critical layer can act as a strong "absorber" of Eliassen-Palm wave activity. Second, steady-state solutions are obtained numerically for a case when the velocity field in the critical layer is not independent of the vorticity distribution there. The interaction restricts the formation of closed streamlines, and an asymptotic open-streamline solution for large y can be found. The critical layer again acts an absorber of wave activity, but with decreasing e

Editorial Commentary: Hip Arthroscopy Plays a Role in Painful Hip Resurfacing Arthroplasty but a Prearthroscopy Diagnosis Is Critical to Outcome.

Science.gov (United States)

Rossi, Michael J

2016-03-01

Whereas hip arthroscopy plays a role in the investigation and treatment of the painful hip resurfacing arthroplasty, a diagnosis before arthroscopy is critical to improved outcome. The rate of conversion to total hip arthroplasty jumps from 7% to 37% when a pre-arthroscopy diagnosis is not known. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Automatic morphological subtyping reveals new roles of caspases in mitochondrial dynamics.

Directory of Open Access Journals (Sweden)

Jyh-Ying Peng

2011-10-01

Full Text Available Morphological dynamics of mitochondria is associated with key cellular processes related to aging and neuronal degenerative diseases, but the lack of standard quantification of mitochondrial morphology impedes systematic investigation. This paper presents an automated system for the quantification and classification of mitochondrial morphology. We discovered six morphological subtypes of mitochondria for objective quantification of mitochondrial morphology. These six subtypes are small globules, swollen globules, straight tubules, twisted tubules, branched tubules and loops. The subtyping was derived by applying consensus clustering to a huge collection of more than 200 thousand mitochondrial images extracted from 1422 micrographs of Chinese hamster ovary (CHO cells treated with different drugs, and was validated by evidence of functional similarity reported in the literature. Quantitative statistics of subtype compositions in cells is useful for correlating drug response and mitochondrial dynamics. Combining the quantitative results with our biochemical studies about the effects of squamocin on CHO cells reveals new roles of Caspases in the regulatory mechanisms of mitochondrial dynamics. This system is not only of value to the mitochondrial field, but also applicable to the investigation of other subcellular organelle morphology.

Who should be responsible for supporting individuals with mental health problems? A critical literature review.

Science.gov (United States)

Pope, Megan A; Malla, Ashok K; Iyer, Srividya N

2018-05-01

Individuals with mental health problems have many support needs that are often inadequately met; however, perceptions of who should be responsible for meeting these needs have been largely unexplored. Varying perceptions may influence whether, how, and to what extent relevant stakeholders support individuals with mental health problems. To critically evaluate the literature to determine who different stakeholders believe should be responsible for supporting individuals with mental health problems, what factors shape these perceptions, and how they relate to one another. A critical literature review was undertaken. Following an extensive literature search, the conceptual contributions of relevant works were critically evaluated. A concept map was created to build a conceptual framework of the topic. Views of individual versus societal responsibility for need provision and health; the morality of caring; and attributions of responsibility for mental illness offered valuable understandings of the review questions. Creating a concept map revealed that various interrelated factors may influence perceptions of responsibility. Varying perceptions of who should be responsible for supporting individuals with mental health problems may contribute to unmet support needs among this group. Our critical review helps build a much-needed conceptual framework of factors influencing perceptions of responsibility. Such a framework is essential as these views iteratively shape and reflect the complex divisions of mental healthcare roles and responsibilities. Understanding these perceptions can help define relevant stakeholders' roles more clearly, which can improve mental health services and strengthen stakeholder accountability.

The Future Role of GIS Education in Creating Critical Spatial Thinkers

Science.gov (United States)

Bearman, Nick; Jones, Nick; André, Isabel; Cachinho, Herculano Alberto; DeMers, Michael

2016-01-01

Teaching of critical spatial thinking in higher education empowers graduates to effectively engage with spatial data. Geographic information systems (GIS) and science are taught to undergraduates across many disciplines; we evaluate how this contributes to critical spatial thinking. The discipline of GIS covers the whole process of spatial…

THE ROLE OF THE SCHOOL CURRICULUM IN HUMAN DEVELOPMENT: CONTRIBUTIONS OF HISTORICAL AND CRITICAL PEDAGOGY AND PSYCHOLOGY OF HISTORICAL AND CULTURAL

Directory of Open Access Journals (Sweden)

Julia Malanchen

2013-12-01

Full Text Available This work points to the articulations between the fundamentals of cultural-historical psychology and the historical-critical pedagogy, in regard the issue of content that should compose the curriculum. The correct organization of the teaching process by the teacher, through scientific knowledge, as well as the appropriation of classic content, by students, promotes mental development to raise the development of higher psychological functions at their highest possibilities. Thus, we affirm the cultural-historical psychology and the historical-critical pedagogy align themselves both with regard to the Marxist perspective of socialist revolution, as in respect to concept of formation of individuality and the role of schooling in human emancipation.

Microsatellite variability reveals high genetic diversity and low genetic differentiation in a critical giant panda population

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Jiandong YANG, Zhihe ZHANG, Fujun SHEN, Xuyu YANG, Liang ZHANG, Limin CHEN, Wenping ZHANG, Qing ZHU, Rong HOU

2011-12-01

Full Text Available Understanding present patterns of genetic diversity is critical in order to design effective conservation and management strategies for endangered species. Tangjiahe Nature Reserve (NR is one of the most important national reserves for giant pandas Ailuropoda melanoleuca in China. Previous studies have shown that giant pandas in Tangjiahe NR may be threatened by population decline and fragmentation. Here we used 10 microsatellite DNA markers to assess the genetic variability in the Tangjiahe population. The results indicate a low level of genetic differentiation between the Hongshihe and Motianling subpopulations in the reserve. Assignment tests using the Bayesian clustering method in STRUCTURE identified one genetic cluster from 42 individuals of the two subpopulations. All individuals from the same subpopulation were assigned to one cluster. This indicates high gene flow between subpopulations. F statistic analyses revealed a low FIS-value of 0.024 in the total population and implies a randomly mating population in Tangjiahe NR. Additionally, our data show a high level of genetic diversity for the Tangjiahe population. Mean allele number (A, Allelic richness (AR and mean expected heterozygosity (HE for the Tangjiahe population was 5.9, 5.173 and 0.703, respectively. This wild giant panda population can be restored through concerted effort [Current Zoology 57 (6: 717–724, 2011].

Depletion of Plasmodium berghei plasmoredoxin reveals a non-essential role for life cycle progression of the malaria parasite.

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Buchholz, Kathrin; Rahlfs, Stefan; Schirmer, R Heiner; Becker, Katja; Matuschewski, Kai

2008-06-25

Proliferation of the pathogenic Plasmodium asexual blood stages in host erythrocytes requires an exquisite capacity to protect the malaria parasite against oxidative stress. This function is achieved by a complex antioxidant defence system composed of redox-active proteins and low MW antioxidants. Here, we disrupted the P. berghei plasmoredoxin gene that encodes a parasite-specific 22 kDa member of the thioredoxin superfamily. The successful generation of plasmoredoxin knockout mutants in the rodent model malaria parasite and phenotypic analysis during life cycle progression revealed a non-vital role in vivo. Our findings suggest that plasmoredoxin fulfils a specialized and dispensable role for Plasmodium and highlights the need for target validation to inform drug development strategies.

Simple analytical model reveals the functional role of embodied sensorimotor interaction in hexapod gaits

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Aoi, Shinya; Nachstedt, Timo; Manoonpong, Poramate; Wörgötter, Florentin; Matsuno, Fumitoshi

2018-01-01

Insects have various gaits with specific characteristics and can change their gaits smoothly in accordance with their speed. These gaits emerge from the embodied sensorimotor interactions that occur between the insect’s neural control and body dynamic systems through sensory feedback. Sensory feedback plays a critical role in coordinated movements such as locomotion, particularly in stick insects. While many previously developed insect models can generate different insect gaits, the functional role of embodied sensorimotor interactions in the interlimb coordination of insects remains unclear because of their complexity. In this study, we propose a simple physical model that is amenable to mathematical analysis to explain the functional role of these interactions clearly. We focus on a foot contact sensory feedback called phase resetting, which regulates leg retraction timing based on touchdown information. First, we used a hexapod robot to determine whether the distributed decoupled oscillators used for legs with the sensory feedback generate insect-like gaits through embodied sensorimotor interactions. The robot generated two different gaits and one had similar characteristics to insect gaits. Next, we proposed the simple model as a minimal model that allowed us to analyze and explain the gait mechanism through the embodied sensorimotor interactions. The simple model consists of a rigid body with massless springs acting as legs, where the legs are controlled using oscillator phases with phase resetting, and the governed equations are reduced such that they can be explained using only the oscillator phases with some approximations. This simplicity leads to analytical solutions for the hexapod gaits via perturbation analysis, despite the complexity of the embodied sensorimotor interactions. This is the first study to provide an analytical model for insect gaits under these interaction conditions. Our results clarified how this specific foot contact sensory

The role of CDX2 in intestinal homeostasis and inflammation

DEFF Research Database (Denmark)

Coskun, Mehmet; Troelsen, Jesper Thorvald; Nielsen, Ole Haagen

2011-01-01

a causal role in a large number of diseases and developmental disorders. Inflammatory bowel disease (IBD) is characterized by a chronically inflamed mucosa caused by dysregulation of the intestinal immune homeostasis. The aetiology of IBD is thought to be a combination of genetic and environmental factors......, including luminal bacteria. The Caudal-related homeobox transcription factor 2 (CDX2) is critical in early intestinal differentiation and has been implicated as a master regulator of the intestinal homeostasis and permeability in adults. When expressed, CDX2 modulates a diverse set of processes including...... of the intestinal homeostasis and further to reveal its potential role in inflammation....

Metabolomics analysis reveals the metabolic and functional roles of flavonoids in light-sensitive tea leaves.

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Zhang, Qunfeng; Liu, Meiya; Ruan, Jianyun

2017-03-20

As the predominant secondary metabolic pathway in tea plants, flavonoid biosynthesis increases with increasing temperature and illumination. However, the concentration of most flavonoids decreases greatly in light-sensitive tea leaves when they are exposed to light, which further improves tea quality. To reveal the metabolism and potential functions of flavonoids in tea leaves, a natural light-sensitive tea mutant (Huangjinya) cultivated under different light conditions was subjected to metabolomics analysis. The results showed that chlorotic tea leaves accumulated large amounts of flavonoids with ortho-dihydroxylated B-rings (e.g., catechin gallate, quercetin and its glycosides etc.), whereas total flavonoids (e.g., myricetrin glycoside, epigallocatechin gallate etc.) were considerably reduced, suggesting that the flavonoid components generated from different metabolic branches played different roles in tea leaves. Furthermore, the intracellular localization of flavonoids and the expression pattern of genes involved in secondary metabolic pathways indicate a potential photoprotective function of dihydroxylated flavonoids in light-sensitive tea leaves. Our results suggest that reactive oxygen species (ROS) scavenging and the antioxidation effects of flavonoids help chlorotic tea plants survive under high light stress, providing new evidence to clarify the functional roles of flavonoids, which accumulate to high levels in tea plants. Moreover, flavonoids with ortho-dihydroxylated B-rings played a greater role in photo-protection to improve the acclimatization of tea plants.

Suppressing Structural Colors of Photocatalytic Optical Coatings on Glass: The Critical Role of SiO2.

Science.gov (United States)

Li, Ronghua; Boudot, Mickael; Boissière, Cédric; Grosso, David; Faustini, Marco

2017-04-26

The appearance of structural colors on coated-glass is a critical esthetical drawback toward industrialization of photocatalytic coatings on windows for architecture or automobile. Herein we describe a rational approach to suppress the structural color of mesoporous TiO 2 -based coatings preserving photoactivity and mechanical stiffness. Addition of SiO 2 as third component is discussed. Ti x Si (1-x) O 2 mesoporous coatings were fabricated by one-step liquid deposition process through the evaporation induced self-assembling and characterized by GI-SAXS, GI-WAXS, electron microscopies, and in situ Environmental Ellipsometry Porosimetry. Guided by optical simulation, we investigated the critical role of SiO 2 on the optical responses of the films but also on the structural, mechanical, and photocatalytic properties, important requirements to go toward real applications. We demonstrate that adding SiO 2 to porous TiO 2 allows tuning and suppression of structural colors through refractive index matching and up to 160% increase in mechanical stiffening of the films. This study leads us to demonstrate an example of "invisible" coating, in which the light reflection is angle- and thickness-independent, and exhibiting high porosity, mechanical stiffness, and photoactivity.

Quantitative proteomic study of Aspergillus Fumigatus secretome revealed deamidation of secretory enzymes.

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Adav, Sunil S; Ravindran, Anita; Sze, Siu Kwan

2015-04-24

Aspergillus sp. plays an essential role in lignocellulosic biomass recycling and is also exploited as cell factories for the production of industrial enzymes. This study profiled the secretome of Aspergillus fumigatus when grown with cellulose, xylan and starch by high throughput quantitative proteomics using isobaric tags for relative and absolute quantification (iTRAQ). Post translational modifications (PTMs) of proteins play a critical role in protein functions. However, our understanding of the PTMs in secretory proteins is limited. Here, we present the identification of PTMs such as deamidation of secreted proteins of A. fumigatus. This study quantified diverse groups of extracellular secreted enzymes and their functional classification revealed cellulases and glycoside hydrolases (32.9%), amylases (0.9%), hemicellulases (16.2%), lignin degrading enzymes (8.1%), peptidases and proteases (11.7%), chitinases, lipases and phosphatases (7.6%), and proteins with unknown function (22.5%). The comparison of quantitative iTRAQ results revealed that cellulose and xylan stimulates expression of specific cellulases and hemicellulases, and their abundance level as a function of substrate. In-depth data analysis revealed deamidation as a major PTM of key cellulose hydrolyzing enzymes like endoglucanases, cellobiohydrolases and glucosidases. Hemicellulose degrading endo-1,4-beta-xylanase, monosidases, xylosidases, lignin degrading laccase, isoamyl alcohol oxidase and oxidoreductases were also found to be deamidated. The filamentous fungi play an essential role in lignocellulosic biomass recycling and fungal strains belonging to Aspergillus were also exploited as cell factories for the production of organic acids, pharmaceuticals, and industrially important enzymes. In this study, extracellular proteins secreted by thermophilic A. fumigatus when grown with cellulose, xylan and starch were profiled using isobaric tags for relative and absolute quantification (iTRAQ) by

Resveratrol and diabetes: A critical review of clinical studies.

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Öztürk, Ebru; Arslan, Ayşe Kübra Karaboğa; Yerer, Mükerrem Betül; Bishayee, Anupam

2017-11-01

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia. The disease results from the defects of insulin secretion and/or action. Resveratrol is a non-flavonoid polyphenol that naturally occurs as phytoalexin. The shell and stem of Vitis vinifera L. (Vitaceae) are the richest source of this compound. In addition to various in vitro and in vivo studies revealing the effectiveness of resveratrol in DM, there are many clinical trials indicating that resveratrol has the potential to benefit in DM patients. The therapeutic action of this compound in relation to diabetes is complex and involves in several beneficial roles. In view of this, clinical studies are necessary to elucidate these roles. In the near future, the use of resveratrol, alone or in combination with current anti-diabetic therapies, might be a conventional approach to effectively manage DM or its complications. This mini-review provides a critical overview of currently available clinical studies examining the effects of resveratrol in DM last decade. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Altering critical depinning current via domain wall pile-up in magnetic nanowires

International Nuclear Information System (INIS)

Geng, Liwei D.; Jin, Yongmei M.

2015-01-01

An important role of domain wall pile-up in current-driven domain wall depinning in magnetic nanowires is revealed using micromagnetic simulations. It is found that the critical current for domain wall depinning can be substantially reduced and conveniently tuned by controlling domain wall number in the pile-up at pinning site, in analogy to dislocation pile-up responsible for Hall–Petch effect in mechanical strength. Domain wall pinning and depinning at an s-shape bend is considered, and the effects of curvature and current crowding in magnetic circuit on domain wall behaviors are discussed. - Highlights: • Advance fundamental knowledge of current-driven domain wall phenomena. • Provide a novel approach to drastically reduce the critical depinning current. • Solve an outstanding problem of effective control of domain wall pinning/depinning. • Report appealing new findings of magnetic domain wall pile-up mechanism. • Overcome the limitations of materials properties for domain wall-based devices

The role of melatonin in anaesthesia and critical care

Directory of Open Access Journals (Sweden)

Madhuri S Kurdi

2013-01-01

Full Text Available Melatonin is a neurohormone secreted by the pineal gland. It is widely present in both plant and animal sources. In several countries, it is sold over the counter as tablets and as food supplement or additive. Currently, it is most often used to prevent jet lag and to induce sleep. It has been and is being used in several clinical trials with different therapeutic approaches. It has sedative, analgesic, anti-inflammatory, anti-oxidative and chronobiotic effects. In the present review, the potential therapeutic benefits of melatonin in anaesthesia and critical care are presented. This article aims to review the physiological properties of melatonin and how these could prove useful for several clinical applications in perioperative management, critical care and pain medicine. The topic was handsearched from textbooks and journals and electronically from PubMed, and Google scholar using text words.

The role of melatonin in anaesthesia and critical care.

Science.gov (United States)

Kurdi, Madhuri S; Patel, Tushar

2013-03-01

Melatonin is a neurohormone secreted by the pineal gland. It is widely present in both plant and animal sources. In several countries, it is sold over the counter as tablets and as food supplement or additive. Currently, it is most often used to prevent jet lag and to induce sleep. It has been and is being used in several clinical trials with different therapeutic approaches. It has sedative, analgesic, anti-inflammatory, anti-oxidative and chronobiotic effects. In the present review, the potential therapeutic benefits of melatonin in anaesthesia and critical care are presented. This article aims to review the physiological properties of melatonin and how these could prove useful for several clinical applications in perioperative management, critical care and pain medicine. The topic was handsearched from textbooks and journals and electronically from PubMed, and Google scholar using text words.

Critical behavior of electrical resistivity in amorphous Fe–Zr alloys

Indian Academy of Sciences (India)

Analysis of the resistivity data particularly in the critical region reveals that these systems have a much wider range of critical region compared to other crystalline ferromagnetic materials. The value of and specific heat critical exponent, has the same values as those determined from our earlier magnetic measurements ...

Critical Thinking as Integral to Social Work Practice

Science.gov (United States)

Gibbons, Jill; Gray, Mel

2004-01-01

The paper examines the role of critical thinking in an experience-based model of social work education. Within this model, the development of a critical approach to our own understanding of, as well as to existing knowledge about, the world is fundamental for students and educators alike. Critical thinking is defined as more than a rational,…

A survey on critical factors influencing agricultural insurance

Directory of Open Access Journals (Sweden)

Ali Valipour

2013-01-01

Full Text Available Agricultural business is a very high-risk job and an increase demand for agricultural products from one side and steady increase in production cost and weather changes, on the other side, have motivated many to use insurance for agricultural products. Insurance plays an important role in influencing crop production and insured satisfaction or farmers. The purpose of this research is to find critical components in agricultural insurance. Based on an exploration of the literature review and interviews, the proposed study of this paper extracts 24 variables and using factor analysis, we select the most important factors, which are grouped in seven categories. The implementation of our factor analysis has revealed uncertainty, moderator, market equilibrium, risky environment, empowering factor, education, training, structural hazards and natural ecosystems as the most important factors influencing agricultural industry.

The Role of Critical Pedagogy in the Globalization Era and the Aftermath of September 11, 2001. Interview with Peter McLaren

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Lucía Coral Aguirre Muñoz

2001-11-01

Full Text Available In the face of postmodern theories claiming the end of the working class, Peter McLaren discusses globalization as a form of imperialism; he does so from a critical perspective founded on the Marxist theory and on the concept of social class. Regarding the events of September 11, 2001, he describes U.S. foreign policy and its effects at the international level. He contrasts Bin Laden and Che Guevara, highlighting the differences between the two figures. The conclusion of his analysis defines the role of critical pedagogy in education, whose purpose is that of contributing to the creation of an egalitarian society based on the values of cooperation and solidarity.

Teaching materials: a critical position about the role they play in the language classroom

Directory of Open Access Journals (Sweden)

Araya Araya, Karla

2007-12-01

conceptual study about theoretical assumptions related to the importance and the role teaching materials have in the language teaching-learning process has been carried out. Also, there is a general analysis regarding the relationship among teaching materials, motivation and ideology. Finally, it can be concluded that materials are reproductions and constructors of certain discursive and ideological realities that usually favor the interests of the dominant classes. That is why a critical position about the role teaching materials have is necessary to prevent the reproduction of prejudices and common sense assumptions about language and society.

A ChIP-chip approach reveals a novel role for transcription factor IRF1 in the DNA damage response.

Science.gov (United States)

Frontini, Mattia; Vijayakumar, Meeraa; Garvin, Alexander; Clarke, Nicole

2009-03-01

IRF1 is a transcription factor that regulates key processes in the immune system and in tumour suppression. To gain further insight into IRF1's role in these processes, we searched for new target genes by performing chromatin immunoprecipitation coupled to a CpG island microarray (ChIP-chip). Using this approach we identified 202 new IRF1-binding sites with high confidence. Functional categorization of the target genes revealed a surprising cadre of new roles that can be linked to IRF1. One of the major functional categories was the DNA damage response pathway. In order to further validate our findings, we show that IRF1 can regulate the mRNA expression of a number of the DNA damage response genes in our list. In particular, we demonstrate that the mRNA and protein levels of the DNA repair protein BRIP1 [Fanconi anemia gene J (FANC J)] are upregulated after IRF1 over-expression. We also demonstrate that knockdown of IRF1 by siRNA results in loss of BRIP1 expression, abrogation of BRIP1 foci after DNA interstrand crosslink (ICL) damage and hypersensitivity to the DNA crosslinking agent, melphalan; a characteristic phenotype of FANC J cells. Taken together, our data provides a more complete understanding of the regulatory networks controlled by IRF1 and reveals a novel role for IRF1 in regulating the ICL DNA damage response.

A ChIP–chip approach reveals a novel role for transcription factor IRF1 in the DNA damage response

Science.gov (United States)

Frontini, Mattia; Vijayakumar, Meeraa; Garvin, Alexander; Clarke, Nicole

2009-01-01

IRF1 is a transcription factor that regulates key processes in the immune system and in tumour suppression. To gain further insight into IRF1's role in these processes, we searched for new target genes by performing chromatin immunoprecipitation coupled to a CpG island microarray (ChIP–chip). Using this approach we identified 202 new IRF1-binding sites with high confidence. Functional categorization of the target genes revealed a surprising cadre of new roles that can be linked to IRF1. One of the major functional categories was the DNA damage response pathway. In order to further validate our findings, we show that IRF1 can regulate the mRNA expression of a number of the DNA damage response genes in our list. In particular, we demonstrate that the mRNA and protein levels of the DNA repair protein BRIP1 [Fanconi anemia gene J (FANC J)] are upregulated after IRF1 over-expression. We also demonstrate that knockdown of IRF1 by siRNA results in loss of BRIP1 expression, abrogation of BRIP1 foci after DNA interstrand crosslink (ICL) damage and hypersensitivity to the DNA crosslinking agent, melphalan; a characteristic phenotype of FANC J cells. Taken together, our data provides a more complete understanding of the regulatory networks controlled by IRF1 and reveals a novel role for IRF1 in regulating the ICL DNA damage response. PMID:19129219

A critical role of the nuclear receptor HR3 in regulation of gonadotrophic cycles of the mosquito Aedes aegypti.

Directory of Open Access Journals (Sweden)

Daniel Mane-Padros

Full Text Available The orphan nuclear receptor HR3 is essential for developmental switches during insect development and metamorphosis regulated by 20-hydroxyecdysone (20E. Reproduction of female mosquitoes of the major vector of Dengue fever, Aedes aegypti, is cyclic because of its dependence on blood feeding. 20E is an important hormone regulating vitellogenic events in this mosquito; however, any role for HR3 in 20E-driven reproductive events has not been known. Using RNA interference (RNAi approach, we demonstrated that Aedes HR3 plays a critical role in a timely termination of expression of the vitellogenin (Vg gene encoding the major yolk protein precursor. It is also important for downregulation of the Target-of-Rapamycin pathway and activation of programmed autophagy in the Aedes fat body at the end of vitellogenesis. HR3 is critical in activating betaFTZ-F1, EcRB and USPA, the expressions of which are highly elevated at the end of vitellogenesis. RNAi depletion of HR3 (iHR3 prior to the first gonadotrophic cycle affects a normal progression of the second gonadotrophic cycle. Most of ovaries 24 h post second blood meal from iHR3 females in the second cycle were small with follicles that were only slightly different in length from of those of resting stage. In addition, these iHR3 females laid a significantly reduced number of eggs per mosquito as compared to those of iMal and the wild type. Our results indicate an important role of HR3 in regulation of 20E-regulated developmental switches during reproductive cycles of A. aegypti females.

Developing Critical Thinking through Student Consulting Projects

Science.gov (United States)

Canziani, Bonnie; Tullar, William L.

2017-01-01

The authors present survey results from faculty at 44 universities on the role of student consulting projects in developing business students' critical thinking. They conclude that students can improve critical thinking by engaging in guided primary and secondary research to inform their business assumptions that underpin business planning and…

The Development of Self-Criticism and Dependency in Early Adolescence and Their Role in the Development of Depressive and Anxiety Symptoms.

Science.gov (United States)

Kopala-Sibley, Daniel C; Zuroff, David C; Hankin, Benjamin L; Abela, John R Z

2015-08-01

According to Blatt and others (e.g., A. T. Beck), self-definition, or one's sense of self, and one's sense of relatedness to others represent core lifespan developmental tasks. This study examined the role of events pertaining to self-definition or relatedness in the development of personality traits from each domain (self-criticism and dependency), and their relationship to the development of depressive and anxiety symptoms. Two hundred seventy-six early adolescents completed a measure of self-criticism and dependency at baseline and again 24 months later, along with measures of depressive and anxiety symptoms. Every 3 months, participants completed a measure of life events, which were coded as self-definitional or relatedness oriented (80% rater agreement, kappa = .70). Structural equation models showed that self-definitional events predicted increases in self-criticism, which in turn predicted increases in depressive symptoms, whereas relatedness events predicted increases in dependency, although dependency was unrelated to change in symptoms. © 2015 by the Society for Personality and Social Psychology, Inc.

Adenosine A1 receptors (A1Rs) play a critical role in osteoclast formation and function

Science.gov (United States)

Kara, Firas M.; Chitu, Violeta; Sloane, Jennifer; Axelrod, Matthew; Fredholm, Bertil B.; Stanley, E. Richard; Cronstein, Bruce N.

2010-01-01

Adenosine regulates a wide variety of physiological processes via interaction with one or more G-protein-coupled receptors (A1R, A2AR, A2BR, and A3R). Because A1R occupancy promotes fusion of human monocytes to form giant cells in vitro, we determined whether A1R occupancy similarly promotes osteoclast function and formation. Bone marrow cells (BMCs) were harvested from C57Bl/6 female mice or A1R-knockout mice and their wild-type (WT) littermates and differentiated into osteoclasts in the presence of colony stimulating factor-1 and receptor activator of NF-κB ligand in the presence or absence of the A1R antagonist 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX). Osteoclast morphology was analyzed in tartrate-resistant acid phosphatase or F-actin-stained samples, and bone resorption was evaluated by toluidine blue staining of dentin. BMCs from A1R-knockout mice form fewer osteoclasts than BMCs from WT mice, and the A1R antagonist DPCPX inhibits osteoclast formation (IC50=1 nM), with altered morphology and reduced ability to resorb bone. A1R blockade increased ubiquitination and degradation of TRAF6 in RAW264.7 cells induced to differentiate into osteoclasts. These studies suggest a critical role for adenosine in bone homeostasis via interaction with adenosine A1R and further suggest that A1R may be a novel pharmacologic target to prevent the bone loss associated with inflammatory diseases and menopause.—Kara, F. M., Chitu, V., Sloane, J., Axelrod, M., Fredholm, B. B., Stanley, R., Cronstein, B. N. Adenosine A1 receptors (A1Rs) play a critical role in osteoclast formation and function. PMID:20181934

Nurses' role transition from the clinical ward environment to the critical care environment.

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Gohery, Patricia; Meaney, Teresa

2013-12-01

To explore the experiences of nurses moving from the ward environment to the critical care environment. Critical care areas are employing nurses with no critical care experience due to staff shortage. There is a paucity of literature focusing on the experiences of nurses moving from the ward environment to the critical care environment. A Heideggerian phenomenology research approach was used in this study. In-depth semi structured interviews, supported with an interview guide, were conducted with nine critical care nurses. Data analysis was guided by Van Manen (1990) approach to phenomenological analysis. Four main themes emerged: The highs and lows, you need support, theory-practice gap, struggling with fear. The participants felt ill prepared and inexperienced to work within the stressful and technical environment of critical care due to insufficient education and support. The study findings indicated that a variety of feelings and emotions are experienced by ward nurses who move into the stressful and technical environment of critical care due to insufficient skills and knowledge. More education and support is required to improve this transition process. Copyright © 2013 Elsevier Ltd. All rights reserved.

Microtubule-Mediated Inositol Lipid Signaling Plays Critical Roles in Regulation of Blebbing.

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Tatsuroh Sugiyama

Full Text Available Cells migrate by extending pseudopods such as lamellipodia and blebs. Although the signals leading to lamellipodia extension have been extensively investigated, those for bleb extension remain unclear. Here, we investigated signals for blebbing in Dictyostelium cells using a newly developed assay to induce blebbing. When cells were cut into two pieces with a microneedle, the anucleate fragments vigorously extended blebs. This assay enabled us to induce blebbing reproducibly, and analyses of knockout mutants and specific inhibitors identified candidate molecules that regulate blebbing. Blebs were also induced in anucleate fragments of leukocytes, indicating that this assay is generally applicable to animal cells. After cutting, microtubules in the anucleate fragments promptly depolymerized, followed by the extension of blebs. Furthermore, when intact cells were treated with a microtubule inhibitor, they frequently extended blebs. The depolymerization of microtubules induced the delocalization of inositol lipid phosphatidylinositol 3,4,5-trisphosphate from the cell membrane. PI3 kinase-null cells frequently extended blebs, whereas PTEN-null cells extended fewer blebs. From these observations, we propose a model in which microtubules play a critical role in bleb regulation via inositol lipid metabolism.

Role of Stat in Skin Carcinogenesis: Insights Gained from Relevant Mouse Models

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Macias, E.; Rao, D.; DiGiovanni, J.; DiGiovanni, J.; DiGiovanni, J.

2013-01-01

Signal transducer and activator of transcription 3 (Stat) is a cytoplasmic protein that is activated in response to cytokines and growth factors and acts as a transcription factor. Stat plays critical roles in various biological activities including cell proliferation, migration, and survival. Studies using keratinocyte-specific Stat-deficient mice have revealed that Stat plays an important role in skin homeostasis including keratinocyte migration, wound healing, and hair follicle growth. Use of both constitutive and inducible keratinocyte-specific Stat-deficient mouse models has demonstrated that Stat is required for both the initiation and promotion stages of multistage skin carcinogenesis. Further studies using a transgenic mouse model with a gain of function mutant of Stat (Stat3C) expressed in the basal layer of the epidermis revealed a novel role for Stat in skin tumor progression. Studies using similar Stat-deficient and gain-of-function mouse models have indicated its similar roles in ultraviolet B (UVB) radiation-mediated skin carcinogenesis. This paper summarizes the use of these various mouse models for studying the role and underlying mechanisms for the function of Stat in skin carcinogenesis. Given its significant role throughout the skin carcinogenesis process, Stat is an attractive target for skin cancer prevention and treatment.

Evolving towards a critical point: A possible electromagnetic way in which the critical regime is reached as the rupture approaches

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P. G. Kapiris

2003-01-01

Full Text Available In analogy to the study of critical phase transitions in statistical physics, it has been argued recently that the fracture of heterogeneous materials could be viewed as a critical phenomenon, either at laboratory or at geophysical scales. If the picture of the development of the fracture is correct one may guess that the precursors may reveal the critical approach of the main-shock. When a heterogeneous material is stretched, its evolution towards breaking is characterized by the appearance of microcracks before the final  break-up. Microcracks produce both acoustic and electromagnetic(EM emission in the frequency range from VLF to VHF. The microcracks and the associated acoustic and EM activities constitute the so-called precursors of general fracture. These precursors are detectable not only at laboratory but also at geophysical scales. VLF and VHF acoustic and EM emissions have been reported resulting from volcanic and seismic activities in various geologically distinct regions of the world. In the present work we attempt to establish the hypothesis that the evolution of the Earth's crust towards the critical point takes place not only in a mechanical but also in an electromagnetic sense. In other words, we focus on the possible electromagnetic criticality, which is reached while the catastrophic rupture in the Earth's crust approaches. Our main tool is the monitoring of micro-fractures that occur before the final breakup, by recording their radio-electromagnetic emissions. We show that the spectral power law analysis of the electromagnetic precursors reveals distinguishing signatures of underlying critical dynamics, such as: (i the emergence of memory effects; (ii the decrease with time of the anti-persistence behaviour; (iii the presence of persistence properties in the tail of the sequence of the precursors; and (iv the acceleration of the precursory electro-magnetic energy release. Moreover, the statistical analysis of the amplitudes of

The Role of Critical Pedagogy in the Globalization Era and the Aftermath of September 11, 2001. Interview with Peter McLaren (Updated Version

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Lucía Coral Aguirre Muñoz

2003-05-01

Full Text Available In the face of postmodern theories claiming the end of the working class, Peter McLaren discusses the globalization of capitalism as a form of imperialism; he does so from a critical perspective founded on Marxist theory and on the concepts of social class and class struggle. Regarding the events of September 11, 2001, he describes U.S. foreign policy and its effects at the international level. He also defends the heroic figure of Che Guevara against accusations by some US critics that Che should be compared to Bin Laden. The conclusion of this analysis defines the role of critical pedagogy in education, whose purpose is that of contributing to the creation of an egalitarian society based on the socialist values of cooperation and solidarity.

Field transcriptome revealed critical developmental and physiological transitions involved in the expression of growth potential in japonica rice

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Kamatsuki Kaori

2011-01-01

Full Text Available Abstract Background Plant growth depends on synergistic interactions between internal and external signals, and yield potential of crops is a manifestation of how these complex factors interact, particularly at critical stages of development. As an initial step towards developing a systems-level understanding of the biological processes underlying the expression of overall agronomic potential in cereal crops, a high-resolution transcriptome analysis of rice was conducted throughout life cycle of rice grown under natural field conditions. Results A wide range of gene expression profiles based on 48 organs and tissues at various developmental stages identified 731 organ/tissue specific genes as well as 215 growth stage-specific expressed genes universally in leaf blade, leaf sheath, and root. Continuous transcriptome profiling of leaf from transplanting until harvesting further elucidated the growth-stage specificity of gene expression and uncovered two major drastic changes in the leaf transcriptional program. The first major change occurred before the panicle differentiation, accompanied by the expression of RFT1, a putative florigen gene in long day conditions, and the downregulation of the precursors of two microRNAs. This transcriptome change was also associated with physiological alterations including phosphate-homeostasis state as evident from the behavior of several key regulators such as miR399. The second major transcriptome change occurred just after flowering, and based on analysis of sterile mutant lines, we further revealed that the formation of strong sink, i.e., a developing grain, is not the major cause but is rather a promoter of this change. Conclusions Our study provides not only the genetic basis for functional genomics in rice but also new insight into understanding the critical physiological processes involved in flowering and seed development, that could lead to novel strategies for optimizing crop productivity.

Does gender influence outcomes in critically ill patients?

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Angele, Martin K; Pratschke, Sebastian; Chaudry, Irshad H

2012-01-01

Investigators continue to debate whether gender plays any role in patient outcome following injury/critical illness. We submit that age and hormonal milieu at the time of injury, rather than gender, are the critical factors influencing patient outcome under those conditions.

Critical Pedagogy, Internationalisation, and a Third Space: Cultural Tensions Revealed in Students' Discourse

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Pitts, Margaret Jane; Brooks, Catherine F.

2017-01-01

Set within the context of a global pursuit towards the internationalisation of higher education, this paper critically examines student discourse in a globally connected classroom between learners in the USA and Singapore. It makes salient some of the cultural assumptions and tensions that undergird students' discourse in collaborative…

Critical Opalescence in Baryonic QCD Matter

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Antoniou, N. G.; Diakonos, F. K.; Kapoyannis, A. S.; Kousouris, K. S.

2006-01-01

We show that critical opalescence, a clear signature of second-order phase transition in conventional matter, manifests itself as critical intermittency in QCD matter produced in experiments with nuclei. This behaviour is revealed in transverse momentum spectra as a pattern of power laws in factorial moments, to all orders, associated with baryon production. This phenomenon together with a similar effect in the isoscalar sector of pions (sigma mode) provide us with a set of observables associ...

Critical role of constitutive type I interferon response in bronchial epithelial cell to influenza infection.

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Alan C-Y Hsu

Full Text Available Innate antiviral responses in bronchial epithelial cells (BECs provide the first line of defense against respiratory viral infection and the effectiveness of this response is critically dependent on the type I interferons (IFNs. However the importance of the antiviral responses in BECs during influenza infection is not well understood. We profiled the innate immune response to infection with H3N2 and H5N1 virus using Calu-3 cells and primary BECs to model proximal airway cells. The susceptibility of BECs to influenza infection was not solely dependent on the sialic acid-bearing glycoprotein, and antiviral responses that occurred after viral endocytosis was more important in limiting viral replication. The early antiviral response and apoptosis correlated with the ability to limit viral replication. Both viruses reduced RIG-I associated antiviral responses and subsequent induction of IFN-β. However it was found that there was constitutive release of IFN-β by BECs and this was critical in inducing late antiviral signaling via type I IFN receptors, and was crucial in limiting viral infection. This study characterizes anti-influenza virus responses in airway epithelial cells and shows that constitutive IFN-β release plays a more important role in initiating protective late IFN-stimulated responses during human influenza infection in bronchial epithelial cells.

Nurse's perceptions of physiotherapists in critical care team: Report of a qualitative study.

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Gupte, Pranati; Swaminathan, Narasimman

2016-03-01

Interprofessional relationship plays a major role in effective patient care. Specialized units such as critical care require multidisciplinary care where perception about every members role may affect the delivery of patient care. The objective of this study was to find out nurses' perceptions of the role of physiotherapists in the critical care team. Qualitative study by using semi-structured interview was conducted among the qualified nurses working in the Intensive Care Unit of a tertiary care hospital. The interview consisted of 19 questions divided into 3 sections. Interviews were audio recorded and transcribed. In-depth content analysis was carried out to identify major themes in relation to the research question. Analysis identified five major issues which included role and image of a physiotherapist, effectiveness of treatment, communications, teamwork, and interprofessional relations. Physiotherapists were perceived to be an important member of the critical team with the role of mobilizing the patients. The respondents admitted that there existed limitations in interprofessional relationship. Nurses perceived the role of physiotherapist in the critical care unit as an integral part and agreed on the need for inclusion of therapist multidisciplinary critical care team.

A critical role for the chimpanzee model in the study of hepatitis C.

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Bukh, Jens

2004-06-01

Chimpanzees remain the only recognized animal model for the study of hepatitis C virus (HCV). Studies performed in chimpanzees played a critical role in the discovery of HCV and are continuing to play an essential role in defining the natural history of this important human pathogen. In the absence of a reproducible cell culture system, the infectivity titer of HCV challenge pools can be determined only in chimpanzees. Recent studies in chimpanzees have provided new insight into the nature of host immune responses-particularly the intrahepatic responses-following primary and secondary experimental HCV infections. The immunogenicity and efficacy of vaccine candidates against HCV can be tested only in chimpanzees. Finally, it would not have been possible to demonstrate the infectivity of infectious clones of HCV without chimpanzees. Chimpanzees became infected when RNA transcripts from molecular clones were inoculated directly into the liver. The infection generated by such transfection did not differ significantly from that observed in animals infected intravenously with wild-type HCV. The RNA inoculated into chimpanzees originated from a single sequence, and the animals therefore had a monoclonal HCV infection. Monoclonal infection simplifies studies of HCV, because virus interaction with the host is not confounded by the quasispecies invariably present in a natural infection. It furthermore permits true homologous challenge in studies of protective immunity and in testing the efficacy of vaccine candidates. Finally, this in vivo transfection system has made it possible to test for the first time the importance of genetic elements for HCV infectivity.

Present knowledge and perspectives on the role of copper in brake materials and related environmental issues: A critical assessment.

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Straffelini, Giovanni; Ciudin, Rodica; Ciotti, Alessandro; Gialanella, Stefano

2015-12-01

This critical review presents several aspects related to the use of copper as a main component in brake pads in road vehicles. The compositions of these materials are attracting increasing interest and concern due to the relative contribution of wear products to particulate matter emissions in the environment as a result of braking action even though there has been a reduction in exhaust products from internal combustion engines. We review the data on the main wear mechanisms in brake systems and highlight the positive role of copper. However, similar to other heavy metal emissions, even the release of copper into the atmosphere may have important environmental and health effects. Thus, several replacement strategies are being pursued, and the positive and negative features will be critically reviewed. Additionally, the future perspectives in materials development will be discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exploration of critical thinking in dental hygiene education.

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Beistle, Kimberly S; Palmer, Louann Bierlein

2014-12-01

This qualitative study explores the perceptions of dental hygiene faculty regarding issues surrounding critical thinking skills integration within their associate degree dental hygiene programs. Twenty faculty participated in the study, as drawn from 11 accredited associate degree dental hygiene programs in one Midwest state. Multiple sources of data were collected, including email questionnaires, individual follow-up phone interviews and artifacts. Interpretive analysis was conducted. Data analysis revealed that faculty generally understood critical thinking, but interpretations varied. Most do not use varied teaching strategies to promote critical thinking skills, and focus on one particular strategy--that of case studies. The participants identified the need for allied health-focused faculty development opportunities, and noted that calibration of instruction was needed. Despite challenges, faculty felt responsible for teaching critical thinking skills, and identified the need for time to build critical thinking skills into the curriculum. This study was conducted in response to the American Dental Education Association Commission on Change and Innovation's challenge for dental hygiene educators to comprehend their own knowledge on the concept of critical thinking related to research-based pedagogical approaches to teaching and learning. Findings revealed a strong desire among the dental hygiene faculty in this study to incorporate critical thinking into their work. They want to do what they believe is the right thing, but their actual knowledge of the definitional and application theories about critical thinking is still in the early stages of development. Regular and targeted faculty development opportunities are needed. Copyright © 2014 The American Dental Hygienists’ Association.

An emerging role of pectic rhamnogalacturonanII for cell wall integrity

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Reboul, Rebecca; Tenhaken, Raimund

2012-01-01

The plant cell wall is a complex network of different polysaccharides and glycoproteins, showing high diversity in nature. The essential components, tethering cell wall are under debate, as novel mutants challenge established models. The mutant ugd2,3 with a reduced supply of the important wall precursor UDP-glucuronic acid reveals the critical role of the pectic compound rhamnogalacturonanII for cell wall stability. This polymer seems to be more important for cell wall integrity than the pre...

Critical Thinking in Social Work Education: A Research Synthesis

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Samson, Patricia L.

2016-01-01

In a meta-analytic review of critical thinking in social work education, findings revealed variability in research designs, methods, and subsequent findings. The 10 studies reviewed assessed different components of critical thinking and highlighted different potential moderator variables. Although there are significant limitations to all the…

The Impeding Role of Self-Critical Perfectionism on Therapeutic Alliance During Treatment and Eating Disorder Symptoms at Follow-up in Patients with an Eating Disorder

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Jolene van der Kaap-Deeder

2016-04-01

Full Text Available This study examines the impeding role of self-critical perfectionism at onset of treatment on therapeutic alliance during treatment and eating disorder symptoms at follow-up in patients with an eating disorder. Participants were 53 female patients with a mean age of 21.1 years treated for an eating disorder in a specialized inpatient treatment unit. Self-critical perfectionism was assessed at admission, therapeutic alliance was assessed during treatment (after three months of treatment, and eating disorder symptoms were assessed at admission, after three months and one year later. Self-critical perfectionism negatively related to treatment alliance with the therapist. Although self-critical perfectionism was not directly predictive of subsequent changes in eating disorder symptoms, it was indirectly related to less reduction in body dissatisfaction through the therapeutic alliance. These results point to the importance of self-critical perfectionism in the therapeutic alliance and in changes in body image problems. Treatment implications are discussed.

Mechanism of SOS PR-domain autoinhibition revealed by single-molecule assays on native protein from lysate.

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Lee, Young Kwang; Low-Nam, Shalini T; Chung, Jean K; Hansen, Scott D; Lam, Hiu Yue Monatrice; Alvarez, Steven; Groves, Jay T

2017-04-28

The guanine nucleotide exchange factor (GEF) Son of Sevenless (SOS) plays a critical role in signal transduction by activating Ras. Here we introduce a single-molecule assay in which individual SOS molecules are captured from raw cell lysate using Ras-functionalized supported membrane microarrays. This enables characterization of the full-length SOS protein, which has not previously been studied in reconstitution due to difficulties in purification. Our measurements on the full-length protein reveal a distinct role of the C-terminal proline-rich (PR) domain to obstruct the engagement of allosteric Ras independently of the well-known N-terminal domain autoinhibition. This inhibitory role of the PR domain limits Grb2-independent recruitment of SOS to the membrane through binding of Ras·GTP in the SOS allosteric binding site. More generally, this assay strategy enables characterization of the functional behaviour of GEFs with single-molecule precision but without the need for purification.

Analysis of Critical Parts and Materials

Science.gov (United States)

1980-12-01

1 1 1% 1% 1% 1% Large Orders Manual Ordering of Some Critical Parts Order Spares with Original Order Incentives Belter Capital Investment...demand 23 Large orders 24 Long lead procurement funding (including raw materials, facility funding) 25 Manpower analysis and training 26 Manual ... ordering of some critical parts 27 More active role in schedule negotiation 28 Multiple source procurements 29 Multi-year program funding 30 Order

Critical role of gap junction communication, calcium and nitric oxide signaling in bystander responses to focal photodynamic injury.

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Calì, Bianca; Ceolin, Stefano; Ceriani, Federico; Bortolozzi, Mario; Agnellini, Andrielly H R; Zorzi, Veronica; Predonzani, Andrea; Bronte, Vincenzo; Molon, Barbara; Mammano, Fabio

2015-04-30

Ionizing and nonionizing radiation affect not only directly targeted cells but also surrounding "bystander" cells. The underlying mechanisms and therapeutic role of bystander responses remain incompletely defined. Here we show that photosentizer activation in a single cell triggers apoptosis in bystander cancer cells, which are electrically coupled by gap junction channels and support the propagation of a Ca2+ wave initiated in the irradiated cell. The latter also acts as source of nitric oxide (NO) that diffuses to bystander cells, in which NO levels are further increased by a mechanism compatible with Ca(2+)-dependent enzymatic production. We detected similar signals in tumors grown in dorsal skinfold chambers applied to live mice. Pharmacological blockade of connexin channels significantly reduced the extent of apoptosis in bystander cells, consistent with a critical role played by intercellular communication, Ca2+ and NO in the bystander effects triggered by photodynamic therapy.

Value congruence and depressive symptoms among critical care clinicians: The mediating role of moral distress.

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Lamiani, Giulia; Dordoni, Paola; Argentero, Piergiorgio

2018-02-01

Clinicians working in intensive care units are often exposed to several job stressors that can negatively affect their mental health. Literature has acknowledged the role of value congruence and job control in determining clinicians' psychological well-being and depressive symptoms. However, potential mediators of this association have been scarcely examined. This study aimed to test the mediating role of moral distress in the relationship between value congruence and job control, on the one hand, and depression, on the other hand. A cross-sectional study involving physicians, nurses, and residents working in 7 intensive care units in the north of Italy was conducted. Clinicians were administered in the Italian Moral Distress Scale-Revised, the value and control subscales of the Areas of Worklife Scale, and the Beck Depression Inventory II. Structural equation modeling was used to test the mediation model. Analysis on 170 questionnaires (response rate 72%) found no relations between job control and moral distress. A total indirect effect of value congruence on depression through moral distress (β = -.12; p = .02) was found. Moral distress contributes to the development of depressive symptoms among critical care clinicians who perceive a value incongruence with their organization and therefore should be addressed. Copyright © 2017 John Wiley & Sons, Ltd.

Role of brain-derived neurotrophic factor in the excitatory-inhibitory imbalance during the critical period of postnatal respiratory development in the rat.

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Gao, Xiu-Ping; Zhang, Hanmeng; Wong-Riley, Margaret

2015-11-01

The critical period of respiratory development in rats is a narrow window toward the end of the second postnatal week (P12-13), when abrupt neurochemical, electrophysiological, and ventilatory changes occur, when inhibition dominates over excitation, and when the animals' response to hypoxia is the weakest. The goal of this study was to further test our hypothesis that a major mechanism underlying the synaptic imbalance during the critical period is a reduced expression of brain-derived neurotrophic factor (BDNF) and its TrkB receptors. Our aims were to determine (1) that the inhibitory dominance observed in hypoglossal motoneurons during the critical period was also demonstrable in a key respiratory chemosensor, NTSVL; (2) if in vivo application of a TrkB agonist, 7,8-DHF, would prevent, but a TrkB antagonist, ANA-12, would accentuate the synaptic imbalance; and (3) if hypoxia would also heighten the imbalance. Our results indicate that (1) the synaptic imbalance was evident in the NTSVL during the critical period; (2) intraperitoneal injections of 7,8-DHF prevented the synaptic imbalance during the critical period, whereas ANA-12 in vivo accentuated such an imbalance; and (3) acute hypoxia induced the weakest response in both the amplitude and frequency of sEPSCs during the critical period, but it increased the frequency of sIPSCs during the critical period. Thus, our findings are consistent with and strengthen our hypothesis that BDNF and TrkB play a significant role in inducing a synaptic imbalance during the critical period of respiratory development in the rat. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Critical Media and Communication Studies Today. A Conversation

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Christian Fuchs

2011-06-01

Full Text Available This article documents a conversation between us that was first published in parallel on our two blogs http://dwmw.wordpress.com and http://fuchs.uti.at/blog. The conversation deals with our assessments of the status of Critical Media and Communication Studies today. We discuss the work of Dallas Smythe, how to study and assess Google, research dimensions of Critical Political Economy of the Media, how important each of these dimensions should be, the role of ideology critique for Critical Political Economy of the Media, the commonalities and differences between Political Economies of the Media and Critical Political Economy of the Media/Critique of the Political Economy of the Media, the role of Karl Marx for Political Economies of the Media, Nicholas Garnham's recent comments on the field of Critical Political Economy of the Media, neoliberalism and capitalist crisis as contexts for Political Economies of the Media. Comments are very welcome on our blogs, URLs to the specific blog postings can be found in the article sections.

Envisioning the Third Sector's Welfare Role: Critical Discourse Analysis of ‘Post-Devolution’ Public Policy in the UK 1998–2012

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Chaney, Paul; Wincott, Daniel

2014-01-01

Welfare state theory has struggled to come to terms with the role of the third sector. It has often categorized welfare states in terms of the pattern of interplay between state social policies and the structure of the labour market. Moreover, it has frequently offered an exclusive focus on state policy – thereby failing to substantially recognize the role of the formally organized third sector. This study offers a corrective view. Against the backdrop of the international shift to multi-level governance, it analyses the policy discourse of third sector involvement in welfare governance following devolution in the UK. It reveals the changing and contrasting ways in which post-devolution territorial politics envisions the sector's role as a welfare provider. The mixed methods analysis compares policy framing and the structural narratives associated with the development of the third sector across the four constituent polities of the UK since 1998. The findings reveal how devolution has introduced a new spatial policy dynamic. Whilst there are elements of continuity between polities – such as the increasing salience of the third sector in welfare provision – policy narratives also provide evidence of the territorialization of third sector policy. From a methodological standpoint, this underlines the distinctive and complementary role discourse-based analysis can play in understanding contemporary patterns and processes shaping welfare governance. PMID:25574063

A Critical Role for the Nucleus Reuniens in Long-Term, But Not Short-Term Associative Recognition Memory Formation.

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Barker, Gareth R I; Warburton, Elizabeth Clea

2018-03-28

Recognition memory for single items requires the perirhinal cortex (PRH), whereas recognition of an item and its associated location requires a functional interaction among the PRH, hippocampus (HPC), and medial prefrontal cortex (mPFC). Although the precise mechanisms through which these interactions are effected are unknown, the nucleus reuniens (NRe) has bidirectional connections with each regions and thus may play a role in recognition memory. Here we investigated, in male rats, whether specific manipulations of NRe function affected performance of recognition memory for single items, object location, or object-in-place associations. Permanent lesions in the NRe significantly impaired long-term, but not short-term, object-in-place associative recognition memory, whereas single item recognition memory and object location memory were unaffected. Temporary inactivation of the NRe during distinct phases of the object-in-place task revealed its importance in both the encoding and retrieval stages of long-term associative recognition memory. Infusions of specific receptor antagonists showed that encoding was dependent on muscarinic and nicotinic cholinergic neurotransmission, whereas NMDA receptor neurotransmission was not required. Finally, we found that long-term object-in-place memory required protein synthesis within the NRe. These data reveal a specific role for the NRe in long-term associative recognition memory through its interactions with the HPC and mPFC, but not the PRH. The delay-dependent involvement of the NRe suggests that it is not a simple relay station between brain regions, but, rather, during high mnemonic demand, facilitates interactions between the mPFC and HPC, a process that requires both cholinergic neurotransmission and protein synthesis. SIGNIFICANCE STATEMENT Recognizing an object and its associated location, which is fundamental to our everyday memory, requires specific hippocampal-cortical interactions, potentially facilitated by the

Roles of TRPM8 Ion Channels in Cancer: Proliferation, Survival, and Invasion

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Nelson S. Yee

2015-10-01

Full Text Available The goal of this article is to provide a critical review of the transient receptor potential melastatin-subfamily member 8 (TRPM8 in cancers, with an emphasis on its roles in cellular proliferation, survival, and invasion. The TRPM8 ion channels regulate Ca²⁺ homeostasis and function as a cellular sensor and transducer of cold temperature. Accumulating evidence has demonstrated that TRPM8 is aberrantly expressed in a variety of malignant solid tumors. Clinicopathological analysis has shown that over-expression of TRPM8 correlates with tumor progression. Experimental data have revealed important roles of TRPM8 channels in cancer cells proliferation, survival, and invasion, which appear to be dependent on the cancer type. Recent reports have begun to reveal the signaling mechanisms that mediate the biological roles of TRPM8 in tumor growth and metastasis. Determining the mechanistic roles of TRPM8 in cancer is expected to elucidate the impact of thermal and chemical stimuli on the formation and progression of neoplasms. Translational research and clinical investigation of TRPM8 in malignant diseases will help exploit these ion channels as molecular biomarkers and therapeutic targets for developing precision cancer medicine.

The Role of Higher Harmonics In Musical Interval Perception

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Krantz, Richard; Douthett, Jack

2011-10-01

Using an alternative parameterization of the roughness curve we make direct use of critical band results to investigate the role of higher harmonics on the perception of tonal consonance. We scale the spectral amplitudes in the complex home tone and complex interval tone to simulate acoustic signals of constant energy. Our analysis reveals that even with a relatively small addition of higher harmonics the perfect fifth emerges as a consonant interval with more, musically important, just intervals emerging as consonant as more and more energy is shifted into higher frequencies.

The critical role of Golgi cells in regulating spatio-temporal integration and plasticity at the cerebellum input stage

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2008-07-01

Full Text Available After the discovery at the end of the 19th century (Golgi, 1883, the Golgi cell was precisely described by S.R. y Cajal (see Cajal, 1987, 1995 and functionally identified as an inhibitory interneuron 50 years later by J.C. Eccles and colleagues (Eccles e al., 1967. Then, its role has been casted by Marr (1969 within the Motor Learning Theory as a codon size regulator of granule cell activity. It was immediately clear that Golgi cells had to play a critical role, since they are the main inhibitory interneuron of the granular layer and control activity of as many as 100 millions granule cells. In vitro, Golgi cells show pacemaking, resonance, phase-reset and rebound-excitation in the theta-frequency band. These properties are likely to impact on their activity in vivo, which shows irregular spontaneous beating modulated by sensory inputs and burst responses to punctuate stimulation followed by a silent pause. Moreover, investigations have given insight into Golgi cells connectivity within the cerebellar network and on their impact on the spatio-temporal organization of activity. It turns out that Golgi cells can control both the temporal dynamics and the spatial distribution of information transmitted through the cerebellar network. Moreover, Golgi cells regulate the induction of long-term synaptic plasticity at the mossy fiber - granule cell synapse. Thus, the concept is emerging that Golgi cells are of critical importance for regulating granular layer network activity bearing important consequences for cerebellar computation as a whole.

Genesis of the "Critical-Acceleration of MOND" and Its Role in "Formation of Structures"

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Tank H. K.

2012-10-01

Full Text Available As an attempt to explain the “flattening of galaxies rotation-curves”, Milgrom proposed a Modification of Newtonian Dynamics MOND, in which he needed a new constant of nature a 0 , termed as “critical-acceleration-of MOND”, in his best-fit empirical formula. But so far it has been an ad-hoc introduction of a new constant. Whereas this article pro- poses: (i a genesis of this constant; (ii explains its recurrences in various physical sit- uations; and (iii its role in determining the size and radii of various structures, like: the electron, the proton, the nucleus-of-atom, the globular-clusters, the spiral-galaxies, the galactic-clusters and the whole universe. In this process we get a new interpretation of “the cosmological-red-shift”, that the linear part of the cosmological-red-shift may not be due to “metric-expansion-of-space”; and even the currently-believed “accelerated- expansion” may be slowing down with time.

Mechanistic studies of anticancer aptamer AS1411 reveal a novel role for nucleolin in regulating Rac1 activation.

Science.gov (United States)

Reyes-Reyes, E Merit; Šalipur, Francesca R; Shams, Mitra; Forsthoefel, Matthew K; Bates, Paula J

2015-08-01

AS1411 is a G-rich quadruplex-forming oligodeoxynucleotide that binds specifically to nucleolin, a protein found on the surface and in the cytoplasm of most malignant cells but absent from the surface/cytoplasm of most normal cells. AS1411 has shown promising clinical activity and is being widely used as a tumor-targeting agent, but its mechanism of action is not fully understood. Previously, we showed that AS1411 is taken up in cancer cells by macropinocytosis (fluid phase endocytosis) and subsequently stimulates further macropinocytosis by a nucleolin-dependent mechanism. In the current study, we have investigated the significance and molecular mechanisms of AS1411-induced macropinocytosis. Our results indicate that the antiproliferative activity of AS1411 in various cell lines correlated with its capacity to stimulate macropinocytosis. In DU145 prostate cancer cells, AS1411 induced activation of EGFR, Akt, p38, and Rac1. Activation of Akt and p38 were not critical for AS1411 activity because Akt activation was not observed in all AS1411-responsive cell lines and knockdown of p38 had no effect on AS1411's ability to inhibit proliferation. On the other hand, activation of EGFR and Rac1 appeared to play a role in AS1411 activity in all cancer cell lines examined (DU145, MDA-MB-468, A549, LNCaP) and their inhibition significantly reduced AS1411-mediated macropinocytosis and AS1411 antiproliferative activity. Interestingly, downregulation of nucleolin expression by siRNA also produced a substantial increase in activated Rac1, revealing a previously unknown role for nucleolin as a negative regulator of Rac1 activation. Our results are consistent with a model whereby AS1411 binding to nucleolin leads to sustained activation of Rac1 and causes methuosis, a novel type of nonapoptotic cell death characterized by hyperstimulation of macropinocytosis. We speculate that methuosis is a tumor/metastasis suppressor mechanism that opposes the malignant functions of Rac1 and that

Genome-Wide Identification and Expression Profiling of Cytokinin Oxidase/Dehydrogenase (CKX) Genes Reveal Likely Roles in Pod Development and Stress Responses in Oilseed Rape (Brassica napus L.).

Science.gov (United States)

Liu, Pu; Zhang, Chao; Ma, Jin-Qi; Zhang, Li-Yuan; Yang, Bo; Tang, Xin-Yu; Huang, Ling; Zhou, Xin-Tong; Lu, Kun; Li, Jia-Na

2018-03-16

Cytokinin oxidase/dehydrogenases (CKXs) play a critical role in the irreversible degradation of cytokinins, thereby regulating plant growth and development. Brassica napus is one of the most widely cultivated oilseed crops worldwide. With the completion of whole-genome sequencing of B. napus , genome-wide identification and expression analysis of the BnCKX gene family has become technically feasible. In this study, we identified 23 BnCKX genes and analyzed their phylogenetic relationships, gene structures, conserved motifs, protein subcellular localizations, and other properties. We also analyzed the expression of the 23 BnCKX genes in the B. napus cultivar Zhong Shuang 11 ('ZS11') by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), revealing their diverse expression patterns. We selected four BnCKX genes based on the results of RNA-sequencing and qRT-PCR and compared their expression in cultivated varieties with extremely long versus short siliques. The expression levels of BnCKX5-1 , 5-2 , 6-1 , and 7-1 significantly differed between the two lines and changed during pod development, suggesting they might play roles in determining silique length and in pod development. Finally, we investigated the effects of treatment with the synthetic cytokinin 6-benzylaminopurine (6-BA) and the auxin indole-3-acetic acid (IAA) on the expression of the four selected BnCKX genes. Our results suggest that regulating BnCKX expression is a promising way to enhance the harvest index and stress resistance in plants.

Investigating Predictive Role of Critical Thinking on Metacognition with Structural Equation Modeling

Science.gov (United States)

Arslan, Serhat

2015-01-01

The purpose of this study is to examine the relationships between critical thinking and metacognition. The sample of study consists of 390 university students who were enrolled in different programs at Sakarya University, in Turkey. In this study, the Critical Thinking Disposition Scale and Metacognitive Thinking Scale were used. The relationships…

On the role of cavitation in particle collection in flotation - A critical review. II

Energy Technology Data Exchange (ETDEWEB)

Zhou, Z.A.; Xu, Z.H.; Finch, J.A.; Masliyah, J.H.; Chow, R.S. [Alberta Research Council, Edmonton, AB (Canada)

2009-04-15

Research in applying hydrodynamic cavitation to recovery of natural resources during the last decade is reviewed. The existence and formation of tiny bubbles or gas nuclei (diameter from microns down to nano sizes) in natural water were verified from both direct and in-direct measurements, providing a foundation for applying hydrodynamic cavitation to flotation systems. The interactions between tiny bubbles and fine particles in aqueous slurry were analysed. Tiny bubbles generated by hydrodynamic cavitation increased contact angle of solids and hence attachment force, bridge fine particles to form aggregates, minimize slime coating, remove oxidation layers on particle surfaces, and in hence reduce reagents consumption. Experiments revealed that the energy dissipation levels for cavity formation in a flowing liquid could be much lower than predicted, depending on the content of dissolved gases, presence of free gas nuclei and design of cavitation tubes. Application of hydrodynamic cavitation to fine and coarse particle flotation, high intensity conditioning, oil agglomeration of fine coal, and oil sands processing has confirmed the role of tiny bubbles formed by cavitation in improving recovery efficiency. Increased flotation kinetics by hydrodynamic cavitation could be attributed to a dual role: some collapsing cavity bubbles serving to break interfacial layers on particle surfaces while other cavity bubbles attaching to those freshly exposed mineral surfaces. The role of water vapor and other gases within cavity bubbles in particle-bubble attachment remains to be explored. Incorporating hydrodynamic cavitation into flotation systems to take advantage of its unique features is expected to develop the next generation of flotation machines.

A critical systems perspective on the design of organizational space

NARCIS (Netherlands)

Mobach, Mark P.

2007-01-01

This paper is the first to introduce critical systems thinking into a new emerging research strand: the design of organizational space. The study revealed two things. First, critical systems thinking provides a thorough framework to understand the possibilities to connect organization and building;

Rapid centriole assembly in Naegleria reveals conserved roles for both de novo and mentored assembly.

Science.gov (United States)

Fritz-Laylin, Lillian K; Levy, Yaron Y; Levitan, Edward; Chen, Sean; Cande, W Zacheus; Lai, Elaine Y; Fulton, Chandler

2016-03-01

Centrioles are eukaryotic organelles whose number and position are critical for cilia formation and mitosis. Many cell types assemble new centrioles next to existing ones ("templated" or mentored assembly). Under certain conditions, centrioles also form without pre-existing centrioles (de novo). The synchronous differentiation of Naegleria amoebae to flagellates represents a unique opportunity to study centriole assembly, as nearly 100% of the population transitions from having no centrioles to having two within minutes. Here, we find that Naegleria forms its first centriole de novo, immediately followed by mentored assembly of the second. We also find both de novo and mentored assembly distributed among all major eukaryote lineages. We therefore propose that both modes are ancestral and have been conserved because they serve complementary roles, with de novo assembly as the default when no pre-existing centriole is available, and mentored assembly allowing precise regulation of number, timing, and location of centriole assembly. © 2016 Wiley Periodicals, Inc.

Gastric residual volume in critically ill patients: a dead marker or still alive?

Science.gov (United States)

Elke, Gunnar; Felbinger, Thomas W; Heyland, Daren K

2015-02-01

Early enteral nutrition (EN) is consistently recommended as first-line nutrition therapy in critically ill patients since it favorably alters outcome, providing both nutrition and nonnutrition benefits. However, critically ill patients receiving mechanical ventilation are at risk for regurgitation, pulmonary aspiration, and eventually ventilator-associated pneumonia (VAP). EN may increase these risks when gastrointestinal (GI) dysfunction is present. Gastric residual volume (GRV) is considered a surrogate parameter of GI dysfunction during the progression of enteral feeding in the early phase of critical illness and beyond. By monitoring GRV, clinicians may detect patients with delayed gastric emptying earlier and intervene with strategies that minimize or prevent VAP as one of the major risks of EN. The value of periodic GRV measurements with regard to risk reduction of VAP incidence has frequently been questioned in the past years. Increasing the GRV threshold before interrupting gastric feeding results in marginal increases in EN delivery. More recently, a large randomized clinical trial revealed that abandoning GRV monitoring did not negatively affect clinical outcomes (including VAP) in mechanically ventilated patients. The results have revived the discussion on the role of GRV monitoring in critically ill, mechanically ventilated patients receiving early EN. This review summarizes the most recent clinical evidence on the use of GRV monitoring in critically ill patients. Based on the clinical evidence, it discusses the pros and cons and further addresses whether GRV is a dead marker or still alive for the nutrition management of critically ill patients. © 2014 American Society for Parenteral and Enteral Nutrition.

A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control

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Gang Xin

2015-11-01

Full Text Available Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue “unhelped” CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells “help” the CD8 response during chronic infection via IL-21-induced BATF expression.

Politics of Ebola and the critical role of global health diplomacy for the CARICOM

Directory of Open Access Journals (Sweden)

Vijay Kumar Chattu

2017-01-01

Full Text Available The 2014 Ebola epidemic was the largest in history, affecting Guinea, Liberia, Sierra Leone, Nigeria, and Mali in West Africa. The International Health Regulations are legally binding in 194 countries including all the member states of WHO “to prevent, protect against, control, and provide a public health response to the international spread of disease.” Since the Caribbean Community region heavily depends on tourism, a single case of the disease anywhere in the region could have serious negative consequences for the rest of the region's tourism industry. Global health diplomacy brings together the disciplines of public health, international affairs, management, law, and economics and focuses on negotiations that shape and manage the global policy environment for health. The regional institutes such as Caribbean Public Health Agency should play a more proactive and pivotal role in the creation of regional response teams in all the island nations collaborating with the departments of public health and epidemiology at the regional campuses of The University of the West Indies. The role of global health diplomacy and its practice should be encouraged to reach a consensus among the stakeholders considering the threat to the health security in the region. There is a need for the cadre of global health diplomats who has a critical understanding of health and also the practice of diplomacy since such serious health issues have implications at the global level in this globalized world.

Implementation and evaluation of critical thinking strategies to enhance critical thinking skills in Middle Eastern nurses.

Science.gov (United States)

Simpson, Elaine; Courtney, Mary

2008-12-01

The purpose of this study was to develop, implement and evaluate critical thinking strategies to enhance critical thinking skills in Middle Eastern nurses. Critical thinking strategies such as questioning, debate, role play and small group activity were developed and used in a professional development programme, which was trialled on a sample of Middle Eastern nurses (n = 20), to promote critical thinking skills, encourage problem solving, development of clinical judgment making and care prioritization in order to improve patient care and outcomes. Classroom learning was transformed from memorization to interaction and active participation. The intervention programme was successful in developing critical thinking skills in both the nurse educators and student nurses in this programme. This programme successfully integrated critical thinking strategies into a Middle Eastern nursing curriculum. Recommendations are as follows: (1) utilize evidence-based practice and stem questions to encourage the formulation of critical thinking questions; (2) support the needs of nurse educators for them to effectively implement teaching strategies to foster critical thinking skills; and (3) adopt creative approaches to (i) transform students into interactive participants and (ii) open students' minds and stimulate higher-level thinking and problem-solving abilities.

CCR4-Not Complex Subunit Not2 Plays Critical Roles in Vegetative Growth, Conidiation and Virulence in Watermelon Fusarium Wilt Pathogen Fusarium oxysporum f. sp. niveum

Science.gov (United States)

Dai, Yi; Cao, Zhongye; Huang, Lihong; Liu, Shixia; Shen, Zhihui; Wang, Yuyan; Wang, Hui; Zhang, Huijuan; Li, Dayong; Song, Fengming

2016-01-01

CCR4-Not complex is a multifunctional regulator that plays important roles in multiple cellular processes in eukaryotes. In the present study, the biological function of FonNot2, a core subunit of the CCR4-Not complex, was explored in Fusarium oxysporum f. sp. niveum (Fon), the causal agent of watermelon wilt disease. FonNot2 was expressed at higher levels in conidia and germinating conidia and during infection in Fon-inoculated watermelon roots than in mycelia. Targeted disruption of FonNot2 resulted in retarded vegetative growth, reduced conidia production, abnormal conidial morphology, and reduced virulence on watermelon. Scanning electron microscopy observation of infection behaviors and qRT-PCR analysis of in planta fungal growth revealed that the ΔFonNot2 mutant was defective in the ability to penetrate watermelon roots and showed reduced fungal biomass in root and stem of the inoculated plants. Phenotypic and biochemical analyses indicated that the ΔFonNot2 mutant displayed hypersensitivity to cell wall perturbing agents (e.g., Congo Red and Calcofluor White) and oxidative stress (e.g., H2O2 and paraquat), decreased fusaric acid content, and reduced reactive oxygen species (ROS) production during spore germination. Our data demonstrate that FonNot2 plays critical roles in regulating vegetable growth, conidiogenesis and conidia morphology, and virulence on watermelon via modulating cell wall integrity, oxidative stress response, ROS production and FA biosynthesis through the regulation of transcription of genes involved in multiple pathways. PMID:27695445

Critical Fluctuations in Spatial Complex Networks

Science.gov (United States)

Bradde, Serena; Caccioli, Fabio; Dall'Asta, Luca; Bianconi, Ginestra

2010-05-01

An anomalous mean-field solution is known to capture the nontrivial phase diagram of the Ising model in annealed complex networks. Nevertheless, the critical fluctuations in random complex networks remain mean field. Here we show that a breakdown of this scenario can be obtained when complex networks are embedded in geometrical spaces. Through the analysis of the Ising model on annealed spatial networks, we reveal, in particular, the spectral properties of networks responsible for critical fluctuations and we generalize the Ginsburg criterion to complex topologies.

The Critical Role of Substrate in Stabilizing Phosphorene Nanoflake: A Theoretical Exploration.

Science.gov (United States)

Gao, Junfeng; Zhang, Gang; Zhang, Yong-Wei

2016-04-13

Phosphorene, a new two-dimensional (2D) semiconductor, has received much interest due to its robust direct band gap and high charge mobility. Currently, however, phosphorene can only be produced by mechanical or liquid exfoliation, and it is still a significant challenge to directly epitaxially grow phosphorene, which greatly hinders its mass production and, thus, applications. In epitaxial growth, the stability of nanoscale cluster or flake on a substrate is crucial. Here, we perform ab initio energy optimizations and molecular dynamics simulations to explore the critical role of substrate on the stability of a representative phosphorene flake. Our calculations show that the stability of the phosphorene nanoflake is strongly dependent on the interaction strength between the nanoflake and substrate. Specifically, the strong interaction (0.75 eV/P atom) with Cu(111) substrate breaks up the phosphorene nanoflake, while the weak interaction (0.063 eV/P atom) with h-BN substrate fails to stabilize its 2D structure. Remarkably, we find that a substrate with a moderate interaction (about 0.35 eV/P atom) is able to stabilize the 2D characteristics of the nanoflake on a realistic time scale. Our findings here provide useful guidelines for searching suitable substrates for the directly epitaxial growth of phosphorene.

The lipopolysaccharide core oligosaccharide of Burkholderia plays a critical role in maintaining a proper gut symbiosis with the bean bug Riptortus pedestris.

Science.gov (United States)

Kim, Jiyeun Kate; Jang, Ho Am; Kim, Min Seon; Cho, Jae Hyun; Lee, Junbeom; Di Lorenzo, Flaviana; Sturiale, Luisa; Silipo, Alba; Molinaro, Antonio; Lee, Bok Luel

2017-11-24

Lipopolysaccharide, the outer cell-wall component of Gram-negative bacteria, has been shown to be important for symbiotic associations. We recently reported that the lipopolysaccharide O-antigen of Burkholderia enhances the initial colonization of the midgut of the bean bug, Riptortus pedestris However, the midgut-colonizing Burkholderia symbionts lack the O-antigen but display the core oligosaccharide on the cell surface. In this study, we investigated the role of the core oligosaccharide, which directly interacts with the host midgut, in the Riptortus-Burkholderia symbiosis. To this end, we generated the core oligosaccharide mutant strains, Δ wabS , Δ wabO , Δ waaF, and Δ waaC, and determined the chemical structures of their oligosaccharides, which exhibited different compositions. The symbiotic properties of these mutant strains were compared with those of the wild-type and O-antigen-deficient Δ wbiG strains. Upon introduction into Riptortus via the oral route, the core oligosaccharide mutant strains exhibited different rates of colonization of the insect midgut. The symbiont titers in fifth-instar insects revealed significantly reduced population sizes of the inner core oligosaccharide mutant strains Δ waaF and Δ waaC These two strains also negatively affected host growth rate and fitness. Furthermore, R. pedestris individuals colonized with the Δ waaF and Δ waaC strains were vulnerable to septic bacterial challenge, similar to insects without a Burkholderia symbiont. Taken together, these results suggest that the core oligosaccharide from Burkholderia symbionts plays a critical role in maintaining a proper symbiont population and in supporting the beneficial effects of the symbiont on its host in the Riptortus-Burkholderia symbiosis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Critical behavior of ferromagnetic Ising thin films

International Nuclear Information System (INIS)

Cossio, P.; Mazo-Zuluaga, J.; Restrepo, J.

2006-01-01

In the present work, we study the magnetic properties and critical behavior of simple cubic ferromagnetic thin films. We simulate LxLxd films with semifree boundary conditions on the basis of the Monte Carlo method and the Ising model with nearest neighbor interactions. A Metropolis dynamics was implemented to carry out the energy minimization process. For different film thickness, in the nanometer range, we compute the temperature dependence of the magnetization, the magnetic susceptibility and the fourth order Binder's cumulant. Bulk and surface contributions of these quantities are computed in a differentiated fashion. Additionally, according to finite size scaling theory, we estimate the critical exponents for the correlation length, magnetic susceptibility, and magnetization. Results reveal a strong dependence of critical temperature and critical exponents on the film thickness. The obtained critical exponents are finally compared to those reported in literature for thin films

Teaching Critical Thinking in a Library Credit Course.

Science.gov (United States)

Poirier, Gayle; Hocker, Susan

1993-01-01

Discussion of critical thinking skills focuses on the academic library's role in teaching critical thinking skills based on experiences with a library resources course at Louisiana State University. Teaching techniques are discussed, sample lessons are described, and evaluation of students' research papers and student retention of skills are…

msiDBN: A Method of Identifying Critical Proteins in Dynamic PPI Networks

Directory of Open Access Journals (Sweden)

Yuan Zhang

2014-01-01

Full Text Available Dynamics of protein-protein interactions (PPIs reveals the recondite principles of biological processes inside a cell. Shown in a wealth of study, just a small group of proteins, rather than the majority, play more essential roles at crucial points of biological processes. This present work focuses on identifying these critical proteins exhibiting dramatic structural changes in dynamic PPI networks. First, a comprehensive way of modeling the dynamic PPIs is presented which simultaneously analyzes the activity of proteins and assembles the dynamic coregulation correlation between proteins at each time point. Second, a novel method is proposed, named msiDBN, which models a common representation of multiple PPI networks using a deep belief network framework and analyzes the reconstruction errors and the variabilities across the time courses in the biological process. Experiments were implemented on data of yeast cell cycles. We evaluated our network construction method by comparing the functional representations of the derived networks with two other traditional construction methods. The ranking results of critical proteins in msiDBN were compared with the results from the baseline methods. The results of comparison showed that msiDBN had better reconstruction rate and identified more proteins of critical value to yeast cell cycle process.

Nuclear criticality safety department training implementation

International Nuclear Information System (INIS)

Carroll, K.J.; Taylor, R.G.; Worley, C.A.

1996-01-01

The Nuclear Criticality Safety Department (NCSD) is committed to developing and maintaining a staff of qualified personnel to meet the current and anticipated needs in Nuclear Criticality Safety (NCS) at the Oak Ridge Y-12 Plant. The NCSD Qualification Program is described in Y/DD-694, Qualification Program, Nuclear Criticality Safety Department This document provides a listing of the roles and responsibilities of NCSD personnel with respect to training and details of the Training Management System (TMS) programs, Mentoring Checklists and Checksheets, as well as other documentation utilized to implement the program. This document supersedes Y/DD-696, Revision 2, dated 3/27/96, Training Implementation, Nuclear Criticality Safety Department. There are no backfit requirements associated with revisions to this document

Critical Pedagogy Principles in Teaching EFL Reading

Directory of Open Access Journals (Sweden)

Slamet Wahyudi Yulianto

2015-12-01

Full Text Available This study attempts to reveal how the use of critical pedagogy principles in teaching English as a Foreign Language (EFL reading facilitates students to think critically. Additionally, it investigates and elaborates the benefits and challenges of using critical pedagogy principles in teaching EFL reading. The three critical pedagogy principles used in this study were dialogic education, democratic classroom, and reading the world and the word. Critical thinking skills and dispositions expected to be performed by the participants were analysis and evaluation skills, open-mindedness, and making reasoned decision. This is a case study design which was conducted in the form of teaching program. The teaching program which consisted of eight meetings was given to 59 EFL sophomores in the Reading in Professional Context class at a private teacher education in Bandung. Data in the form of classroom talks and activities and students‟ responses as well as their critical thinking skills self-assessment were collected by using video recordings, observation notes, interview guideline, students‟ learning journals, and questionnaires. It is revealed that the teaching program has facilitated students to think critically by providing four categories of activity. They are (1 offering problematic topics and reading materials that are linked to the students‟ lives, (2 encouraging students to read between the lines, (3 distributing classroom power, and (4 creating space for students‟ voices to be heard. Meanwhile, there are two benefits of the teaching program, namely (1 language development and (2 new knowledge as well as experience acquisition. However, there are three major challenges in conducting the teaching program that are (1 the lack of classroom-friendly authentic controversial reading materials, (2 the passive culture, and (3 the unpredictable classroom.

Cyber Security Insider Threats :: Government’s Role in Protecting India’s Critical Infrastructure Sectors

OpenAIRE

Vohra, Pulkit

2014-01-01

This research identifies the problem of insider threats in the critical infrastructure sectors of India. It is structured to answer the research question: "Why insider threats should be the primary concern for Indian government to protect its critical infrastructure sectors.” It defines the critical infrastructure sectors and portrays the cyber security scenario of India. Also, through the research study, it identifies the lack of awareness and non-seriousness of employees in the critical sec...

Critical role for BIM in T cell receptor restimulation-induced death

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Fleisher Thomas A

2008-08-01

Full Text Available Abstract Background Upon repeated or chronic antigen stimulation, activated T cells undergo a T cell receptor (TCR-triggered propriocidal cell death important for governing the intensity of immune responses. This is thought to be chiefly mediated by an extrinsic signal through the Fas-FasL pathway. However, we observed that TCR restimulation still potently induced apoptosis when this interaction was blocked, or genetically impaired in T cells derived from autoimmune lymphoproliferative syndrome (ALPS patients, prompting us to examine Fas-independent, intrinsic signals. Results Upon TCR restimulation, we specifically noted a marked increase in the expression of BIM, a pro-apoptotic Bcl-2 family protein known to mediate lymphocyte apoptosis induced by cytokine withdrawal. In fact, T cells from an ALPS type IV patient in which BIM expression is suppressed were more resistant to restimulation-induced death. Strikingly, knockdown of BIM expression rescued normal T cells from TCR-induced death to as great an extent as Fas disruption. Conclusion Our data implicates BIM as a critical mediator of apoptosis induced by restimulation as well as growth cytokine withdrawal. These findings suggest an important role for BIM in eliminating activated T cells even when IL-2 is abundant, working in conjunction with Fas to eliminate chronically stimulated T cells and maintain immune homeostasis. Reviewers This article was reviewed by Dr. Wendy Davidson (nominated by Dr. David Scott, Dr. Mark Williams (nominated by Dr. Neil Greenspan, and Dr. Laurence C. Eisenlohr.

The Inductive Method of Teaching Visual Art Criticism.

Science.gov (United States)

Clements, Robert D.

1979-01-01

The author describes how the true principles of the scientific inductive method are not opposed to the principles of teaching visual art criticism, and suggests that the inductive method of teaching visual art criticism strips it of its mystique in order to make clear its vital role in intellectual development. (KC)

Drowning stars: reassessing the role of astrocytes in brain edema.

Science.gov (United States)

Thrane, Alexander S; Rangroo Thrane, Vinita; Nedergaard, Maiken

2014-11-01

Edema formation frequently complicates brain infarction, tumors, and trauma. Despite the significant mortality of this condition, current treatment options are often ineffective or incompletely understood. Recent studies have revealed the existence of a brain-wide paravascular pathway for cerebrospinal (CSF) and interstitial fluid (ISF) exchange. The current review critically examines the contribution of this 'glymphatic' system to the main types of brain edema. We propose that in cytotoxic edema, energy depletion enhances glymphatic CSF influx, whilst suppressing ISF efflux. We also argue that paravascular inflammation or 'paravasculitis' plays a critical role in vasogenic edema. Finally, recent advances in diagnostic imaging of glymphatic function may hold the key to defining the edema profile of individual patients, and thus enable more targeted therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

A critical role for Arabidopsis MILDEW RESISTANCE LOCUS O2 in systemic acquired resistance.

Science.gov (United States)

Gruner, Katrin; Zeier, Tatyana; Aretz, Christina; Zeier, Jürgen

2018-04-16

Members of the MILDEW RESISTANCE LOCUS O (MLO) gene family confer susceptibility to powdery mildews in different plant species, and their existence therefore seems to be disadvantageous for the plant. We recognized that expression of the Arabidopsis MLO2 gene is induced after inoculation with the bacterial pathogen Pseudomonas syringae, promoted by salicylic acid (SA) signaling, and systemically enhanced in the foliage of plants exhibiting systemic acquired resistance (SAR). Importantly, distinct mlo2 mutant lines were unable to systemically increase resistance to bacterial infection after inoculation with P. syringae, indicating that the function of MLO2 is necessary for biologically-induced SAR in Arabidopsis. Our data also suggest that the close homolog MLO6 has a supportive but less critical role in SAR. In contrast to SAR, basal resistance to bacterial infection was not affected in mlo2. Remarkably, SAR-defective mlo2 mutants were still competent in systemically increasing the levels of the SAR-activating metabolites pipecolic acid (Pip) and SA after inoculation, and to enhance SAR-related gene expression in distal plant parts. Furthermore, although MLO2 was not required for SA- or Pip-inducible defense gene expression, it was essential for the proper induction of disease resistance by both SAR signals. We conclude that MLO2 acts as a critical downstream component in the execution of SAR to bacterial infection, being required for the translation of elevated defense responses into disease resistance. Moreover, our data suggest a function for MLO2 in the activation of plant defense priming during a P. syringae challenge. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Role-meanings as a critical factor in understanding doctor managers' identity work and different role identities.

Science.gov (United States)

Cascón-Pereira, Rosalía; Chillas, Shiona; Hallier, Jerry

2016-12-01

This study examines "identity work" among hybrid doctor-managers (DMs) in the Spanish National Health System to make sense of their managerial roles. In particular, the meanings underlying DMs experience of their hybrid role are investigated using a Grounded Theory methodology, exposing distinctions in role-meanings. Our findings provide evidence that using different social sources of comparison (senior managers or clinicians) to construct the meaning of managerial roles leads to different role-meanings and role identities, which are the source of the two established types of DM in the literature, the reluctant and the enthusiast. The contribution is twofold: our findings lead us to theorize DMs' identity work processes by adding an overlooked role-meaning dimension to identity work; and raise practical reflections for those who wish to develop enthusiast doctor managers. Copyright © 2016 Elsevier Ltd. All rights reserved.

In trans complementation of lethal factor reveal roles in colonization and dissemination in a murine mouse model.

Directory of Open Access Journals (Sweden)

David E Lowe

Full Text Available Lethal factor (LF is a component of the B. anthracis exotoxin and critical for pathogenesis. The roles of LF in early anthrax pathogenesis, such as colonization and dissemination from the initial site of infection, are poorly understood. In mice models of infection, LF-deficient strains either have altered dissemination patterns or do not colonize, precluding analysis of the role of LF in colonization and dissemination from the portal of entry. Previous reports indicate rabbit and guinea pig models infected with LF-deficient strains have decreased virulence, yet the inability to use bioluminescent imaging techniques to track B. anthracis growth and dissemination in these hosts makes analysis of early pathogenesis challenging. In this study, the roles of LF early in infection were analyzed using bioluminescent signature tagged libraries of B. anthracis with varying ratios of LF-producing and LF-deficient clones. Populations where all clones produced LF and populations where only 40% of clones produce LF were equally virulent. The 40% LF-producing clones trans complimented the LF mutants and permitted them to colonize and disseminate. Decreases of the LF producing strains to 10% or 0.3% of the population led to increased host survival and decreased trans complementation of the LF mutants. A library with 10% LF producing clones could replicate and disseminate, but fewer clones disseminated and the mutant clones were less competitive than wild type. The inoculum with 0.3% LF producing clones could not colonize the host. This strongly suggests that between 10% and 0.3% of the population must produce LF in order to colonize. In total, these findings suggest that a threshold of LF must be produced in order for colonization and dissemination to occur in vivo. These observations suggest that LF has a major role in the early stages of colonization and dissemination.

Action simulation plays a critical role in deceptive action recognition.

Science.gov (United States)

Tidoni, Emmanuele; Borgomaneri, Sara; di Pellegrino, Giuseppe; Avenanti, Alessio

2013-01-09

The ability to infer deceptive intents from nonverbal behavior is critical for social interactions. By combining single-pulse and repetitive transcranial magnetic stimulation (TMS) in healthy humans, we provide both correlational and causative evidence that action simulation is actively involved in the ability to recognize deceptive body movements. We recorded motor-evoked potentials during a faked-action discrimination (FAD) task: participants watched videos of actors lifting a cube and judged whether the actors were trying to deceive them concerning the real weight of the cube. Seeing faked actions facilitated the observers' motor system more than truthful actions in a body-part-specific manner, suggesting that motor resonance was sensitive to deceptive movements. Furthermore, we found that TMS virtual lesion to the anterior node of the action observation network, namely the left inferior frontal cortex (IFC), reduced perceptual sensitivity in the FAD task. In contrast, no change in FAD task performance was found after virtual lesions to the left temporoparietal junction (control site). Moreover, virtual lesion to the IFC failed to affect performance in a difficulty-matched spatial-control task that did not require processing of spatiotemporal (acceleration) and configurational (limb displacement) features of seen actions, which are critical to detecting deceptive intent in the actions of others. These findings indicate that the human IFC is critical for recognizing deceptive body movements and suggest that FAD relies on the simulation of subtle changes in action kinematics within the motor system.

Detecting critical illness outside the ICU: the role of track and trigger systems.

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Jansen, Jan O; Cuthbertson, Brian H

2010-06-01

Critical illness is often preceded by physiological deterioration. Track and trigger systems are intended to facilitate the timely recognition of patients with potential or established critical illness outside critical care areas. The aim of this article is to review the evidence for the use of such systems. Existing track and trigger systems have low sensitivity, low positive predictive values, and high specificity. They often fail to identify patients who need additional care and have not been shown to improve outcomes. The development of such systems must be based on robust methodological and statistical principles. At present, few track and trigger systems meet these standards. Although track and trigger systems, combined with appropriate response algorithms, have the potential to improve the recognition and management of critical illness, further work is required to validate their utility.

Roles of PDE1 in Pathological Cardiac Remodeling and Dysfunction.

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Chen, Si; Knight, Walter E; Yan, Chen

2018-04-23

Pathological cardiac hypertrophy and dysfunction is a response to various stress stimuli and can result in reduced cardiac output and heart failure. Cyclic nucleotide signaling regulates several cardiac functions including contractility, remodeling, and fibrosis. Cyclic nucleotide phosphodiesterases (PDEs), by catalyzing the hydrolysis of cyclic nucleotides, are critical in the homeostasis of intracellular cyclic nucleotide signaling and hold great therapeutic potential as drug targets. Recent studies have revealed that the inhibition of the PDE family member PDE1 plays a protective role in pathological cardiac remodeling and dysfunction by the modulation of distinct cyclic nucleotide signaling pathways. This review summarizes recent key findings regarding the roles of PDE1 in the cardiac system that can lead to a better understanding of its therapeutic potential.

Critical Role of Airway Macrophages in Modulating Disease Severity during Influenza Virus Infection of Mice ▿

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Tate, Michelle D.; Pickett, Danielle L.; van Rooijen, Nico; Brooks, Andrew G.; Reading, Patrick C.

2010-01-01

Airway macrophages provide a first line of host defense against a range of airborne pathogens, including influenza virus. In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus strain PR8 (H1N1) was poor in its ability to infect macrophages and highly virulent for mice. Depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in BJx109-infected mice but did not modulate disease severity in PR8-infected mice. The severe disease observed in macrophage-depleted mice infected with BJx109 was associated with exacerbated virus replication in the airways, leading to severe airway inflammation, pulmonary edema, and vascular leakage, indicative of lung injury. Thymic atrophy, lymphopenia, and dysregulated cytokine and chemokine production were additional systemic manifestations associated with severe disease. Thus, airway macrophages play a critical role in limiting lung injury and associated disease caused by BJx109. Furthermore, the inability of PR8 to infect airway macrophages may be a critical factor contributing to its virulence for mice. PMID:20504924

Critical feature analysis of a radiotherapy machine

International Nuclear Information System (INIS)

Rae, Andrew; Jackson, Daniel; Ramanan, Prasad; Flanz, Jay; Leyman, Didier

2005-01-01

The software implementation of the emergency shutdown feature in a major radiotherapy system was analyzed, using a directed form of code review based on module dependences. Dependences between modules are labelled by particular assumptions; this allows one to trace through the code, and identify those fragments responsible for critical features. An 'assumption tree' is constructed in parallel, showing the assumptions which each module makes about others. The root of the assumption tree is the critical feature of interest, and its leaves represent assumptions which, if not valid, might cause the critical feature to fail. The analysis revealed some unexpected assumptions that motivated improvements to the code

Soil water stable isotopes reveal evaporation dynamics at the soil–plant–atmosphere interface of the critical zone

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M. Sprenger

2017-07-01

Full Text Available Understanding the influence of vegetation on water storage and flux in the upper soil is crucial in assessing the consequences of climate and land use change. We sampled the upper 20 cm of podzolic soils at 5 cm intervals in four sites differing in their vegetation (Scots Pine (Pinus sylvestris and heather (Calluna sp. and Erica Sp and aspect. The sites were located within the Bruntland Burn long-term experimental catchment in the Scottish Highlands, a low energy, wet environment. Sampling took place on 11 occasions between September 2015 and September 2016 to capture seasonal variability in isotope dynamics. The pore waters of soil samples were analyzed for their isotopic composition (δ2H and δ18O with the direct-equilibration method. Our results show that the soil waters in the top soil are, despite the low potential evaporation rates in such northern latitudes, kinetically fractionated compared to the precipitation input throughout the year. This fractionation signal decreases within the upper 15 cm resulting in the top 5 cm being isotopically differentiated to the soil at 15–20 cm soil depth. There are significant differences in the fractionation signal between soils beneath heather and soils beneath Scots pine, with the latter being more pronounced. But again, this difference diminishes within the upper 15 cm of soil. The enrichment in heavy isotopes in the topsoil follows a seasonal hysteresis pattern, indicating a lag time between the fractionation signal in the soil and the increase/decrease of soil evaporation in spring/autumn. Based on the kinetic enrichment of the soil water isotopes, we estimated the soil evaporation losses to be about 5 and 10 % of the infiltrating water for soils beneath heather and Scots pine, respectively. The high sampling frequency in time (monthly and depth (5 cm intervals revealed high temporal and spatial variability of the isotopic composition of soil waters, which can be critical

The critical role of catalase in prooxidant and antioxidant function of p53

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Kang, M Y; Kim, H-B; Piao, C; Lee, K H; Hyun, J W; Chang, I-Y; You, H J

2013-01-01

The tumor suppressor p53 is an important regulator of intracellular reactive oxygen species (ROS) levels, although downstream mediators of p53 remain to be elucidated. Here, we show that p53 and its downstream targets, p53-inducible ribonucleotide reductase (p53R2) and p53-inducible gene 3 (PIG3), physically and functionally interact with catalase for efficient regulation of intracellular ROS, depending on stress intensity. Under physiological conditions, the antioxidant functions of p53 are mediated by p53R2, which maintains increased catalase activity and thereby protects against endogenous ROS. After genotoxic stress, high levels of p53 and PIG3 cooperate to inhibit catalase activity, leading to a shift in the oxidant/antioxidant balance toward an oxidative status, which could augment apoptotic cell death. These results highlight the essential role of catalase in p53-mediated ROS regulation and suggest that the p53/p53R2–catalase and p53/PIG3–catalase pathways are critically involved in intracellular ROS regulation under physiological conditions and during the response to DNA damage, respectively. PMID:22918438

Critical role of acrolein in secondary injury following ex vivo spinal cord trauma.

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Hamann, Kristin; Durkes, Abigail; Ouyang, Hui; Uchida, Koji; Pond, Amber; Shi, Riyi

2008-11-01

The pathophysiology of spinal cord injury (SCI) is characterized by the initial, primary injury followed by secondary injury processes in which oxidative stress is a critical component. Secondary injury processes not only exacerbate pathology at the site of primary injury, but also result in spreading of injuries to the adjacent, otherwise healthy tissue. The lipid peroxidation byproduct acrolein has been implicated as one potential mediator of secondary injury. To further and rigorously elucidate the role of acrolein in secondary injury, a unique ex vivo model is utilized to isolate the detrimental effects of mechanical injury from toxins such as acrolein that are produced endogenously following SCI. We demonstrate that (i) acrolein-Lys adducts are capable of diffusing from compressed tissue to adjacent, otherwise uninjured tissue; (ii) secondary injury by itself produces significant membrane damage and increased superoxide production; and (iii) these injuries are significantly attenuated by the acrolein scavenger hydralazine. Furthermore, hydralazine treatment results in significantly less membrane damage 2 h following compression injury, but not immediately after. These findings support our hypothesis that, following SCI, acrolein is increased to pathologic concentrations, contributes significantly to secondary injury, and thus represents a novel target for scavenging to promote improved recovery.

Towards a critical theory of information

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Christian Fuchs

2009-11-01

The debate on redistribution and recognition between critical theorists Nancy Fraser and Axel Honneth gives the opportunity to renew the discussion of the relationship of base and superstructure in critical social theory. Critical information theory needs to be aware of economic, political, and cultural demands that it needs to make in struggles for ending domination and oppression, and of the unifying role that the economy and class play in these demands and struggles. Objective and subjective information concepts are based on the underlying worldview of reification. Reification endangers human existence. Information as process and relation enables political and ethical alternatives that have radical implications for society.

Receptor homodimerization plays a critical role in a novel dominant negative P2RY12 variant identified in a family with severe bleeding.

Science.gov (United States)

Mundell, S J; Rabbolini, D; Gabrielli, S; Chen, Q; Aungraheeta, R; Hutchinson, J L; Kilo, T; Mackay, J; Ward, C M; Stevenson, W; Morel-Kopp, M-C

2018-01-01

Essentials Three dominant variants for the autosomal recessive bleeding disorder type-8 have been described. To date, there has been no phenotype/genotype correlation explaining their dominant transmission. Proline plays an important role in P2Y12R ligand binding and signaling defects. P2Y12R homodimer formation is critical for the receptor function and signaling. Background Although inherited platelet disorders are still underdiagnosed worldwide, advances in molecular techniques are improving disease diagnosis and patient management. Objective To identify and characterize the mechanism underlying the bleeding phenotype in a Caucasian family with an autosomal dominant P2RY12 variant. Methods Full blood counts, platelet aggregometry, flow cytometry and western blotting were performed before next-generation sequencing (NGS). Detailed molecular analysis of the identified variant of the P2Y12 receptor (P2Y12R) was subsequently performed in mammalian cells overexpressing receptor constructs. Results All three referred individuals had markedly impaired ADP-induced platelet aggregation with primary wave only, despite normal total and surface P2Y12R expression. By NGS, a single P2RY12:c.G794C substitution (p.R265P) was identified in all affected individuals, and this was confirmed by Sanger sequencing. Mammalian cell experiments with the R265P-P2Y12R variant showed normal receptor surface expression versus wild-type (WT) P2Y12R. Agonist-stimulated R265P-P2Y12R function (both signaling and surface receptor loss) was reduced versus WT P2Y12R. Critically, R265P-P2Y12R acted in a dominant negative manner, with agonist-stimulated WT P2Y12R activity being reduced by variant coexpression, suggesting dramatic loss of WT homodimers. Importantly, platelet P2RY12 cDNA cloning and sequencing in two affected individuals also revealed three-fold mutant mRNA overexpression, decreasing even further the likelihood of WT homodimer formation. R265 located within extracellular loop 3 (EL3) is

Multidisciplinary evaluation of an emergency department nurse navigator role: A mixed methods study.

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Jessup, Melanie; Fulbrook, Paul; Kinnear, Frances B

2017-09-20

To utilise multidisciplinary staff feedback to assess their perceptions of a novel emergency department nurse navigator role and to understand the impact of the role on the department. Prolonged emergency department stays impact patients, staff and quality of care, and are linked to increased morbidity and mortality. One innovative strategy to facilitate patient flow is the navigator: a nurse supporting staff in care delivery to enhance efficient, timely movement of patients through the department. However, there is a lack of rigorous research into this emerging role. Sequential exploratory mixed methods. A supernumerary emergency department nurse navigator was implemented week-off-week-on, seven days a week for 20 weeks. Diaries, focus groups, and an online survey (24-item Navigator Role Evaluation tool) were used to collect and synthesise data from the perspectives of multidisciplinary departmental staff. Thematic content analysis of cumulative qualitative data drawn from the navigators' diaries, focus groups and survey revealed iterative processes of the navigators growing into the role and staff incorporating the role into departmental flow, manifested as: Reception of the role and relationships with staff; Defining the role; and Assimilation of the role. Statistical analysis of survey data revealed overall staff satisfaction with the role. Physicians, nurses and others assessed it similarly. However, only 44% felt the role was an overall success, less than half (44%) considered it necessary, and just over a third (38%) thought it positively impacted inter-professional relationships. Investigation of individual items revealed several areas of uncertainty about the role. Within-group differences between nursing grades were noted, junior nurses rating the role significantly higher than more senior nurses. Staff input yielded invaluable insider feedback for ensuing modification and optimal instigation of the navigator role, rendering a sense of departmental

Action Simulation Plays a Critical Role in Deceptive Action Recognition

NARCIS (Netherlands)

Tidoni, Emmanuele; Borgomaneri, Sara; Di Pellegrino, Giuseppe; Avenanti, Alessio

2013-01-01

The ability to infer deceptive intents from nonverbal behavior is critical for social interactions. By combining single-pulse and repetitive transcranial magnetic stimulation (TMS) in healthy humans, we provide both correlational and causative evidence that action simulation is actively involved in

Genetic activation, inactivation and deletion reveal a limited and nuanced role for somatostatin-containing basal forebrain neurons in behavioral state control.

Science.gov (United States)

Anaclet, Christelle; De Luca, Roberto; Venner, Anne; Malyshevskaya, Olga; Lazarus, Michael; Arrigoni, Elda; Fuller, Patrick M

2018-05-07

Recent studies have identified an especially important role for basal forebrain GABAergic (BF VGAT ) neurons in the regulation of behavioral waking and fast cortical rhythms associated with cognition. However, BF VGAT neurons comprise several neurochemically and anatomically distinct sub-populations, including parvalbumin- and somatostatin-containing BF VGAT neurons (BF Parv and BF SOM ), and it was recently reported that optogenetic activation of BF SOM neurons increases the probability of a wakefulness to non-rapid-eye movement (NREM) sleep transition when stimulated during the animal's rest period. This finding was unexpected given that most BF SOM neurons are not NREM sleep active and that central administration of the synthetic SOM analog, octreotide, suppresses NREM sleep or increases REM sleep. Here we employed a combination of genetically-driven chemogenetic and optogenetic activation, chemogenetic inhibition and ablation approaches to further explore the in vivo role of BF SOM neurons in arousal control. Our findings indicate that acute activation or inhibition of BF SOM neurons is neither wakefulness- nor NREM sleep-promoting, is without significant effect on the EEG, and that chronic loss of these neurons is without effect on total 24h sleep amounts, although a small but significant increase in waking was observed in the lesioned mice during the early active period. Our in vitro cell recordings further reveal electrophysiological heterogeneity in BF SOM neurons, specifically suggesting at least two distinct sub-populations. Taken together our data support the more nuanced view that BF SOM are electrically heterogeneous and are not NREM sleep- or wake-promoting per se , but may exert, in particular during the early active period, a modest inhibitory influence on arousal circuitry. SIGNIFICANCE STATEMENT The cellular basal forebrain (BF) is a highly complex area of the brain that is implicated in a wide-range of higher-level neurobiological processes

Advanced practice nursing role delineation in acute and critical care: application of the strong model of advanced practice.

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Mick, D J; Ackerman, M H

2000-01-01

This purpose of this study was to differentiate between the roles of clinical nurse specialists and acute care nurse practitioners. Hypothesized blending of the clinical nurse specialist and acute care nurse practitioner roles is thought to result in an acute care clinician who integrates the clinical skills of the nurse practitioner with the systems knowledge, educational commitment, and leadership ability of the clinical nurse specialist. Ideally, this role blending would facilitate excellence in both direct and indirect patient care. The Strong Model of Advanced Practice, which incorporates practice domains of direct comprehensive care, support of systems, education, research, and publication and professional leadership, was tested to search for practical evidence of role blending. This descriptive, exploratory, pilot study included subjects (N = 18) solicited from an academic medical center and from an Internet advanced practice listserv. Questionnaires included self-ranking of expertise in practice domains, as well as valuing of role-related tasks. Content validity was judged by an expert panel of advanced practice nurses. Analyses of descriptive statistics revealed that clinical nurse specialists, who had more experience both as registered nurses and in the advanced practice nurse role, self-ranked their expertise higher in all practice domains. Acute care nurse practitioners placed higher importance on tasks related to direct comprehensive care, including conducting histories and physicals, diagnosing, and performing diagnostic procedures, whereas clinical nurse specialists assigned greater importance to tasks related to education, research, and leadership. Levels of self-assessed clinical expertise as well as valuing of role-related tasks differed among this sample of clinical nurse specialists and acute care nurse practitioners. Groundwork has been laid for continuing exploration into differentiation in advanced practice nursing roles. As the clinical

Role of interatomic bonding in the mechanical anisotropy and interlayer cohesion of CSH crystals

Energy Technology Data Exchange (ETDEWEB)

Dharmawardhana, C.C. [Department of Physics and Astronomy, University of Missouri—Kansas City, Kansas City, MO 64110 (United States); Misra, A. [Department of Civil, Environmental, and Architectural Engineering, University of Kansas, Lawrence, KS 66045 (United States); Aryal, S.; Rulis, P. [Department of Physics and Astronomy, University of Missouri—Kansas City, Kansas City, MO 64110 (United States); Ching, W.Y., E-mail: ccdxz8@mail.umkc.edu [Department of Physics and Astronomy, University of Missouri—Kansas City, Kansas City, MO 64110 (United States)

2013-10-15

Atomic scale properties of calcium silicate hydrate (CSH), the main binding phase of hardened Portland cement, are not well understood. Over a century of intense research has identified almost 50 different crystalline CSH minerals which are mainly categorized by their Ca/Si ratio. The electronic structure and interatomic bonding in four major CSH crystalline phases with structures close to those found in hardened cement are investigated via ab initio methods. Our result reveals the critical role of hydrogen bonding and importance of specifying precise locations for water molecules. Quantitative analysis of contributions from different bond types to the overall cohesion shows that while the Si-O covalent bonds dominate, the hydrogen bonding and Ca-O bonding are also very significant. Calculated results reveal the correlation between bond topology and interlayer cohesion. The overall bond order density (BOD) is found to be a more critical measure than the Ca/Si ratio in classifying different CSH crystals.

Examining portrayals of female protagonists by female screenwriters using feminist critical discourse analysis.

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Shapiro, B.

2017-07-01

Full Text Available This study explores the portrayals of female protagonists by female screenwriters through feminist critical discourse analysis. Specifically, this study examines the female protagonists in the four Academy-Award winning films Thelma & Louise, The Piano, Lost in Translation, and Juno. By analyzing the roles and behavior of the female protagonists in these four films, I reveal how these female protagonists each experience the Heroine’s Journey, where they transcend their gender constraints and become more independent and empowered. These portrayals by female screenwriters are vital to the off-screen sector of the film industry because of the Social Cognitive Theory of Gender Development and Differentiation, which states that human beings gain knowledge from the messages communicated to them by the media. Therefore, I conclude that the existing gap between female and male screenwriters must be closed to counter the reinforcement of gender roles and stereotypes, as well as ensure that women are inspired, not discouraged, by what they see on screen.

A Systems Approach Reveals MAVS Signaling in Myeloid Cells as Critical for Resistance to Ebola Virus in Murine Models of Infection

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Mukta Dutta

2017-01-01

Full Text Available The unprecedented 2013–2016 outbreak of Ebola virus (EBOV resulted in over 11,300 human deaths. Host resistance to RNA viruses requires RIG-I-like receptor (RLR signaling through the adaptor protein, mitochondrial antiviral signaling protein (MAVS, but the role of RLR-MAVS in orchestrating anti-EBOV responses in vivo is not known. Here we apply a systems approach to MAVS−/− mice infected with either wild-type or mouse-adapted EBOV. MAVS controlled EBOV replication through the expression of IFNα, regulation of inflammatory responses in the spleen, and prevention of cell death in the liver, with macrophages implicated as a major cell type influencing host resistance. A dominant role for RLR signaling in macrophages was confirmed following conditional MAVS deletion in LysM+ myeloid cells. These findings reveal tissue-specific MAVS-dependent transcriptional pathways associated with resistance to EBOV, and they demonstrate that EBOV adaptation to cause disease in mice involves changes in two distinct events, RLR-MAVS antagonism and suppression of RLR-independent IFN-I responses.

A Systems Approach Reveals MAVS Signaling in Myeloid Cells as Critical for Resistance to Ebola Virus in Murine Models of Infection.

Science.gov (United States)

Dutta, Mukta; Robertson, Shelly J; Okumura, Atsushi; Scott, Dana P; Chang, Jean; Weiss, Jeffrey M; Sturdevant, Gail L; Feldmann, Friederike; Haddock, Elaine; Chiramel, Abhilash I; Ponia, Sanket S; Dougherty, Jonathan D; Katze, Michael G; Rasmussen, Angela L; Best, Sonja M

2017-01-17

The unprecedented 2013-2016 outbreak of Ebola virus (EBOV) resulted in over 11,300 human deaths. Host resistance to RNA viruses requires RIG-I-like receptor (RLR) signaling through the adaptor protein, mitochondrial antiviral signaling protein (MAVS), but the role of RLR-MAVS in orchestrating anti-EBOV responses in vivo is not known. Here we apply a systems approach to MAVS -/- mice infected with either wild-type or mouse-adapted EBOV. MAVS controlled EBOV replication through the expression of IFNα, regulation of inflammatory responses in the spleen, and prevention of cell death in the liver, with macrophages implicated as a major cell type influencing host resistance. A dominant role for RLR signaling in macrophages was confirmed following conditional MAVS deletion in LysM+ myeloid cells. These findings reveal tissue-specific MAVS-dependent transcriptional pathways associated with resistance to EBOV, and they demonstrate that EBOV adaptation to cause disease in mice involves changes in two distinct events, RLR-MAVS antagonism and suppression of RLR-independent IFN-I responses. Published by Elsevier Inc.

The relationship between family expressed emotion, perceived criticism and criticism sensitivity and psychiatric outcomes following traumatic brain injury.

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Alway, Yvette; Ponsford, Jennie; McKay, Adam

2016-12-30

Family expressed emotion (EE) is a strong predictor of outcome in a range of psychiatric and medical conditions. This study aimed to examine the relationship between family EE-criticism, patient perceived criticism and criticism sensitivity and psychiatric disorders following moderate to severe traumatic brain injury (TBI). Participants were 60 patients with TBI and their family members. Patients were assessed for psychiatric disorders using the Structured Clinical Interview for DSM-IV (SCID-I) and completed the Perceived Criticism Measure (PCM) to determine levels of perceived criticism and criticism sensitivity. Family members completed the Family Questionnaire (FQ) to assess patient directed EE-criticism. Patients were reassessed approximately 12-months post-baseline. After controlling for diagnostic status at baseline, high criticism sensitivity at baseline was associated with greater probability of psychiatric diagnosis at follow-up (odds ratio=3.99, 95% CI=1.15-13.71). Family EE-criticism and perceived criticism were not predictive of patient diagnostic status at follow-up, but patients with high EE-family members were more likely to have a concurrent psychiatric diagnosis at baseline. Findings suggest that sensitivity to interpersonal criticism may have a role in the development and course of psychiatric disorders following TBI. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Role of computers in quality assurance in the LLL Criticality Safety Program

International Nuclear Information System (INIS)

Koponen, B.L.

1978-01-01

Some of the aspects of computational criticality safety quality assurance that have been emphasized in recent years at LLL are summarized. In particular, computer code changes that have been made that help the criticality analyst reduce the number of errors that he makes and to locate those that he does make; and how a computerized ''benchmark'' data base aids him in the validation of his computational methods are discussed

Superconductivity versus quantum criticality: Effects of thermal fluctuations

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Wang, Huajia; Wang, Yuxuan; Torroba, Gonzalo

2018-02-01

We study the interplay between superconductivity and non-Fermi liquid behavior of a Fermi surface coupled to a massless SU(N ) matrix boson near the quantum critical point. The presence of thermal infrared singularities in both the fermionic self-energy and the gap equation invalidates the Eliashberg approximation, and makes the quantum-critical pairing problem qualitatively different from that at zero temperature. Taking the large N limit, we solve the gap equation beyond the Eliashberg approximation, and obtain the superconducting temperature Tc as a function of N . Our results show an anomalous scaling between the zero-temperature gap and Tc. For N greater than a critical value, we find that Tc vanishes with a Berezinskii-Kosterlitz-Thouless scaling behavior, and the system retains non-Fermi liquid behavior down to zero temperature. This confirms and extends previous renormalization-group analyses done at T =0 , and provides a controlled example of a naked quantum critical point. We discuss the crucial role of thermal fluctuations in relating our results with earlier work where superconductivity always develops due to the special role of the first Matsubara frequency.

Critical role for thymic CD19+CD5+CD1dhiIL-10+ regulatory B cells in immune homeostasis.

Science.gov (United States)

Xing, Chen; Ma, Ning; Xiao, He; Wang, Xiaoqian; Zheng, Mingke; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Shen, Beifen; Li, Yan; Wang, Renxi

2015-03-01

This study tested the hypothesis that besides the spleen, LNs, peripheral blood, and thymus contain a regulatory IL-10-producing CD19(+)CD5(+)CD1d(high) B cell subset that may play a critical role in the maintenance of immune homeostasis. Indeed, this population was identified in the murine thymus, and furthermore, when cocultured with CD4(+) T cells, this population of B cells supported the maintenance of CD4(+)Foxp3(+) Tregs in vitro, in part, via the CD5-CD72 interaction. Mice homozygous for Cd19(Cre) (CD19(-/-)) express B cells with impaired signaling and humoral responses. Strikingly, CD19(-/-) mice produce fewer CD4(+)Foxp3(+) Tregs and a greater percentage of CD4(+)CD8(-) and CD4(-)CD8(+) T cells. Consistent with these results, transfer of thymic CD19(+)CD5(+)CD1d(hi) B cells into CD19(-/-) mice resulted in significantly up-regulated numbers of CD4(+)Foxp3(+) Tregs with a concomitant reduction in CD4(+)CD8(-) and CD4(-)CD8(+) T cell populations in the thymus, spleen, and LNs but not in the BM of recipient mice. In addition, thymic CD19(+)CD5(+)CD1d(hi) B cells significantly suppressed autoimmune responses in lupus-like mice via up-regulation of CD4(+)Foxp3(+) Tregs and IL-10-producing Bregs. This study suggests that thymic CD19(+)CD5(+)CD1d(hi)IL-10(+) Bregs play a critical role in the maintenance of immune homeostasis. © Society for Leukocyte Biology.

The impact of social roles on trait judgments: a critical reexamination.

Science.gov (United States)

Bosak, Janine; Sczesny, Sabine; Eagly, Alice H

2012-04-01

Consistent with social role theory's assumption that the role behavior of men and women shapes gender stereotypes, earlier experiments have found that men's and women's occupancy of the same role eliminated gender-stereotypical judgments of greater agency and lower communion in men than women. The shifting standards model raises the question of whether a shift to within-sex standards in judgments of men and women in roles could have masked underlying gender stereotypes. To examine this possibility, two experiments obtained judgments of men and women using measures that do or do not restrain shifts to within-sex standards. This measure variation did not affect the social role pattern of smaller perceived sex differences in the presence of role information. These findings thus support the social role theory claim that designations of identical roles for subgroups of men and women eliminate or reduce perceived sex differences.

The NLRP3 Inflammasome Has a Critical Role in Peritoneal Dialysis-Related Peritonitis.

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Hautem, Nicolas; Morelle, Johann; Sow, Amadou; Corbet, Cyril; Feron, Olivier; Goffin, Eric; Huaux, François; Devuyst, Olivier

2017-07-01

Bacterial peritonitis remains the main cause of technique failure in peritoneal dialysis (PD). During peritonitis, the peritoneal membrane undergoes structural and functional alterations that are mediated by IL-1 β The NLRP3 inflammasome is a caspase-1-activating multiprotein complex that links sensing of microbial and stress products to activation of proinflammatory cytokines, including IL-1 β The potential roles of the NLRP3 inflammasome and IL-1 β in the peritoneal membrane during acute peritonitis have not been investigated. Here, we show that the NLRP3 inflammasome is activated during acute bacterial peritonitis in patients on PD, and this activation associates with the release of IL-1 β in the dialysate. In mice, lipopolysaccharide- or Escherichia coli -induced peritonitis led to IL-1 β release in the peritoneal membrane. The genetic deletion of Nalp3 , which encodes NLRP3, abrogated defects in solute transport during acute peritonitis and restored ultrafiltration. In human umbilical vein endothelial cells, IL-1 β treatment directly enhanced endothelial cell proliferation and increased microvascular permeability. These in vitro effects require endothelial IL-1 receptors, shown by immunofluorescence to be expressed in peritoneal capillaries in mice. Furthermore, administration of the IL-1 β receptor antagonist, anakinra, efficiently decreased nitric oxide production and vascular proliferation and restored peritoneal function in mouse models of peritonitis, even in mice treated with standard-of-care antibiotherapy. These data demonstrate that NLRP3 activation and IL-1 β release have a critical role in solute transport defects and tissue remodeling during PD-related peritonitis. Blockade of the NLRP3/IL-1 β axis offers a novel method for rescuing morphologic alterations and transport defects during acute peritonitis. Copyright © 2017 by the American Society of Nephrology.

When proteomics reveals unsuspected roles: the plastoglobule example

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Claire eBréhélin

2013-04-01

Full Text Available Plastoglobules are globular compartments found in plastids. Before initial proteomic studies were published, these particles were often viewed as passive lipid droplets whose unique role was to store lipids coming from the thylakoid turn-over, or to accumulate carotenoids in the chromoplasts. Yet, two proteomic studies, published concomitantly, suggested for the first time that plastoglobules are more than "junk cupboards" for lipids. Indeed, both studies demonstrated that plastoglobules do not only include structural proteins belonging to the plastoglobulin / fibrillin family, but also contain active enzymes. The specific plastoglobule localization of these enzymes has been confirmed by different approaches such as immunogold localization and GFP protein fusions, thus providing evidence that plastoglobules actively participate in diverse pathways of plastid metabolism. These proteomic studies have been the basis for numerous recent works investigating plastoglobule function. However, a lot still needs to be discovered about the molecular composition and the role of plastoglobules. In this chapter, we will describe how the proteomic approaches have launched new perspectives on plastoglobule functions.

The Role and Impact of Critical Review as Perceived by an Implementer

International Nuclear Information System (INIS)

Thegerstroem, Claes; Laarouchi Engstroem, Saida; Olsson, Olle

2006-01-01

The quality and success of a nuclear waste management programme is based on the amalgamation of the interests of a wide number of stakeholders, integration of many different scientific disciplines, and merging of scientific, technical, ethical and social issues. In this process, a broad and structured review of all aspects of the program is necessary and we find the process with submission and review by stakeholders, regulators and government every third year very useful. High-quality critical review of is always a real benefit to the implementer - as it gives the implementer the possibility to see where improvements can be made. However, a close dialogue and a dynamic reviewing process, where questions are raised throughout the process, are essential in order to optimize the quality of the final applications. Naturally, critical review should not be used for pushing specific general research interests or issues that belong to the political arena rather than nuclear waste management itself. Moreover, critical review provides additional insight and promotes confidence by the general public. However, sometimes the public might be confused and have difficulties in judging the importance and relevance of critical comments. The implementer and regulatory authorities have a special duty to provide an overall perspective of safety-related issues. Even if critical review is valuable, the implementer can not only rely on this. The implementers' own internal quality assurance practise, internal review process as well as its overall safety culture is all crucial. Indeed, a successful management of radio-active waste, including operational aspects as well as siting process, starts with the implementers' own wish to perform state-of-the art-work both in terms of technology and overall approach

The Role and Impact of Critical Review as Perceived by an Implementer

Energy Technology Data Exchange (ETDEWEB)

Thegerstroem, Claes; Laarouchi Engstroem, Saida; Olsson, Olle [Swedish Nuclear Fuel and Waste Management Co, Stockholm (Sweden)

2006-09-15

The quality and success of a nuclear waste management programme is based on the amalgamation of the interests of a wide number of stakeholders, integration of many different scientific disciplines, and merging of scientific, technical, ethical and social issues. In this process, a broad and structured review of all aspects of the program is necessary and we find the process with submission and review by stakeholders, regulators and government every third year very useful. High-quality critical review of is always a real benefit to the implementer - as it gives the implementer the possibility to see where improvements can be made. However, a close dialogue and a dynamic reviewing process, where questions are raised throughout the process, are essential in order to optimize the quality of the final applications. Naturally, critical review should not be used for pushing specific general research interests or issues that belong to the political arena rather than nuclear waste management itself. Moreover, critical review provides additional insight and promotes confidence by the general public. However, sometimes the public might be confused and have difficulties in judging the importance and relevance of critical comments. The implementer and regulatory authorities have a special duty to provide an overall perspective of safety-related issues. Even if critical review is valuable, the implementer can not only rely on this. The implementers' own internal quality assurance practise, internal review process as well as its overall safety culture is all crucial. Indeed, a successful management of radio-active waste, including operational aspects as well as siting process, starts with the implementers' own wish to perform state-of-the art-work both in terms of technology and overall approach.

Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis.

Science.gov (United States)

Annibali, Daniela; Whitfield, Jonathan R; Favuzzi, Emilia; Jauset, Toni; Serrano, Erika; Cuartas, Isabel; Redondo-Campos, Sara; Folch, Gerard; Gonzàlez-Juncà, Alba; Sodir, Nicole M; Massó-Vallés, Daniel; Beaulieu, Marie-Eve; Swigart, Lamorna B; Mc Gee, Margaret M; Somma, Maria Patrizia; Nasi, Sergio; Seoane, Joan; Evan, Gerard I; Soucek, Laura

2014-08-18

Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells.

Ending on a positive: Examining the role of safety leadership decisions, behaviours and actions in a safety critical situation.

Science.gov (United States)

Donovan, Sarah-Louise; Salmon, Paul M; Horberry, Timothy; Lenné, Michael G

2018-01-01

Safety leadership is an important factor in supporting safe performance in the workplace. The present case study examined the role of safety leadership during the Bingham Canyon Mine high-wall failure, a significant mining incident in which no fatalities or injuries were incurred. The Critical Decision Method (CDM) was used in conjunction with a self-reporting approach to examine safety leadership in terms of decisions, behaviours and actions that contributed to the incidents' safe outcome. Mapping the analysis onto Rasmussen's Risk Management Framework (Rasmussen, 1997), the findings demonstrate clear links between safety leadership decisions, and emergent behaviours and actions across the work system. Communication and engagement based decisions featured most prominently, and were linked to different leadership practices across the work system. Further, a core sub-set of CDM decision elements were linked to the open flow and exchange of information across the work system, which was critical to supporting the safe outcome. The findings provide practical implications for the development of safety leadership capability to support safety within the mining industry. Copyright © 2017 Elsevier Ltd. All rights reserved.

C-terminus glycans with critical functional role in the maturation of secretory glycoproteins.

Directory of Open Access Journals (Sweden)

Daniela Cioaca

Full Text Available The N-glycans of membrane glycoproteins are mainly exposed to the extracellular space. Human tyrosinase is a transmembrane glycoprotein with six or seven bulky N-glycans exposed towards the lumen of subcellular organelles. The central active site region of human tyrosinase is modeled here within less than 2.5 Å accuracy starting from Streptomyces castaneoglobisporus tyrosinase. The model accounts for the last five C-terminus glycosylation sites of which four are occupied and indicates that these cluster in two pairs--one in close vicinity to the active site and the other on the opposite side. We have analyzed and compared the roles of all tyrosinase N-glycans during tyrosinase processing with a special focus on the proximal to the active site N-glycans, s6:N337 and s7:N371, versus s3:N161 and s4:N230 which decorate the opposite side of the domain. To this end, we have constructed mutants of human tyrosinase in which its seven N-glycosylation sites were deleted. Ablation of the s6:N337 and s7:N371 sites arrests the post-translational productive folding process resulting in terminally misfolded mutants subjected to degradation through the mannosidase driven ERAD pathway. In contrast, single mutants of the other five N-glycans located either opposite to the active site or into the N-terminus Cys1 extension of tyrosinase are temperature-sensitive mutants and recover enzymatic activity at the permissive temperature of 31°C. Sites s3 and s4 display selective calreticulin binding properties. The C-terminus sites s7 and s6 are critical for the endoplasmic reticulum retention and intracellular disposal. Results herein suggest that individual N-glycan location is critical for the stability, regional folding control and secretion of human tyrosinase and explains some tyrosinase gene missense mutations associated with oculocutaneous albinism type I.

The critical role of nurses to the successful implementation of the National Safety and Quality Health Service Standards.

Science.gov (United States)

Twigg, Diane E; Duffield, Christine; Evans, Gemma

2013-09-01

The National Safety and Quality Health Service Standards requires health service compliance by 2013 and covers several areas including governance arrangements, partnerships with consumers and eight key clinical processes. Nurses in Australia comprise 62% of the hospital workforce, are the largest component and hence play a critical role in meeting these standards and improving the quality of patient care. Several of the standards are influenced by nursing interventions, which incorporate any direct-care treatment that the nurse performs for a patient that may be nurse or physician initiated. The ability for nurses to undertake these interventions is influenced by the hours of care available, the skill mix of the nursing workforce and the environment in which they practice. Taking into consideration the predicted nursing shortages, the challenge to successfully implement the National Safety and Quality Health Service Standards will be great. This paper examines the role of nursing in the delivery of the National Standards, analyses the evidence with regard to nursing-sensitive outcomes and discusses the implications for health service decision makers and policy.

Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation

DEFF Research Database (Denmark)

Connolly, Brian M; Choi, Eun Young; Gårdsvoll, Henrik

2010-01-01

the interaction between endogenous uPA and uPAR is selectively abrogated, whereas other functions of both the protease and its receptor are retained. Specifically, we introduced 4 amino acid substitutions into the growth factor domain (GFD) of uPA that abrogate uPAR binding while preserving the overall structure...... a principal in vivo role of the uPA-uPAR interaction in cell-associated fibrinolysis critical for suppression of fibrin accumulation and fibrin-associated inflammation and provides a valuable model for further exploration of this multifunctional receptor....

Critical nodes in signalling pathways

DEFF Research Database (Denmark)

Taniguchi, Cullen M; Emanuelli, Brice; Kahn, C Ronald

2006-01-01

Physiologically important cell-signalling networks are complex, and contain several points of regulation, signal divergence and crosstalk with other signalling cascades. Here, we use the concept of 'critical nodes' to define the important junctions in these pathways and illustrate their unique role...... using insulin signalling as a model system....

Evidence and its uses in health care and research: the role of critical thinking.

Science.gov (United States)

Jenicek, Milos; Croskerry, Pat; Hitchcock, David L

2011-01-01

Obtaining and critically appraising evidence is clearly not enough to make better decisions in clinical care. The evidence should be linked to the clinician's expertise, the patient's individual circumstances (including values and preferences), and clinical context and settings. We propose critical thinking and decision-making as the tools for making that link. Critical thinking is also called for in medical research and medical writing, especially where pre-canned methodologies are not enough. It is also involved in our exchanges of ideas at floor rounds, grand rounds and case discussions; our communications with patients and lay stakeholders in health care; and our writing of research papers, grant applications and grant reviews. Critical thinking is a learned process which benefits from teaching and guided practice like any discipline in health sciences. Training in critical thinking should be a part or a pre-requisite of the medical curriculum.

Evidence and its uses in health care and research: The role of critical thinking

Science.gov (United States)

Jenicek, Milos; Croskerry, Pat; Hitchcock, David L.

2011-01-01

Summary Obtaining and critically appraising evidence is clearly not enough to make better decisions in clinical care. The evidence should be linked to the clinician’s expertise, the patient’s individual circumstances (including values and preferences), and clinical context and settings. We propose critical thinking and decision-making as the tools for making that link. Critical thinking is also called for in medical research and medical writing, especially where pre-canned methodologies are not enough. It is also involved in our exchanges of ideas at floor rounds, grand rounds and case discussions; our communications with patients and lay stakeholders in health care; and our writing of research papers, grant applications and grant reviews. Critical thinking is a learned process which benefits from teaching and guided practice like any discipline in health sciences. Training in critical thinking should be a part or a pre-requisite of the medical curriculum. PMID:21169920

Genetic Diversity and Population Structure of the Critically Endangered Yangtze Finless Porpoise (Neophocaena asiaeorientalis asiaeorientalis as Revealed by Mitochondrial and Microsatellite DNA

Directory of Open Access Journals (Sweden)

Minmin Chen

2014-06-01

Full Text Available Ecological surveys have indicated that the population of the critically endangered Yangtze finless porpoise (YFP, Neophocaena asiaeorientalis asiaeorientalis is becoming increasingly small and fragmented, and will be at high risk of extinction in the near future. Genetic conservation of this population will be an important component of the long-term conservation effort. We used a 597 base pair mitochondrial DNA (mtDNA control region and 11 microsatellite loci to analyze the genetic diversity and population structure of the YFP. The analysis of both mtDNA and microsatellite loci suggested that the genetic diversity of the YFP will possibly decrease in the future if the population keeps declining at a rapid rate, even though these two types of markers revealed different levels of genetic diversity. In addition, mtDNA revealed strong genetic differentiation between one local population, Xingchang–Shishou (XCSS, and the other five downstream local populations; furthermore, microsatellite DNA unveiled fine but significant genetic differentiation between three of the local populations (not only XCSS but also Poyang Lake (PY and Tongling (TL and the other local populations. With an increasing number of distribution gaps appearing in the Yangtze main steam, the genetic differentiation of local populations will likely intensify in the future. The YFP is becoming a genetically fragmented population. Therefore, we recommend attention should be paid to the genetic conservation of the YFP.

Genetic Diversity and Population Structure of the Critically Endangered Yangtze Finless Porpoise (Neophocaena asiaeorientalis asiaeorientalis) as Revealed by Mitochondrial and Microsatellite DNA

Science.gov (United States)

Chen, Minmin; Zheng, Jinsong; Wu, Min; Ruan, Rui; Zhao, Qingzhong; Wang, Ding

2014-01-01

Ecological surveys have indicated that the population of the critically endangered Yangtze finless porpoise (YFP, Neophocaena asiaeorientalis asiaeorientalis) is becoming increasingly small and fragmented, and will be at high risk of extinction in the near future. Genetic conservation of this population will be an important component of the long-term conservation effort. We used a 597 base pair mitochondrial DNA (mtDNA) control region and 11 microsatellite loci to analyze the genetic diversity and population structure of the YFP. The analysis of both mtDNA and microsatellite loci suggested that the genetic diversity of the YFP will possibly decrease in the future if the population keeps declining at a rapid rate, even though these two types of markers revealed different levels of genetic diversity. In addition, mtDNA revealed strong genetic differentiation between one local population, Xingchang–Shishou (XCSS), and the other five downstream local populations; furthermore, microsatellite DNA unveiled fine but significant genetic differentiation between three of the local populations (not only XCSS but also Poyang Lake (PY) and Tongling (TL)) and the other local populations. With an increasing number of distribution gaps appearing in the Yangtze main steam, the genetic differentiation of local populations will likely intensify in the future. The YFP is becoming a genetically fragmented population. Therefore, we recommend attention should be paid to the genetic conservation of the YFP. PMID:24968271

Critical superheats upon boiling of dissociating liquids

International Nuclear Information System (INIS)

Kolykhan, L.I.; Solov'ev, V.N.

1985-01-01

The experimental data on critical superheats of dissociating liquids, i.e. nitrogen tetroxide and nitrine are presented (nitrine is the solution of nitrogen oxide in nitrogen tetroxide). The experiments with boiling N 2 O 4 have been carried out in the pressure range 0.1-3.0 MPa and with boiling nitrine within the pressure range 0.2-9.0 MPa. The experiments have revealed an anomalous dependence of critical superheats on pressure P, thus at P>=2.5 MPa the critical superheat values exceed the limiting ones, and at P=4.5 MPa this excess amounts to more than 16 K, essentially exceeding the errors of the experiments. The results for N 2 O 4 critical superheats agree with experimental data of other authors. Complex phenomena observed upon boiling of dissociating liquids require further theoretical and experimental studies

Structural and functional studies of the biotin protein ligase from Aquifex aeolicus reveal a critical role for a conserved residue in target specificity.

Science.gov (United States)

Tron, Cecile M; McNae, Iain W; Nutley, Margaret; Clarke, David J; Cooper, Alan; Walkinshaw, Malcolm D; Baxter, Robert L; Campopiano, Dominic J

2009-03-20

Biotin protein ligase (BPL; EC 6.3.4.15) catalyses the formation of biotinyl-5'-AMP from biotin and ATP, and the succeeding biotinylation of the biotin carboxyl carrier protein. We describe the crystal structures, at 2.4 A resolution, of the class I BPL from the hyperthermophilic bacteria Aquifex aeolicus (AaBPL) in its ligand-free form and in complex with biotin and ATP. The solvent-exposed beta- and gamma-phosphates of ATP are located in the inter-subunit cavity formed by the N- and C-terminal domains. The Arg40 residue from the conserved GXGRXG motif is shown to interact with the carboxyl group of biotin and to stabilise the alpha- and beta-phosphates of the nucleotide. The structure of the mutant AaBPL R40G in both the ligand-free and biotin-bound forms reveals that the mutated loop has collapsed, thus hindering ATP binding. Isothermal titration calorimetry indicated that the presence of biotin is not required for ATP binding to wild-type AaBPL in the absence of Mg(2+), and the binding of biotin and ATP has been determined to occur via a random but cooperative process. The affinity for biotin is relatively unaffected by the R40G mutation. In contrast, the thermodynamic data indicate that binding of ATP to AaBPL R40G is very weak in the absence or in the presence of biotin. The AaBPL R40G mutant remains catalytically active but shows poor substrate specificity; mass spectrometry and Western blot studies revealed that the mutant biotinylates both the target A. aeolicus BCCPDelta67 fragment and BSA, and is subject to self-biotinylation.

Truly Funny: Humor, Irony, and Satire as Moral Criticism

Science.gov (United States)

Dadlez, E. M.

2011-01-01

The occasional role of humor as a vehicle for moral criticism is investigated. I begin by distinguishing between this particular role and the other kinds of ways in which humor and amusement might be regarded through a moral lens, consider historical approaches to humor that corroborate the kind of role for it on which my investigation focuses,…

Separable roles of UFO during floral development revealed by conditional restoration of gene function.

Science.gov (United States)

Laufs, Patrick; Coen, Enrico; Kronenberger, Jocelyne; Traas, Jan; Doonan, John

2003-02-01

The UNUSUAL FLORAL ORGANS (UFO) gene is required for several aspects of floral development in Arabidopsis including specification of organ identity in the second and third whorls and the proper pattern of primordium initiation in the inner three whorls. UFO is expressed in a dynamic pattern during the early phases of flower development. Here we dissect the role of UFO by ubiquitously expressing it in ufo loss-of-function flowers at different developmental stages and for various durations using an ethanol-inducible expression system. The previously known functions of UFO could be separated and related to its expression at specific stages of development. We show that a 24- to 48-hour period of UFO expression from floral stage 2, before any floral organs are visible, is sufficient to restore normal petal and stamen development. The earliest requirement for UFO is during stage 2, when the endogenous UFO gene is transiently expressed in the centre of the wild-type flower and is required to specify the initiation patterns of petal, stamen and carpel primordia. Petal and stamen identity is determined during stages 2 or 3, when UFO is normally expressed in the presumptive second and third whorl. Although endogenous UFO expression is absent from the stamen whorl from stage 4 onwards, stamen identity can be restored by UFO activation up to stage 6. We also observed floral phenotypes not observed in loss-of-function or constitutive gain-of-function backgrounds, revealing additional roles of UFO in outgrowth of petal primordia.

The Critical Role of Organic Chemistry in Drug Discovery.

Science.gov (United States)

Rotella, David P

2016-10-19

Small molecules remain the backbone for modern drug discovery. They are conceived and synthesized by medicinal chemists, many of whom were originally trained as organic chemists. Support from government and industry to provide training and personnel for continued development of this critical skill set has been declining for many years. This Viewpoint highlights the value of organic chemistry and organic medicinal chemists in the complex journey of drug discovery as a reminder that basic science support must be restored.

Intermittency-induced criticality in a resistor-inductor-diode circuit.

Science.gov (United States)

Potirakis, Stelios M; Contoyiannis, Yiannis; Diakonos, Fotios K; Hanias, Michael P

2017-04-01

The current fluctuations of a driven resistor-inductor-diode circuit are investigated here looking for signatures of critical behavior monitored by the driving frequency. The experimentally obtained time series of the voltage drop across the resistor (as directly proportional to the current flowing through the circuit) were analyzed by means of the method of critical fluctuations in analogy to thermal critical systems. Intermittent criticality was revealed for a critical frequency band signifying the transition between the normal rectifier phase in the low frequencies and a full-wave conducting, capacitorlike phase in the high frequencies. The transition possesses critical characteristics with a characteristic exponent p_{l}=1.65. A fractal analysis in terms of the rescale range (R/RSS) and detrended fluctuation analysis methods yielded results fully compatible with the critical dynamics analysis. Suggestions for the interpretation of the observed behavior in terms of p-n junction operation are discussed.

Racial Inequality in Critical Thinking Skills: The Role of Academic and Diversity Experiences

Science.gov (United States)

Roksa, Josipa; Trolian, Teniell L.; Pascarella, Ernest T.; Kilgo, Cindy A.; Blaich, Charles; Wise, Kathleen S.

2017-01-01

While racial inequalities in college entry and completion are well documented, much less is known about racial disparities in the development of general collegiate skills, such as critical thinking. Using data from the Wabash National Study of Liberal Arts Education, we find substantial inequality in the development of critical thinking skills…

Critical perspectives in public health

National Research Council Canada - National Science Library

Green, Judith; Labonte, Ronald N

2008-01-01

... the contemporary roles of 'critical voices' in public health research and practice from a range of disciplines and contexts. The book covers many of the pressing concerns for public health practitioners and researchers, including: * * * * * the implications of new genetic technologies for public health; the impact of globalisation on local practice...

The critical role of extreme heat for maize production in the United States

Science.gov (United States)

Lobell, David B.; Hammer, Graeme L.; McLean, Greg; Messina, Carlos; Roberts, Michael J.; Schlenker, Wolfram

2013-05-01

Statistical studies of rainfed maize yields in the United States and elsewhere have indicated two clear features: a strong negative yield response to accumulation of temperatures above 30°C (or extreme degree days (EDD)), and a relatively weak response to seasonal rainfall. Here we show that the process-based Agricultural Production Systems Simulator (APSIM) is able to reproduce both of these relationships in the Midwestern United States and provide insight into underlying mechanisms. The predominant effects of EDD in APSIM are associated with increased vapour pressure deficit, which contributes to water stress in two ways: by increasing demand for soil water to sustain a given rate of carbon assimilation, and by reducing future supply of soil water by raising transpiration rates. APSIM computes daily water stress as the ratio of water supply to demand, and during the critical month of July this ratio is three times more responsive to 2°C warming than to a 20% precipitation reduction. The results suggest a relatively minor role for direct heat stress on reproductive organs at present temperatures in this region. Effects of elevated CO2 on transpiration efficiency should reduce yield sensitivity to EDD in the coming decades, but at most by 25%.

Nuclear criticality safety in Canada

International Nuclear Information System (INIS)

Shultz, K.R.

1980-04-01

The approach taken to nuclear criticality safety in Canada has been influenced by the historical development of participants. The roles played by governmental agencies and private industry since the Atomic Energy Control Act was passed into Canadian Law in 1946 are outlined to set the scene for the current situation and directions that may be taken in the future. Nuclear criticality safety puts emphasis on the control of materials called special fissionable material in Canada. A brief account is given of the historical development and philosophy underlying the existing regulations governing special fissionable material. Subsequent events have led to a change in emphasis in the regulatory process that has not yet been fully integrated into Canadian legislation and regulations. Current efforts towards further development of regulations governing the practice of nuclear criticality safety are described. (auth)

Criticality assessment of LLRWDF closure

International Nuclear Information System (INIS)

Sarrack, A.G.; Weber, J.H.; Woody, N.D.

1992-01-01

During the operation of the Low Level Radioactive Waste Disposal Facility (LLRWDF), large amounts (greater than 100 kg) of enriched uranium (EU) were buried. This EU came primarily from the closing and decontamination of the Naval Fuels Facility in the time period from 1987--1989. Waste Management Operations (WMO) procedures were used to keep the EU boxes separated to prevent possible criticality during normal operation. Closure of the LLRWDF is currently being planned, and waste stabilization by Dynamic Compaction (DC) is proposed. Dynamic compaction will crush the containers in the LLRWDF and result in changes in their geometry. Research of the LLRWDF operations and record keeping practices have shown that the EU contents of trenches are known, but details of the arrangement of the contents cannot be proven. Reviews of the trench contents, combined with analysis of potential critical configurations, revealed that some portions of the LLRWDF can be expected to be free of criticality concerns while other sections have credible probabilities for the assembly of a critical mass, even in the uncompacted configuration. This will have an impact on the closure options and which trenches can be compacted

The Department of Energy nuclear criticality safety program

International Nuclear Information System (INIS)

Felty, J.R.

2004-01-01

This paper broadly covers key events and activities from which the Department of Energy Nuclear Criticality Safety Program (NCSP) evolved. The NCSP maintains fundamental infrastructure that supports operational criticality safety programs. This infrastructure includes continued development and maintenance of key calculational tools, differential and integral data measurements, benchmark compilation, development of training resources, hands-on training, and web-based systems to enhance information preservation and dissemination. The NCSP was initiated in response to Defense Nuclear Facilities Safety Board Recommendation 97-2, Criticality Safety, and evolved from a predecessor program, the Nuclear Criticality Predictability Program, that was initiated in response to Defense Nuclear Facilities Safety Board Recommendation 93-2, The Need for Critical Experiment Capability. This paper also discusses the role Dr. Sol Pearlstein played in helping the Department of Energy lay the foundation for a robust and enduring criticality safety infrastructure.

Critical bioethics in the time of epidemic: The case of the criminalization of HIV/AIDS nondisclosure in Canada

Directory of Open Access Journals (Sweden)

Jennifer M. Kilty

2017-01-01

Full Text Available This article highlights the ethically uncertain and emotionally charged climate that governs the criminalization of HIV nondisclosure in Canada. Focusing on AIDS Service Organizations (ASO, we suggest that interlocutors perform critical work that helps people living with HIV/AIDS make sense of their rights and responsibilities. Semi-structured interviews with 62 ASO staff across Canada revealed this shifting landscape of HIV advocacy in the age of criminalizing HIV nondisclosure. Drawing on a critical bioethics approach that is informed by considering the role of emotion in decision-making, this article critiques the liberal model of the rational actor that is central to traditional discussions of bioethics and law. Our findings suggest that ASO workers have varying degrees of knowledge about the intricacies of legal duties of disclosure, which affect how they balance their own emotions and thoughts about nondisclosure with their professional duties to provide support and counselling. Ultimately, we argue that critical bioethics in the context of criminalization commands us to appreciate the inherently affective nature of the environment in which bioethical decisions are made.

Nanoimprinted backside reflectors for a-Si:H thin-film solar cells: critical role of absorber front textures.

Science.gov (United States)

Tsao, Yao-Chung; Fisker, Christian; Pedersen, Thomas Garm

2014-05-05

The development of optimal backside reflectors (BSRs) is crucial for future low cost and high efficiency silicon (Si) thin-film solar cells. In this work, nanostructured polymer substrates with aluminum coatings intended as BSRs were produced by positive and negative nanoimprint lithography (NIL) techniques, and hydrogenated amorphous silicon (a-Si:H) was deposited hereon as absorbing layers. The relationship between optical properties and geometry of front textures was studied by combining experimental reflectance spectra and theoretical simulations. It was found that a significant height variation on front textures plays a critical role for light-trapping enhancement in solar cell applications. As a part of sample preparation, a transfer NIL process was developed to overcome the problem of low heat deflection temperature of polymer substrates during solar cell fabrication.

Updating appetitive memory during reconsolidation window: critical role of cue-directed behavior and amygdala central nucleus.

Science.gov (United States)

Olshavsky, Megan E; Song, Bryan J; Powell, Daniel J; Jones, Carolyn E; Monfils, Marie-H; Lee, Hongjoo J

2013-01-01

When presented with a light cue followed by food, some rats simply approach the foodcup (Nonorienters), while others first orient to the light in addition to displaying the food-cup approach behavior (Orienters). Cue-directed orienting may reflect enhanced attentional and/or emotional processing of the cue, suggesting divergent natures of cue-information processing in Orienters and Nonorienters. The current studies investigate how differences in cue processing might manifest in appetitive memory retrieval and updating using a paradigm developed to persistently attenuate fear responses (Retrieval-extinction paradigm; Monfils et al., 2009). First, we examined whether the retrieval-extinction paradigm could attenuate appetitive responses in Orienters and Nonorienters. Next, we investigated if the appetitive memory could be updated using reversal learning (fear conditioning) during the reconsolidation window (as opposed to repeated unreinforced trials, i.e., extinction). Both extinction and new fear learning given within the reconsolidation window were effective at persistently updating the initial appetitive memory in the Orienters, but not the Nonorienters. Since conditioned orienting is mediated by the amygdala central nucleus (CeA), our final experiment examined the CeA's role in the retrieval-extinction process. Bilateral CeA lesions interfered with the retrieval-extinction paradigm-did not prevent spontaneous recovery of food-cup approach. Together, our studies demonstrate the critical role of conditioned orienting behavior and the CeA in updating appetitive memory during the reconsolidation window.

The Limited Role of Journalism Professors in Direct Media Criticism.

Science.gov (United States)

Bass, Abraham Z.

This paper discusses reasons why few journalism professors are personally confronting the news media with criticism or praise. One of the primary reasons for this is that journalism professors may fear retribution or keep inbred ties with the media or be following academic tradition. A survey was conducted in Spring 1975 for this report. The…

Critical incident analysis through narrative reflective practice: A case study

Directory of Open Access Journals (Sweden)

Thomas S. C. Farrell

2013-01-01

Full Text Available Teachers can reflect on their practices by articulating and exploring incidents they consider critical to themselves or others. By talking about these critical incidents, teachers can make better sense of seemingly random experiences that occur in their teaching because they hold the real inside knowledge, especially personal intuitive knowledge, expertise and experience that is based on their accumulated years as language educators teaching in schools and classrooms. This paper is about one such critical incident analysis that an ESL teacher in Canada revealed to her critical friend and how both used McCabe’s (2002 narrative framework for analyzing an important critical incident that occurred in the teacher’s class.

Criticality safety analysis for mockup facility

International Nuclear Information System (INIS)

Shin, Young Joon; Shin, Hee Sung; Kim, Ik Soo; Oh, Seung Chul; Ro, Seung Gy; Bae, Kang Mok

2000-03-01

Benchmark calculations for SCALE4.4 CSAS6 module have been performed for 31 UO 2 fuel, 15MOX fuel and 10 metal material criticality experiments and then calculation biases of the SCALE 4.4 CSAS6 module have been revealed to be 0.00982, 0.00579 and 0.02347, respectively. When CSAS6 is applied to the criticality safety analysis for the mockup facility in which several kinds of nuclear material components are included, the calculation bias of CSAS6 is conservatively taken to be 0.02347. With the aid of this benchmarked code system, criticality safety analyses for the mockup facility at normal and hypothetical accidental conditions have been carried out. It appears that the maximum K eff is 0.28356 well below than the critical limit, K eff =0.95 at normal condition. In a hypothetical accidental condition, the maximum K eff is found to be 0.73527 much lower than the subcritical limit. For another hypothetical accidental condition the nuclear material leaks out of container and spread or lump in the floor, it was assumed that the nuclear material is shaped into a slab and water exists in the empty space of the nuclear material. K eff has been calculated as function of slab thickness and the volume ratio of water to nuclear material. The result shows that the K eff increases as the water volume ratio increases. It is also revealed that the K eff reaches to the maximum value when water if filled in the empty space of nuclear material. The maximum K eff value is 0.93960 lower than the subcritical limit

Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells.

Science.gov (United States)

Rusin, Scott F; Schlosser, Kate A; Adamo, Mark E; Kettenbach, Arminja N

2015-10-13

Protein phosphorylation is an important regulatory mechanism controlling mitotic progression. Protein phosphatase 6 (PP6) is an essential enzyme with conserved roles in chromosome segregation and spindle assembly from yeast to humans. We applied a baculovirus-mediated gene silencing approach to deplete HeLa cells of the catalytic subunit of PP6 (PP6c) and analyzed changes in the phosphoproteome and proteome in mitotic cells by quantitative mass spectrometry-based proteomics. We identified 408 phosphopeptides on 272 proteins that increased and 298 phosphopeptides on 220 proteins that decreased in phosphorylation upon PP6c depletion in mitotic cells. Motif analysis of the phosphorylated sites combined with bioinformatics pathway analysis revealed previously unknown PP6c-dependent regulatory pathways. Biochemical assays demonstrated that PP6c opposed casein kinase 2-dependent phosphorylation of the condensin I subunit NCAP-G, and cellular analysis showed that depletion of PP6c resulted in defects in chromosome condensation and segregation in anaphase, consistent with dysregulation of condensin I function in the absence of PP6 activity. Copyright © 2015, American Association for the Advancement of Science.

Body Image, Self-Esteem, and Weight-Related Criticism from Romantic Partners.

Science.gov (United States)

Befort, Christie; Kurpius, Sharon E. Robinson; Hull-Blanks, Elva; Nicpon, Megan Foley; Huser, Laura; Sollenberger, Sonja

2001-01-01

Examines weight-related criticism from romantic partners and the importance of the romantic relationship in relation to the body image and self esteem for college freshmen women. Results reveal that self esteem and body image were positively related. Partner importance also predicted self esteem, whereas criticism did not. (Contains 55 references…

Enhancement of Students' Independent Learning through Their Critical Thinking Skills Development

Science.gov (United States)

Kopzhassarova, Umit; Akbayeva, Gulden; Eskazinova, Zhanar; Belgibayeva, Gulbarshyn; Tazhikeyeva, Akerke

2016-01-01

The article focuses on the problem of developing students' critical thinking skills, which help them become independent learners. Analysis of research works of educators and scholars enable the authors to reveal qualities, necessary for students to enhance their critical thinking skills and become independent learners. Different points of view on…

Toward an improved understanding of the role of transpiration in critical zone dynamics

Science.gov (United States)

Mitra, B.; Papuga, S. A.

2012-12-01

, during the snowmelt period, Ts across multiple depths was the primary control on the sap flux rate (R2 ≈ 0.7). During the dry and monsoon periods only net radiation (Rn) was found to be a driver of the flux rate (R2 ≈ 0.4). For JRB spruce, a combination of Ts across multiple depths as well as air temperature (R2 ≈ 0.5) were the dominant drivers of sap flux rate during the snowmelt period. During the monsoon period, Rn (R2 ≈ 0.4) was the dominant driver. For SCM maple, during the dry period, θ across multiple depths was the primary driver of the sap flux rate (R2 ≈ 0.8); the strength of the correlation with the control of θ on sap flux rate drastically dropping (R2 ≈ 0.2) during the monsoon period. For SCM white fir, θ across multiple depths was a weak driver of sap flux rate during the dry (R2 ≈ 0.1) and monsoon periods (R2 ≈ 0.2). This study highlights the importance of species-specific information for understanding the role of transpiration in critical zone processes. Specifically, unique environmental drivers that vary throughout the year for different vegetation types complicate the assessment of both catchment-scale water and carbon balances and for understanding of the processes that govern the complex dynamics across the CZ.

Natural time analysis of critical phenomena: The case of pre-fracture electromagnetic emissions

Energy Technology Data Exchange (ETDEWEB)

Potirakis, S. M. [Department of Electronics, Technological Education Institute (TEI) of Piraeus, 250 Thivon and P. Ralli, Aigaleo, Athens GR-12244 (Greece); Karadimitrakis, A. [Department of Physics, Section of Electronics, Computers, Telecommunications and Control, University of Athens, Panepistimiopolis, Zografos, Athens GR-15784 (Greece); Eftaxias, K. [Department of Physics, Section of Solid State Physics, University of Athens, Panepistimiopolis, Zografos, Athens GR-15784 (Greece)

2013-06-15

Criticality of complex systems reveals itself in various ways. One way to monitor a system at critical state is to analyze its observable manifestations using the recently introduced method of natural time. Pre-fracture electromagnetic (EM) emissions, in agreement to laboratory experiments, have been consistently detected in the MHz band prior to significant earthquakes. It has been proposed that these emissions stem from the fracture of the heterogeneous materials surrounding the strong entities (asperities) distributed along the fault, preventing the relative slipping. It has also been proposed that the fracture of heterogeneous material could be described in analogy to the critical phase transitions in statistical physics. In this work, the natural time analysis is for the first time applied to the pre-fracture MHz EM signals revealing their critical nature. Seismicity and pre-fracture EM emissions should be two sides of the same coin concerning the earthquake generation process. Therefore, we also examine the corresponding foreshock seismic activity, as another manifestation of the same complex system at critical state. We conclude that the foreshock seismicity data present criticality features as well.

Natural time analysis of critical phenomena: the case of pre-fracture electromagnetic emissions.

Science.gov (United States)

Potirakis, S M; Karadimitrakis, A; Eftaxias, K

2013-06-01

Criticality of complex systems reveals itself in various ways. One way to monitor a system at critical state is to analyze its observable manifestations using the recently introduced method of natural time. Pre-fracture electromagnetic (EM) emissions, in agreement to laboratory experiments, have been consistently detected in the MHz band prior to significant earthquakes. It has been proposed that these emissions stem from the fracture of the heterogeneous materials surrounding the strong entities (asperities) distributed along the fault, preventing the relative slipping. It has also been proposed that the fracture of heterogeneous material could be described in analogy to the critical phase transitions in statistical physics. In this work, the natural time analysis is for the first time applied to the pre-fracture MHz EM signals revealing their critical nature. Seismicity and pre-fracture EM emissions should be two sides of the same coin concerning the earthquake generation process. Therefore, we also examine the corresponding foreshock seismic activity, as another manifestation of the same complex system at critical state. We conclude that the foreshock seismicity data present criticality features as well.

Natural time analysis of critical phenomena: The case of pre-fracture electromagnetic emissions

International Nuclear Information System (INIS)

Potirakis, S. M.; Karadimitrakis, A.; Eftaxias, K.

2013-01-01

Criticality of complex systems reveals itself in various ways. One way to monitor a system at critical state is to analyze its observable manifestations using the recently introduced method of natural time. Pre-fracture electromagnetic (EM) emissions, in agreement to laboratory experiments, have been consistently detected in the MHz band prior to significant earthquakes. It has been proposed that these emissions stem from the fracture of the heterogeneous materials surrounding the strong entities (asperities) distributed along the fault, preventing the relative slipping. It has also been proposed that the fracture of heterogeneous material could be described in analogy to the critical phase transitions in statistical physics. In this work, the natural time analysis is for the first time applied to the pre-fracture MHz EM signals revealing their critical nature. Seismicity and pre-fracture EM emissions should be two sides of the same coin concerning the earthquake generation process. Therefore, we also examine the corresponding foreshock seismic activity, as another manifestation of the same complex system at critical state. We conclude that the foreshock seismicity data present criticality features as well.

[Role of creative discussion in the learning of critical reading of scientific articles].

Science.gov (United States)

Cobos-Aguilar, Héctor; Viniegra-Velázquez, Leonardo; Pérez-Cortés, Patricia

2011-01-01

To compare two active educational strategies on critical reading (two and three stages) for research learning in medical students. Four groups were conformed in a quasi-experimental design. The medical student group, related to three stages (critical reading guide resolution, creative discussion, group discussion) g1, n = 9 with school marks > 90 and g2, n = 19 with a learning in our students.

Crystal structure of Clostridium botulinum whole hemagglutinin reveals a huge triskelion-shaped molecular complex.

Science.gov (United States)

Amatsu, Sho; Sugawara, Yo; Matsumura, Takuhiro; Kitadokoro, Kengo; Fujinaga, Yukako

2013-12-06

Clostridium botulinum HA is a component of the large botulinum neurotoxin complex and is critical for its oral toxicity. HA plays multiple roles in toxin penetration in the gastrointestinal tract, including protection from the digestive environment, binding to the intestinal mucosal surface, and disruption of the epithelial barrier. At least two properties of HA contribute to these roles: the sugar-binding activity and the barrier-disrupting activity that depends on E-cadherin binding of HA. HA consists of three different proteins, HA1, HA2, and HA3, whose structures have been partially solved and are made up mainly of β-strands. Here, we demonstrate structural and functional reconstitution of whole HA and present the complete structure of HA of serotype B determined by x-ray crystallography at 3.5 Å resolution. This structure reveals whole HA to be a huge triskelion-shaped molecule. Our results suggest that whole HA is functionally and structurally separable into two parts: HA1, involved in recognition of cell-surface carbohydrates, and HA2-HA3, involved in paracellular barrier disruption by E-cadherin binding.

CriticalEd

DEFF Research Database (Denmark)

Kjellberg, Caspar Mølholt; Meredith, David

2014-01-01

. Since the comments are not input sequentially, with regard to position, but in arbitrary order, this list must be sorted by copy/pasting the rows into place—an error-prone and time-consuming process. Scholars who produce critical editions typically use off-the-shelf music notation software......The best text method is commonly applied among music scholars engaged in producing critical editions. In this method, a comment list is compiled, consisting of variant readings and editorial emendations. This list is maintained by inserting the comments into a document as the changes are made......, consisting of a Sibelius plug-in, a cross-platform application, called CriticalEd, and a REST-based solution, which handles data storage/retrieval. A prototype has been tested at the Danish Centre for Music Publication, and the results suggest that the system could greatly improve the efficiency...

History of pulmonary critical care nursing and where we are going.

Science.gov (United States)

Lareau, Suzanne C; Mealer, Meredith

2012-09-01

Pulmonary critical care nurses have played a prominent role in the ICUs from the inception of critical care units. This article describes how the history of pulmonary critical care nursing has evolved and discusses a few of the challenges in the years to come: stress imposed by working in a critical care environment, enhancing the care of patients by altering patterns of sedation and promoting early mobilization, and dealing with increasing infection rates.

Role of controllability in optimizing quantum dynamics

International Nuclear Information System (INIS)

Wu Rebing; Hsieh, Michael A.; Rabitz, Herschel

2011-01-01

This paper reveals an important role that controllability plays in the complexity of optimizing quantum control dynamics. We show that the loss of controllability generally leads to multiple locally suboptimal controls when gate fidelity in a quantum control system is maximized, which does not happen if the system is controllable. Such local suboptimal controls may attract an optimization algorithm into a local trap when a global optimal solution is sought, even if the target gate can be perfectly realized. This conclusion results from an analysis of the critical topology of the corresponding quantum control landscape, which refers to the gate fidelity objective as a functional of the control fields. For uncontrollable systems, due to SU(2) and SU(3) dynamical symmetries, the control landscape corresponding to an implementable target gate is proven to possess multiple locally optimal critical points, and its ruggedness can be further increased if the target gate is not realizable. These results imply that the optimization of quantum dynamics can be seriously impeded when operating with local search algorithms under these conditions, and thus full controllability is demanded.

Pathos in Criticism: Edwin Black's Communism-as-Cancer Metaphor

Science.gov (United States)

Condit, Celeste M.

2013-01-01

Edwin Black's essay on "The Second Persona," introduced to rhetorical critics a rationale and model for a type of ideological criticism. Because it ignored the role of pathos in both the rhetoric Black purported to critique and in the construction of his own audience, Black's essay mis-described key features of Robert Welch's "Blue Book", which…

A Critical Discourse Analysis of the Images of Iranians in Western Movies: The Case of Iranium

Directory of Open Access Journals (Sweden)

Mohammad Reza Amirian

2012-09-01

Full Text Available The significant role of the media, in general, and the movies, in particular, in disseminating information and creating images of the real life by use of the language as a powerful social tool is totally irrefutable. Although critical analysis of the movie discourse is a fashionable trend among the critical discourse analysts, there is a paucity of research on movie discourse in Iran. Besides, the increasing number of the anti-Iranian movies produced in the last decade and the growing tendency among the English students to watch American movies, have established the need for conducting a research to investigate the images of Iranians represented in the Western movies. Thus, in this article an anti-Iranian movie called Iranium, allegedly labeled as documentary, has been critically analyzed using Critical Discourse Analysis (CDA. For this purpose, Van Dijk’s framework (2004 has been utilized to uncover the ideological manipulations and misrepresentations of this movie. The analysis revealed that the dichotomy of in-group favoritism vs. out-group derogation is a very effective discursive strategy at the disposal of the movie makers who have used language as a weapon to attack Iran by representing a distorted and unrealistic image of the Iranians’ history, culture and ideologies. The findings of the present study imply that adopting a critical discourse analysis perspective in the EFL classes is a necessity which needs the development of the required materials, by the curriculum developers, that raise the students’ critical awareness as well as their language skills and proficiency.

Impegno 3.0. Towards participatory criticism?

Directory of Open Access Journals (Sweden)

Pierpaolo Antonello

2016-04-01

Full Text Available This essay is a general discussion on the possible contours taken by the the notion of impegno in the contemporary Italian context, seen from the point of view of critical and academic practices, particularly in the light of contextual socio-economic, technological and disciplinary changes. While an alignment with the  paradigmatic shift occurred at the international level where a number of studies have been discussing the emancipatory role of literature, cinema, and the media from the point of view of readers and audiences is felt much needed, a paradigmatic refashioning of the critical debate and of the public sphere is currently occurring, which gives rise of new possibilities for critical engagement facilitated by the so-called Web 3.0. This new media-ecology provides fora by which the critical practice is much more horizontal and democratic in nature, while authorship and readership present a more dynamic cross-fertilisation

Expanding beyond individualism: Engaging critical perspectives on occupation.

Science.gov (United States)

Gerlach, Alison J; Teachman, Gail; Laliberte-Rudman, Debbie; Aldrich, Rebecca M; Huot, Suzanne

2018-01-01

Perspectives that individualize occupation are poorly aligned with socially responsive and transformative occupation-focused research, education, and practice. Their predominant use in occupational therapy risks the perpetuation, rather than resolution, of occupational inequities. In this paper, we problematize taken-for-granted individualistic analyses of occupation and illustrate how critical theoretical perspectives can reveal the ways in which structural factors beyond an individual's immediate control and environment shape occupational possibilities and occupational engagement. Using a critically reflexive approach, we draw on three distinct qualitative research studies to examine the potential of critical theorizing for expanding beyond a reliance on individualistic analyses and practices. Our studies highlight the importance of addressing the socio-historical and political contexts of occupation and demonstrate the contribution of critical perspectives to socially responsive occupational therapy. In expanding beyond individualistic analyses of occupation, critical perspectives advance research and practices towards addressing socio-political mediators of occupational engagement and equity.

A critical role of platelet TGF-β release in podoplanin-mediated tumour invasion and metastasis.

Science.gov (United States)

Takemoto, Ai; Okitaka, Mina; Takagi, Satoshi; Takami, Miho; Sato, Shigeo; Nishio, Makoto; Okumura, Sakae; Fujita, Naoya

2017-02-08

The tumour microenvironment is critical for various characteristics of tumour malignancies. Platelets, as part of the tumour microenvironment, are associated with metastasis formation via increasing the rate of tumour embolus formation in microvasculature. However, the mechanisms underlying the ability of tumour cells to acquire invasiveness and extravasate into target organs at the site of embolization remain unclear. In this study, we reported that platelet aggregation-inducing factor podoplanin expressed on tumour cell surfaces were found to not only promote the formation of tumour-platelet aggregates via interaction with platelets, but also induced the epithelial-mesenchymal transition (EMT) of tumour cells by enhancing transforming growth factor-β (TGF-β) release from platelets. In vitro and in vivo analyses revealed that podoplanin-mediated EMT resulted in increased invasiveness and extravasation of tumour cells. Treatment of mice with a TGF-β-neutralizing antibody statistically suppressed podoplanin-mediated distant metastasis in vivo, suggesting that podoplanin promoted haematogenous metastasis in part by releasing TGF-β from platelets that was essential for EMT of tumour cells. Therefore, our findings suggested that blocking the TGF-β signalling pathway might be a promising strategy for suppressing podoplanin-mediated haematogenous metastasis in vivo.

SOX2 plays a critical role in EGFR-mediated self-renewal of human prostate cancer stem-like cells.

Science.gov (United States)

Rybak, Adrian P; Tang, Damu

2013-12-01

SOX2 is an essential transcription factor for stem cells and plays a role in tumorigenesis, however its role in prostate cancer stem cells (PCSCs) remains unclear. We report here a significant upregulation of SOX2 at both mRNA and protein levels in DU145 PCSCs propagated as suspension spheres in vitro. The expression of SOX2 in DU145 PCSCs is positively regulated by epidermal growth factor receptor (EGFR) signaling. Activation of EGFR signaling, following the addition of epidermal growth factor (EGF) or ectopic expression of a constitutively-active EGFR mutant (EGFRvIII), increased SOX2 expression and the self-renewal of DU145 PCSCs. Conversely, a small molecule EGFR inhibitor (AG1478) blocked EGFR activation, reduced SOX2 expression and inhibited PCSC self-renewal activity, implicating SOX2 in mediating EGFR-dependent self-renewal of PCSCs. In line with this notion, ectopic SOX2 expression enhanced EGF-induced self-renewal of DU145 PCSCs, while SOX2 knockdown reduced PCSC self-renewal with EGF treatment no longer capable of enhancing their propagation. Furthermore, SOX2 knockdown reduced the capacity of DU145 PCSCs to grow under anchorage-independent conditions. Finally, DU145 PCSCs generated xenograft tumors more aggressively with elevated levels of SOX2 expression compared to xenograft tumors derived from non-PCSCs. Collectively, we provide evidence that SOX2 plays a critical role in EGFR-mediated self-renewal of DU145 PCSCs. © 2013.

Structure-guided investigation of lipopolysaccharide O-antigen chain length regulators reveals regions critical for modal length control.

Science.gov (United States)

Kalynych, Sergei; Ruan, Xiang; Valvano, Miguel A; Cygler, Miroslaw

2011-08-01

The O-antigen component of the lipopolysaccharide (LPS) represents a population of polysaccharide molecules with nonrandom (modal) chain length distribution. The number of the repeat O units in each individual O-antigen polymer depends on the Wzz chain length regulator, an inner membrane protein belonging to the polysaccharide copolymerase (PCP) family. Different Wzz proteins confer vastly different ranges of modal lengths (4 to >100 repeat units), despite having remarkably conserved structural folds. The molecular mechanism responsible for the selective preference for a certain number of O units is unknown. Guided by the three-dimensional structures of PCPs, we constructed a panel of chimeric molecules containing parts of two closely related Wzz proteins from Salmonella enterica and Shigella flexneri which confer different O-antigen chain length distributions. Analysis of the O-antigen length distribution imparted by each chimera revealed the region spanning amino acids 67 to 95 (region 67 to 95), region 200 to 255, and region 269 to 274 as primarily affecting the length distribution. We also showed that there is no synergy between these regions. In particular, region 269 to 274 also influenced chain length distribution mediated by two distantly related PCPs, WzzB and FepE. Furthermore, from the 3 regions uncovered in this study, region 269 to 274 appeared to be critical for the stability of the oligomeric form of Wzz, as determined by cross-linking experiments. Together, our data suggest that chain length determination depends on regions that likely contribute to stabilize a supramolecular complex.

75 FR 75611 - Critical Infrastructure Protection Month, 2010

Science.gov (United States)

2010-12-03

...; and the public--to identify and protect our infrastructure from hazards or attack. These critical... cyber infrastructure more resilient. Working together, we can raise awareness of the important role our...

Critical constructivism: Concept and possibillities of its application in the field of education

Directory of Open Access Journals (Sweden)

Milutinović Jovana

2015-01-01

Full Text Available The paper focuses on critical constructivism which, as a perspective of social constructivism, concentrates on the role of social and cultural environment in the creation of knowledge, including critical dimensions of the transformation of social meanings and practices. The aim of the research was to critically analyse educational potentialities of critical constructivism, especially when it comes to education for active citizenship and democracy. The basic concepts of this theoretic perspective are analysed as well as their implications for education, understanding the role of the teachers, and the curricula for their initial and in-service teacher training. The research results of the effects of the teaching practice framed by the ideas of critical constructivism are also presented. It may be concluded that the critical constructivistic perspective may be of special importance for preparing pupils for the role of active citizens who will participate in further democratization of the social community, as well as for life in the uncertain world of diversity. At the same time the theoretical analysis and the research results imply that in education and teaching practice more space should be given to developing pluralistic views which can unify elements of different theoretical perspectives and acquired experiential knowledge into a coherent basis for innovative acting.

Nematic quantum critical point without magnetism in FeSe1-xSx superconductors.

Science.gov (United States)

Hosoi, Suguru; Matsuura, Kohei; Ishida, Kousuke; Wang, Hao; Mizukami, Yuta; Watashige, Tatsuya; Kasahara, Shigeru; Matsuda, Yuji; Shibauchi, Takasada

2016-07-19

In most unconventional superconductors, the importance of antiferromagnetic fluctuations is widely acknowledged. In addition, cuprate and iron-pnictide high-temperature superconductors often exhibit unidirectional (nematic) electronic correlations, including stripe and orbital orders, whose fluctuations may also play a key role for electron pairing. In these materials, however, such nematic correlations are intertwined with antiferromagnetic or charge orders, preventing the identification of the essential role of nematic fluctuations. This calls for new materials having only nematicity without competing or coexisting orders. Here we report systematic elastoresistance measurements in FeSe1-xSx superconductors, which, unlike other iron-based families, exhibit an electronic nematic order without accompanying antiferromagnetic order. We find that the nematic transition temperature decreases with sulfur content x; whereas, the nematic fluctuations are strongly enhanced. Near [Formula: see text], the nematic susceptibility diverges toward absolute zero, revealing a nematic quantum critical point. The obtained phase diagram for the nematic and superconducting states highlights FeSe1-xSx as a unique nonmagnetic system suitable for studying the impact of nematicity on superconductivity.

Endothelial marker-expressing stromal cells are critical for kidney formation.

Science.gov (United States)

Mukherjee, Elina; Maringer, Katherine; Papke, Emily; Bushnell, Daniel; Schaefer, Caitlin; Kramann, Rafael; Ho, Jacqueline; Humphreys, Benjamin D; Bates, Carlton; Sims-Lucas, Sunder

2017-09-01

Kidneys are highly vascularized and contain many distinct vascular beds. However, the origins of renal endothelial cells and roles of the developing endothelia in the formation of the kidney are unclear. We have shown that the Foxd1-positive renal stroma gives rise to endothelial marker-expressing progenitors that are incorporated within a subset of peritubular capillaries; however, the significance of these cells is unclear. The purpose of this study was to determine whether deletion of Flk1 in the Foxd1 stroma was important for renal development. To that end, we conditionally deleted Flk1 (critical for endothelial cell development) in the renal stroma by breeding-floxed Flk1 mice ( Flk1 fl/fl ) with Foxd1cre mice to generate Foxd1cre; Flk1 fl/fl ( Flk1 ST-/- ) mice. We then performed FACsorting, histological, morphometric, and metabolic analyses of Flk1 ST-/- vs. control mice. We confirmed decreased expression of endothelial markers in the renal stroma of Flk1 ST-/- kidneys via flow sorting and immunostaining, and upon interrogation of embryonic and postnatal Flk1 ST-/- mice, we found they had dilated peritubular capillaries. Three-dimensional reconstructions showed reduced ureteric branching and fewer nephrons in developing Flk1 ST-/- kidneys vs. Juvenile Flk1 ST-/- kidneys displayed renal papillary hypoplasia and a paucity of collecting ducts. Twenty-four-hour urine collections revealed that postnatal Flk1 ST-/- mice had urinary-concentrating defects. Thus, while lineage-tracing revealed that the renal cortical stroma gave rise to a small subset of endothelial progenitors, these Flk1-expressing stromal cells are critical for patterning the peritubular capillaries. Also, loss of Flk1 in the renal stroma leads to nonautonomous-patterning defects in ureteric lineages. Copyright © 2017 the American Physiological Society.

Criticality: static profiling for real-time programs

DEFF Research Database (Denmark)

Brandner, Florian; Hepp, Stefan; Jordan, Alexander

2014-01-01

With the increasing performance demand in real-time systems it becomes more and more important to provide feedback to programmers and software development tools on the performance-relevant code parts of a real-time program. So far, this information was limited to an estimation of the worst....... Experiments using well-established real-time benchmark programs show an interesting distribution of the criticality values, revealing considerable amounts of highly critical as well as uncritical code. The metric thus provides ideal information to programmers and software development tools to optimize...... view covering the entire code base, tools in the spirit of program profiling are required. This work proposes an efficient approach to compute worst-case timing information for all code parts of a program using a complementary metric, called criticality. Every statement of a program is assigned...

Technology-Critical Elements: Economic and Policy Perspectives

Science.gov (United States)

Eggert, R. G.

2017-12-01

Critical elements are those that provide essential functionality to modern engineered materials, have few ready substitutes and are subject to supply-chain risks or concerns about long-run availability. This paper provides economic and public-policy perspectives on critical elements. It suggests: that which elements are critical is situational and changes over time; that we are not running out of mineral-derived raw materials in a geologic sense but rather, for some elements, face scarcities that are technological, environmental, political or economic in nature; and that public policy's most important role over the longer term is fostering scientific and technological innovation, especially early stage research, that has the potential to overcome these scarcities.

Developing the PLA critical care medicine is critical for advancing the level of battle wound treatment in the new era

Directory of Open Access Journals (Sweden)

Wei-qin LI

2017-04-01

Full Text Available Critical care medicine is an emerging unique specialty developed from the later 20th century, since then, it has been enriched with theoretical and practical experiences and becomes the most active subject in the field of clinical medicine. Critical care medicine of the PLA has attained significant achievements in the treatment and research of severe trauma, sepsis, severe heat stroke, multiple organ failure and severe acute pancreatitis. Besides, it stands in the leading position in the organ function maintenance of critically ill patients, continuous hemofiltration and nutrition support in China. Furthermore, critical care medicine plays an important role in the rescue of critically ill patients, medical support and disaster relief. As the relationship between battle wound rescue system and critical care medicine has been increasingly close, transition in the form of war in the new period brings new tasks to battle wound treatment constantly. Combined with the characteristics of information-oriented war condition in the future, developing the PLA critical care medicine and advancing the level of battle wound treatment in the new period point out the direction for the future work of critical care medicine. DOI: 10.11855/j.issn.0577-7402.2017.02.01

Critical technologies research: Opportunities for DOE

Energy Technology Data Exchange (ETDEWEB)

1992-12-01

Recent studies have identified a number of critical technologies that are essential to the nation`s defense, economic competitiveness, energy independence, and betterment of public health. The National Critical Technologies Panel (NCTP) has identified the following critical technology areas: Aeronautics and Surface Transportation; Biotechnology and Life Sciences; Energy and Environment; Information and Communications; Manufacturing; and Materials. Sponsored by the Department of Energy`s Office of Energy Research (OER), the Critical Technologies Research Workshop was held in May 1992. Approximately 100 scientists, engineers, and managers from the national laboratories, industry, academia, and govemment participated. The objective of the Berkeley Workshop was to advance the role of the DOE multiprogram energy laboratories in critical technologies research by describing, defining, and illustrating research areas, opportunities, resources, and key decisions necessary to achieve national research goals. An agenda was developed that looked at DOE`s capabilities and options for research in critical technologies and provided a forum for industry, academia, govemment, and the national laboratories to address: Critical technology research needs; existing research activities and resources; capabilities of the national laboratories; and opportunities for national laboratories, industries, and universities. The Workshop included plenary sessions in which presentations by technology and policy leaders set the context for further inquiry into critical technology issues and research opportunities. Separate sessions then focused on each of the following major areas of technology: Advanced materials; biotechnology and life sciences; energy and environment; information and communication; and manufacturing and transportation.

Critical technologies research: Opportunities for DOE

Energy Technology Data Exchange (ETDEWEB)

1992-12-01

Recent studies have identified a number of critical technologies that are essential to the nation's defense, economic competitiveness, energy independence, and betterment of public health. The National Critical Technologies Panel (NCTP) has identified the following critical technology areas: Aeronautics and Surface Transportation; Biotechnology and Life Sciences; Energy and Environment; Information and Communications; Manufacturing; and Materials. Sponsored by the Department of Energy's Office of Energy Research (OER), the Critical Technologies Research Workshop was held in May 1992. Approximately 100 scientists, engineers, and managers from the national laboratories, industry, academia, and govemment participated. The objective of the Berkeley Workshop was to advance the role of the DOE multiprogram energy laboratories in critical technologies research by describing, defining, and illustrating research areas, opportunities, resources, and key decisions necessary to achieve national research goals. An agenda was developed that looked at DOE's capabilities and options for research in critical technologies and provided a forum for industry, academia, govemment, and the national laboratories to address: Critical technology research needs; existing research activities and resources; capabilities of the national laboratories; and opportunities for national laboratories, industries, and universities. The Workshop included plenary sessions in which presentations by technology and policy leaders set the context for further inquiry into critical technology issues and research opportunities. Separate sessions then focused on each of the following major areas of technology: Advanced materials; biotechnology and life sciences; energy and environment; information and communication; and manufacturing and transportation.

Critical Role of Endoplasmic Reticulum Stress in Chronic Intermittent Hypoxia-Induced Deficits in Synaptic Plasticity and Long-Term Memory.

Science.gov (United States)

Xu, Lin-Hao; Xie, Hui; Shi, Zhi-Hui; Du, Li-Da; Wing, Yun-Kwok; Li, Albert M; Ke, Ya; Yung, Wing-Ho

2015-09-20

This study examined the role of endoplasmic reticulum (ER) stress in mediating chronic intermittent hypoxia (IH)-induced neurocognitive deficits. We designed experiments to demonstrate that ER stress is initiated in the hippocampus under chronic IH and determined its role in apoptotic cell death, impaired synaptic structure and plasticity, and memory deficits. Two weeks of IH disrupted ER fine structure and upregulated ER stress markers, glucose-regulated protein 78, caspase-12, and C/EBP homologous protein, in the hippocampus, which could be suppressed by ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid. Meanwhile, ER stress induced apoptosis via decreased Bcl-2, promoted reactive oxygen species production, and increased malondialdehyde formation and protein carbonyl, as well as suppressed mitochondrial function. These effects were largely prevented by ER stress inhibitors. On the other hand, suppression of oxidative stress could reduce ER stress. In addition, the length of the synaptic active zone and number of mature spines were reduced by IH. Long-term recognition memory and spatial memory were also impaired, which was accompanied by reduced long-term potentiation in the Schaffer collateral pathway. These effects were prevented by coadministration of the TUDCA. These results show that ER stress plays a critical role in underlying memory deficits in obstructive sleep apnea (OSA)-associated IH. Attenuators of ER stress may serve as novel adjunct therapeutic agents for ameliorating OSA-induced neurocognitive impairment.

Endomembrane Ca2+-AtPases play a significant role in virus-induced adaptation to oxidative stress

DEFF Research Database (Denmark)

Shabala, Sergey; Bækgaard, Lone; Shabala, Lana

2011-01-01

Although the role of Ca2+ influx channels in oxidative stress signaling and cross-tolerance in plants is well established, little is known about the role of active Ca2+ efflux systems in this process. In our recent paper,17 we reported Potato Virus X (PVX)-induced acquired resistance to oxidative...... in adaptive responses to oxidative stress by removing excessive Ca2+ from the cytosol, and that their functional expression is significantly altered in PVX-inoculated plants. These findings highlight the crucial role of Ca2+ efflux systems in acquired tolerance to oxidative stress and open up prospects...... stress in Nicotiana benthamiana and showed the critical role of plasma membrane Ca2+/H+ exchangers in this process. The current study continues this research. Using biochemical and electrophysiological approaches, we reveal that both endomembrane P2A and P2B Ca2+-ATPases play significant roles...

Critical role of aldehydes in cigarette smoke-induced acute airway inflammation

NARCIS (Netherlands)

van der Toorn, Marco; Slebos, Dirk-Jan; de Bruin, Harold G.; Gras, Renee; Rezayat, Delaram; Jorge, Lucie; Sandra, Koen; van Oosterhout, Antoon J. M.

2013-01-01

Background: Cigarette smoking (CS) is the most important risk factor for COPD, which is associated with neutrophilic airway inflammation. We hypothesize, that highly reactive aldehydes are critical for CS-induced neutrophilic airway inflammation. Methods: BALB/c mice were exposed to CS, water

The Critical Role of Positive Incentives for Reducing Insider Threats

Science.gov (United States)

2016-12-01

such skills . Creating a technical track of advancement separate from the management track can help ameliorate these problems. Effective Communication ...Omar, F.; Halim, F. W.; & Hafidz, S. W. M. The Mediating Role of Organizational- Based Self - Esteem in Perceived Organizational Support and... Esteem Relate to Deviant Behavior? The Role of Contingencies of Self -Worth. Journal of Applied Psychology. Volume 94. Number 5. September 2009. Page

Understanding ironic criticism and empathic praise: The role of emotive communication.

Science.gov (United States)

Agostino, Alba; Im-Bolter, Nancie; Stefanatos, Arianna K; Dennis, Maureen

2017-06-01

Ironic criticism and empathic praise are forms of social communication that influence the affective states of others in a negative or positive way. In a sample of 76 typically developing children and adolescents (mean age = 11 years; 4 months; SD: 2 years; 8 months), we studied how understanding of emotional expression (facial expression of emotion) and emotive communication (affective theory of mind) was related to the ability to understand negatively valenced ironic criticism and positively valenced empathic praise. We modelled comprehension of irony and empathy in school-aged children in relation to age and understanding of emotional expression and emotive communication. As expected, children showed significantly better understanding of emotional expression than emotive communication, which requires understanding why someone might mask their inner emotions. Meditational analyses showed that emotive communication partially mediated the relation between age and understanding ironic criticism and empathic praise. These findings suggest that the development of understanding irony and empathy over the school-age years is associated with affective attributions or affective theory of mind. Statement of contribution What is already known on this subject? Theory of mind has been found to be related to the developmental understanding of social communication. Correct interpretation of facial emotional cues is also important for interpreting social communication. What does this study add? Affective components (i.e., affective theory of mind) also contribute to the development of social communication. Emotive communication, the ability to modulate one's emotional expression according to social display rules may be predictive of social communication competency. © 2016 The British Psychological Society.

Chronic Student Absenteeism: The Critical Role of School Nurses.

Science.gov (United States)

Jacobsen, Kathleen; Meeder, Linda; Voskuil, Vicki R

2016-05-01

Routine school attendance is necessary for youth to develop into well-educated, successful adult citizens who will make significant contributions to society. Yet over 5 million students in the United States are chronically absent missing more than 10% of school in a year. The growing problem of chronic absenteeism among youth can be linked to increases in chronic health conditions in childhood such as allergies, asthma, diabetes, and obesity. School nurses are in an ideal position to play a vital role in reducing chronic student absenteeism, enabling youth to achieve their maximum learning potential. However, the role of the school nurse has not historically been recognized as a key factor for assisting youth to be present and regularly engaged in school. This feature article highlights a hospital-funded school nurse program within the state of Michigan that has reduced chronic absenteeism rates by placing school nurses into schools where previously there were none. The program implemented a number of initiatives that were instrumental in increasing the health and safety of students and provides a unique "before and after" glimpse of how school nursing reduces chronic student absenteeism rates and validates the essential role of the nurse within the educational system. © 2016 The Author(s).

The influence of strain introduced by differential thermal contraction on the critical current of Nb3Sn supercontractors

International Nuclear Information System (INIS)

Pasztor, G.; Jakob, B.

1992-01-01

The NET Team initiated in 1988 a development program for a high current cable-in-conduit superconductor planned for fusion magnets. The basic strand chosen for the cable was a Nb 3 Sn wire of TWCA made by the MJR method. The electrical testing of the stand and sub-cables was carried out at several European Laboratories including PSI (Paul Scherrer Institute). The inter-laboratory comparison of the results revealed large differences in the measured critical currents of the strands. Obviously, each laboratory performed the measurement of critical current in its own way, and as a result some discrepancies in the measured values were inevitable. No standard technique of measuring critical current has been developed for Nb 3 Sn wires. The main source of difficulty arises from the strain sensitivity of Nb 3 Sn. It has been shown that the sample holder material and geometry as well as the bonding method of the specimen to its holder have important effects on the critical current measurements. It was found recently that the reaction mandrel material significantly influences the current-carrying capacity of Nb 3 Sn wires. The aim of this paper is to improve current understanding of the effect of sample configuration on critical current in Nb 3 Sn multifilamentary wires. The present study confirms the important role of reaction mandrel material on critical current. Based on comparative critical current measurements of straight and coil samples, an attempt is made to find the sample configuration which eliminates the strain induced in the specimen

Critical Theory and Political Socialization

Directory of Open Access Journals (Sweden)

SIK, Domonkos

2014-12-01

Full Text Available The paper explores the relevance of critical theories of modernity in the research of memory transmission and political socialization. Firstly, the relevant concepts of Habermas, Giddens and Bourdieu are overviewed. Secondly, the notion of political culture and memory transmission are reinterpreted from the perspective of these theories, revealing different sources and forms of radicalism. Finally, divergent constellations of modernization are reintroduced as the broadest context of the processes of political formation.

Giant Magnetic Fluctuations at the Critical Endpoint in Insulating HoMnO3

Science.gov (United States)

Choi, Y. J.; Lee, N.; Sharma, P. A.; Kim, S. B.; Vajk, O. P.; Lynn, J. W.; Oh, Y. S.; Cheong, S.-W.

2013-04-01

Although abundant research has focused recently on the quantum criticality of itinerant magnets, critical phenomena of insulating magnets in the vicinity of critical endpoints (CEP’s) have rarely been revealed. Here we observe an emergent CEP at 2.05 T and 2.2 K with a suppressed thermal conductivity and concomitant strong critical fluctuations evident via a divergent magnetic susceptibility (e.g., χ''(2.05T,2.2K)/χ''(3T,2.2K)≈23,500%, comparable to the critical opalescence in water) in the hexagonal insulating antiferromagnet HoMnO3.

Comparative Analysis of WUSCHEL-Related Homeobox Genes Revealed Their Parent-of-Origin and Cell Type-Specific Expression Pattern During Early Embryogenesis in Tobacco

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Xuemei Zhou

2018-03-01

Full Text Available WUSCHEL-related homeobox (WOX gene is a plant-specific clade of homeobox transcription factors. Increasing evidences reveal that WOXs play critical roles in early embryogenesis, which involves zygote development, initiation of zygote division, and apical or basal cell lineage establishment. However, how WOXs regulate these developmental events remains largely unknown, and even detailed expression pattern in gametes and early proembryos is not yet available. Here, 13 WOX family genes were identified in Nicotiana tabacum genome. Comparative analysis of 13 WOX family genes with their homologs in Arabidopsis thaliana reveals relatively conserved expression pattern of WUS and WOX5 in shoot/root apical meristem. Whereas variations were also found, e.g., lacking homolog of WOX8 (a marker for suspensor cell in tobacco genome and the expression of WOX2/WOX9 in both apical cell and basal cell. Transient transcriptional activity analysis revealed that WOXs in WUS clade have repressive activities for their target's transcription, whereas WOXs in ancient and intermediate clade have activation activities, giving a molecular basis for the phylogenetic classification of tobacco WOXs into three major clades. Expression pattern analysis revealed that some WOXs (e.g., WOX 13a expressed in both male and female gametes and some WOXs (e.g., WOX 11 and WOX 13b displayed the characteristics of parent-of-origin genes. Interestingly, some WOXs (e.g., WOX2 and WOX9, which are essential for early embryo patterning, were de novo transcribed in zygote, indicating relevant mechanism for embryo pattern formation is only established in zygote right after fertilization and not carried in by gametes. We also found that most WOXs displayed a stage-specific and cell type-specific expression pattern. Taken together, this work provides a detailed landscape of WOXs in tobacco during fertilization and early embryogenesis, which will facilitate the understanding of their specific roles

Beneficial effects of vitamin C and vitamin E on reserpine-induced oral dyskinesia in rats: critical role of striatal catalase activity.

Science.gov (United States)

Faria, Rulian Ricardo; Abílio, Vanessa Costhek; Grassl, Christian; Chinen, Cibele Cristina; Negrão, Luciana Takahashi Ribeiro; de Castro, Juliana Pedroso Moraes Vilela; Fukushiro, Daniela Fukue; Rodrigues, Marcelo Scarpari Dutra; Gomes, Patricia Helena Zanier; Registro, Sibele; de Carvalho, Rita de Cassia; D'Almeida, Vania; Silva, Regina Helena; Ribeiro, Rosana de Alencar; Frussa-Filho, Roberto

2005-06-01

Oral dyskinesias are implicated in a series of neuropathologies and have been associated to an increase in oxidative stress. Several antioxidants, including vitamin E, decrease reserpine-induced oral dyskinesia (OD) in rodents and we have described a protective role of striatal catalase against the development of OD. The aim of this study was to verify the effects of vitamin C alone or in combination with vitamin E on reserpine-induced OD as well as to determine a possible role of catalase in the antidyskinetic property of these vitamins. Different doses of vitamin C attenuated reserpine-induced increase in OD. A similar treatment with an effective dose of vitamin C concomitant to an effective dose of vitamin E potentiated the antidyskinetic effect of both vitamins when administered alone. The administration of these vitamins alone produced an increase in striatal catalase activity that likewise was potentiated by their combined administration. In addition, the antidyskinetic property of vitamin E and vitamin C was abolished by a concomitant treatment with the catalase inhibitor aminotriazole. These results indicate a beneficial effect of these vitamins and reinforce the critical role of striatal catalase against the development of oral dyskinesias.

Messy Problems and Lay Audiences: Teaching Critical Thinking within the Finance Curriculum

Science.gov (United States)

Carrithers, David; Ling, Teresa; Bean, John C.

2008-01-01

This article investigates the critical thinking difficulties of finance majors when asked to address ill-structured finance problems. The authors build on previous research in which they asked students to analyze an ill-structured investment problem and recommend a course of action. The results revealed numerous critical thinking weaknesses,…

On the prospects of increasing critical parameters of superconductors

International Nuclear Information System (INIS)

Lazarev, B.G.; Pan, V.M.

1979-01-01

Noted is the importance of the production of materials with high critical parameters for modern science and technology. Considered are present notions about the nature of high critical densities of critical current. The opinion is expressed that the search of most high-temperature and high-field superconductors should be carried out, in the first place, among compounds based on transition metals displaying structural instability. Noted are prospects of the work over the synthesis of metastabile compounds with A15 structure (e.g. Nb 3 Si), three-component and more complex compounds, and superconductive amorphous systems(metglasses). It is emphasized that the exceeding of the paramagnetic limit of the critical magnetic field is often observed experimentally, and the prospects of critical field increase are sufficiently favourable. Considered is the role of narrow current channels in the formation of critical current density of superconductors

Teaching Critical Thinking in Undergraduate Science Courses.

Science.gov (United States)

Hager, Paul; Sleet, Ray; Logan, Peter; Hooper, Mal

2003-01-01

Explains the design and evaluation of a project aimed at fostering the critical thinking abilities and dispositions of first year students at an Australian university. Most of the tasks relate to applications of chemistry and physics in everyday life. Many students revealed that their thinking skills were enhanced by their experience in attempting…

Fungi contribute critical but spatially varying roles in nitrogen and carbon cycling in acid mine drainage

Directory of Open Access Journals (Sweden)

Annika C. Mosier

2016-03-01

Full Text Available The ecosystem roles of fungi have been extensively studied by targeting one organism and/or biological process at a time, but the full metabolic potential of fungi has rarely been captured in an environmental context. We hypothesized that fungal genome sequences could be assembled directly from the environment using metagenomics and that transcriptomics and proteomics could simultaneously reveal metabolic differentiation across habitats. We reconstructed the near-complete 27 Mbp genome of a filamentous fungus, Acidomyces richmondensis, and evaluated transcript and protein expression in floating and streamer biofilms from an acid mine drainage system. A. richmondensis transcripts involved in denitrification and in the degradation of complex carbon sources (including cellulose were up-regulated in floating biofilms, whereas central carbon metabolism and stress-related transcripts were significantly up-regulated in streamer biofilms. These findings suggest that the biofilm niches are distinguished by distinct carbon and nitrogen resource utilization, oxygen availability and environmental challenges. An isolated A. richmondensis strain from this environment was used to validate the metagenomics-derived genome and confirm nitrous oxide production at pH 1. Overall, our analyses defined mechanisms of fungal adaptation and identified a functional shift related to different roles in carbon and nitrogen turnover for the same species of fungi growing in closely located but distinct biofilm niches.

Comparative genome analysis of Megasphaera sp. reveals niche specialization and its potential role in the human gut.

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Sudarshan Anand Shetty

Full Text Available With increasing number of novel bacteria being isolated from the human gut ecosystem, there is a greater need to study their role in the gut ecosystem and their effect on the host health. In the present study, we carried out in silico genome-wide analysis of two novel Megasphaera sp. isolates NM10 (DSM25563 and BL7 (DSM25562, isolated from feces of two healthy individuals and validated the key features by in vitro studies. The analysis revealed the general metabolic potential, adaptive features and the potential effects of these isolates on the host. The comparative genome analysis of the two human gut isolates NM10 and BL7 with ruminal isolate Megasphaera elsdenii (DSM20460 highlighted the differential adaptive features for their survival in human gut. The key findings include features like bile resistance, presence of various sensory and regulatory systems, stress response systems, membrane transporters and resistance to antibiotics. Comparison of the "glycobiome" based on the genomes of the ruminal isolate with the human gut isolates NM10 and BL revealed the presence of diverse and unique sets of Carbohydrate-Active enzymes (CAZymes amongst these isolates, with a higher collection of CAZymes in the human gut isolates. This could be attributed to the difference in host diet and thereby the environment, consequently suggesting host specific adaptation in these isolates. In silico analysis of metabolic potential predicted the ability of these isolates to produce important metabolites like short chain fatty acids (butyrate, acetate, formate, and caproate, vitamins and essential amino acids, which was further validated by in vitro experiments. The ability of these isolates to produce important metabolites advocates for a potential healthy influence on the host. Further in vivo studies including transcriptomic and proteomic analysis will be required for better understanding the role and impact of these Megasphaera sp. isolates NM10 and BL7 on the

Elucidation of the regulatory role of the fructose operon reveals a novel target for enhancing the NADPH supply in Corynebacterium glutamicum

DEFF Research Database (Denmark)

Wang, Zhihao; Chan, Siu Hung Joshua; Sudarsan, Suresh

2016-01-01

is linked to redox and to the general metabolism. We here provide new insights into the regulation of the metabolism of this important platform organism by systematically characterizing mutants carrying various lesions in the fructose operon. Initially, we found that a strain where the dedicated fructose...... uptake system had been inactivated (KO-ptsF) was hampered in growth on sucrose minimal medium, and suppressor mutants appeared readily. Comparative genomic analysis in conjunction with enzymatic assays revealed that suppression was linked to inactivation of the pfkB gene, encoding a fructose-1-phosphate...... kinase. Detailed characterization of KO-ptsF, KO-pfkB and double knock-out (DKO) derivatives revealed a strong role for sugar-phosphates, especially fructose-1-phosphate (F1P), in governing sugar as well as redox metabolism due to effects on transcriptional regulation of key genes. These findings allowed...

Long-Term Live Cell Imaging Reveals New Roles For Salmonella Effector Proteins SseG and SteA

Science.gov (United States)

McQuate, Sarah E.; Young, Alexandra M.; Silva-Herzog, Eugenia; Bunker, Eric; Hernandez, Mateo; de Chaumont, Fabrice; Liu, Xuedong; Detweiler, Corrella S.; Palmer, Amy E.

2016-01-01

Summary Salmonella Typhimurium is an intracellular bacterial pathogen that infects both epithelial cells and macrophages. Salmonella effector proteins, which are translocated into the host cell and manipulate host cell components, control the ability to replicate and/or survive in host cells. Due to the complexity and heterogeneity of Salmonella infections, there is growing recognition of the need for single cell and live-cell imaging approaches to identify and characterize the diversity of cellular phenotypes and how they evolve over time. Here we establish a pipeline for long-term (16 hours) live-cell imaging of infected cells and subsequent image analysis methods. We apply this pipeline to track bacterial replication within the Salmonella-containing vacuole in epithelial cells, quantify vacuolar replication versus survival in macrophages, and investigate the role of individual effector proteins in mediating these parameters. This approach revealed that dispersed bacteria can coalesce at later stages of infection, that the effector protein SseG influences the propensity for cytosolic hyperreplication in epithelial cells, and that while SteA only has a subtle effect on vacuolar replication in epithelial cells, it has a profound impact on infection parameters in immunocompetent macrophages, suggesting differential roles for effector proteins in different infection models. PMID:27376507

Thinking Critically about Critical Thinking

Science.gov (United States)

Mulnix, Jennifer Wilson

2012-01-01

As a philosophy professor, one of my central goals is to teach students to think critically. However, one difficulty with determining whether critical thinking can be taught, or even measured, is that there is widespread disagreement over what critical thinking actually is. Here, I reflect on several conceptions of critical thinking, subjecting…

Unintended targeting of Dmp1-Cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice.

Science.gov (United States)

Lim, Joohyun; Burclaff, Joseph; He, Guangxu; Mills, Jason C; Long, Fanxin

2017-01-01

Cre/loxP technology has been widely used to study cell type-specific functions of genes. Proper interpretation of such data critically depends on a clear understanding of the tissue specificity of Cre expression. The Dmp1-Cre mouse, expressing Cre from a 14-kb DNA fragment of the mouse Dmp1 gene, has become a common tool for studying gene function in osteocytes, but the presumed cell specificity is yet to be fully established. By using the Ai9 reporter line that expresses a red fluorescent protein upon Cre recombination, we find that in 2-month-old mice, Dmp1-Cre targets not only osteocytes within the bone matrix but also osteoblasts on the bone surface and preosteoblasts at the metaphyseal chondro-osseous junction. In the bone marrow, Cre activity is evident in certain stromal cells adjacent to the blood vessels, but not in adipocytes. Outside the skeleton, Dmp1-Cre marks not only the skeletal muscle fibers, certain cells in the cerebellum and the hindbrain but also gastric and intestinal mesenchymal cells that express Pdgfra . Confirming the utility of Dmp1-Cre in the gastrointestinal mesenchyme, deletion of Bmpr1a with Dmp1-Cre causes numerous large polyps along the gastrointestinal tract, consistent with prior work involving inhibition of BMP signaling. Thus, caution needs to be exercised when using Dmp1-Cre because it targets not only the osteoblast lineage at an earlier stage than previously appreciated, but also a number of non-skeletal cell types.

In vivo RNAi screen reveals neddylation genes as novel regulators of Hedgehog signaling.

Directory of Open Access Journals (Sweden)

Juan Du

Full Text Available Hedgehog (Hh signaling is highly conserved in all metazoan animals and plays critical roles in many developmental processes. Dysregulation of the Hh signaling cascade has been implicated in many diseases, including cancer. Although key components of the Hh pathway have been identified, significant gaps remain in our understanding of the regulation of individual Hh signaling molecules. Here, we report the identification of novel regulators of the Hh pathway, obtained from an in vivo RNA interference (RNAi screen in Drosophila. By selectively targeting critical genes functioning in post-translational modification systems utilizing ubiquitin (Ub and Ub-like proteins, we identify two novel genes (dUba3 and dUbc12 that negatively regulate Hh signaling activity. We provide in vivo and in vitro evidence illustrating that dUba3 and dUbc12 are essential components of the neddylation pathway; they function in an enzyme cascade to conjugate the ubiquitin-like NEDD8 modifier to Cullin proteins. Neddylation activates the Cullin-containing ubiquitin ligase complex, which in turn promotes the degradation of Cubitus interruptus (Ci, the downstream transcription factor of the Hh pathway. Our study reveals a conserved molecular mechanism of the neddylation pathway in Drosophila and sheds light on the complex post-translational regulations in Hh signaling.

Structural Insight into the Critical Role of the N-Terminal Region in the Catalytic Activity of Dual-Specificity Phosphatase 26.

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Eun-Young Won

Full Text Available Human dual-specificity phosphatase 26 (DUSP26 is a novel target for anticancer therapy because its dephosphorylation of the p53 tumor suppressor regulates the apoptosis of cancer cells. DUSP26 inhibition results in neuroblastoma cell cytotoxicity through p53-mediated apoptosis. Despite the previous structural studies of DUSP26 catalytic domain (residues 61-211, DUSP26-C, the high-resolution structure of its catalytically active form has not been resolved. In this study, we determined the crystal structure of a catalytically active form of DUSP26 (residues 39-211, DUSP26-N with an additional N-terminal region at 2.0 Å resolution. Unlike the C-terminal domain-swapped dimeric structure of DUSP26-C, the DUSP26-N (C152S monomer adopts a fold-back conformation of the C-terminal α8-helix and has an additional α1-helix in the N-terminal region. Consistent with the canonically active conformation of its protein tyrosine phosphate-binding loop (PTP loop observed in the structure, the phosphatase assay results demonstrated that DUSP26-N has significantly higher catalytic activity than DUSP26-C. Furthermore, size exclusion chromatography-multiangle laser scattering (SEC-MALS measurements showed that DUSP26-N (C152S exists as a monomer in solution. Notably, the crystal structure of DUSP26-N (C152S revealed that the N-terminal region of DUSP26-N (C152S serves a scaffolding role by positioning the surrounding α7-α8 loop for interaction with the PTP-loop through formation of an extensive hydrogen bond network, which seems to be critical in making the PTP-loop conformation competent for phosphatase activity. Our study provides the first high-resolution structure of a catalytically active form of DUSP26, which will contribute to the structure-based rational design of novel DUSP26-targeting anticancer therapeutics.

Combined Transcriptomic Analysis Revealed AKR1B10 Played an Important Role in Psoriasis through the Dysregulated Lipid Pathway and Overproliferation of Keratinocyte

Directory of Open Access Journals (Sweden)

Yunlu Gao

2017-01-01

Full Text Available RNA-seq has enabled in-depth analysis of the pathogenesis of psoriasis on the transcriptomic level, and many biomarkers have been discovered to be related to the immune response, lipid metabolism, and keratinocyte proliferation. However, few studies have combined analysis from various datasets. In this study, we integrated different psoriasis RNA-seq datasets to reveal the pathogenesis of psoriasis through the analysis of differentially expressed genes (DEGs, pathway analysis, and functional annotation. The revealed biomarkers were further validated through proliferation phenotypes. The results showed that DEGs were functionally related to lipid metabolism and keratinocyte differentiation dysregulation. The results also showed new biomarkers, such as AKR1B10 and PLA2G gene families, as well as pathways that include the PPAR signaling pathway, cytokine-cytokine receptor interaction, alpha-linoleic acid metabolism, and glycosphingolipid biosynthesis. Using siRNA knockdown assays, we further validated the role that the AKR1B10 gene plays in proliferation. Our study demonstrated not only the dysfunction of the AKR1B10 gene in lipid metabolizing but also its important role in the overproliferation and migration of keratinocyte, which provided evidence for further therapeutic uses for psoriasis.

Critical role of climate change in plant selection and millet domestication in North China.

Science.gov (United States)

Yang, Xiaoyan; Wu, Wenxiang; Perry, Linda; Ma, Zhikun; Bar-Yosef, Ofer; Cohen, David J; Zheng, Hongbo; Ge, Quansheng

2018-05-18

While North China is one of the earliest independent centers for cereal domestication in the world, the earliest stages of the long process of agricultural origins remain unclear. While only millets were eventually domesticated in early sedentary societies there, recent archaeobotanical evidence reported here indicates that grasses from the Paniceae (including millets) and Triticeae tribes were exploited together by foraging groups from the Last Glacial Maximum to the mid-Holocene. Here we explore how and why millets were selected for domestication while Triticeae were abandoned. We document the different exploitation and cultivation trajectories of the two tribes employing ancient starch data derived from nine archaeological sites dating from 25,000 to 5500 cal BP (LGM through mid-Holocene) in North China. With this diachronic overview, we can place the trajectories into the context of paleoclimatic reconstructions for this period. Entering the Holocene, climatic changes increased the yield stability, abundance, and availability of the wild progenitors of millets, with growing conditions increasingly favoring millets while becoming more unfavorable for grasses of the Triticeae tribe. We thus hypothesize that climate change played a critical role in the selection of millet species for domestication in North China, with early domestication evidenced by 8700 cal BP.

a model for the determination of the critical buckling load of self

African Journals Online (AJOL)

HP

Considering the widespread use of this type of structure and the critical role it ... proposed by the model for the critical buckling load of self- supporting lattice tower, whose equivalent solid beam- ... stiffness, both material and geometric, [5, 6].

Critical Care nurses' understanding of the NHS knowledge and skills framework. An interpretative phenomenological analysis.

Science.gov (United States)

Stewart, Laura F M; Rae, Agnes M

2013-01-01

This small-scale research study aimed to explore Critical Care nurses' understanding of the National Health Service (NHS) Knowledge and Skills Framework (KSF) in relationship to its challenges and their nursing role. The NHS KSF is central to the professional development of nurses in Critical Care and supports the effective delivery of health care in the UK. KSF was implemented in 2004 yet engagement seems lacking with challenges often identified. This qualitative study adopted an Interpretative Phenomenological Analysis framework. Data were collected from five Critical Care nurses using semi-structured interviews that were transcribed for analysis. Two super-ordinate themes of 'engagement' and 'theory-practice gap' were identified. Six subthemes of 'fluency', 'transparency', 'self-assessment', 'achieving for whom', 'reflection' and 'the nursing role' further explained the super-ordinate themes. Critical Care nurses demonstrated layers of understanding about KSF. Challenges identified were primarily concerned with complex language, an unclear process and the use of reflective and self-assessment skills. Two theory-practice gaps were found. Critical Care nurses understood the principles of KSF but they either did not apply or did not realize they applied these principles. They struggled to relate KSF to Critical Care practice and felt it did not capture the 'essence' of their nursing role in Critical Care. Recommendations were made for embedding KSF into Critical Care practice, using education and taking a flexible approach to KSF to support the development and care delivery of Critical Care nurses. © 2012 The Authors. Nursing in Critical Care © 2012 British Association of Critical Care Nurses.

Mechanisms of self-organized criticality in social processes of knowledge creation.

Science.gov (United States)

Tadić, Bosiljka; Dankulov, Marija Mitrović; Melnik, Roderick

2017-09-01

In online social dynamics, a robust scale invariance appears as a key feature of collaborative efforts that lead to new social value. The underlying empirical data thus offers a unique opportunity to study the origin of self-organized criticality (SOC) in social systems. In contrast to physical systems in the laboratory, various human attributes of the actors play an essential role in the process along with the contents (cognitive, emotional) of the communicated artifacts. As a prototypical example, we consider the social endeavor of knowledge creation via Questions and Answers (Q&A). Using a large empirical data set from one of such Q&A sites and theoretical modeling, we reveal fundamental characteristics of SOC by investigating the temporal correlations at all scales and the role of cognitive contents to the avalanches of the knowledge-creation process. Our analysis shows that the universal social dynamics with power-law inhomogeneities of the actions and delay times provides the primary mechanism for self-tuning towards the critical state; it leads to the long-range correlations and the event clustering in response to the external driving by the arrival of new users. In addition, the involved cognitive contents (systematically annotated in the data and observed in the model) exert important constraints that identify unique classes of the knowledge-creation avalanches. Specifically, besides determining a fine structure of the developing knowledge networks, they affect the values of scaling exponents and the geometry of large avalanches and shape the multifractal spectrum. Furthermore, we find that the level of the activity of the communities that share the knowledge correlates with the fluctuations of the innovation rate, implying that the increase of innovation may serve as the active principle of self-organization. To identify relevant parameters and unravel the role of the network evolution underlying the process in the social system under consideration, we

Mechanisms of self-organized criticality in social processes of knowledge creation

Science.gov (United States)

Tadić, Bosiljka; Dankulov, Marija Mitrović; Melnik, Roderick

2017-09-01

In online social dynamics, a robust scale invariance appears as a key feature of collaborative efforts that lead to new social value. The underlying empirical data thus offers a unique opportunity to study the origin of self-organized criticality (SOC) in social systems. In contrast to physical systems in the laboratory, various human attributes of the actors play an essential role in the process along with the contents (cognitive, emotional) of the communicated artifacts. As a prototypical example, we consider the social endeavor of knowledge creation via Questions and Answers (Q&A). Using a large empirical data set from one of such Q&A sites and theoretical modeling, we reveal fundamental characteristics of SOC by investigating the temporal correlations at all scales and the role of cognitive contents to the avalanches of the knowledge-creation process. Our analysis shows that the universal social dynamics with power-law inhomogeneities of the actions and delay times provides the primary mechanism for self-tuning towards the critical state; it leads to the long-range correlations and the event clustering in response to the external driving by the arrival of new users. In addition, the involved cognitive contents (systematically annotated in the data and observed in the model) exert important constraints that identify unique classes of the knowledge-creation avalanches. Specifically, besides determining a fine structure of the developing knowledge networks, they affect the values of scaling exponents and the geometry of large avalanches and shape the multifractal spectrum. Furthermore, we find that the level of the activity of the communities that share the knowledge correlates with the fluctuations of the innovation rate, implying that the increase of innovation may serve as the active principle of self-organization. To identify relevant parameters and unravel the role of the network evolution underlying the process in the social system under consideration, we

Characterization of a null allelic mutant of the rice NAL1 gene reveals its role in regulating cell division.

Directory of Open Access Journals (Sweden)

Dan Jiang

Full Text Available Leaf morphology is closely associated with cell division. In rice, mutations in Narrow leaf 1 (NAL1 show narrow leaf phenotypes. Previous studies have shown that NAL1 plays a role in regulating vein patterning and increasing grain yield in indica cultivars, but its role in leaf growth and development remains unknown. In this report, we characterized two allelic mutants of NARROW LEAF1 (NAL1, nal1-2 and nal1-3, both of which showed a 50% reduction in leaf width and length, as well as a dwarf culm. Longitudinal and transverse histological analyses of leaves and internodes revealed that cell division was suppressed in the anticlinal orientation but enhanced in the periclinal orientation in the mutants, while cell size remained unaltered. In addition to defects in cell proliferation, the mutants showed abnormal midrib in leaves. Map-based cloning revealed that nal1-2 is a null allelic mutant of NAL1 since both the whole promoter and a 404-bp fragment in the first exon of NAL1 were deleted, and that a 6-bp fragment was deleted in the mutant nal1-3. We demonstrated that NAL1 functions in the regulation of cell division as early as during leaf primordia initiation. The altered transcript level of G1- and S-phase-specific genes suggested that NAL1 affects cell cycle regulation. Heterogeneous expression of NAL1 in fission yeast (Schizosaccharomyces pombe further supported that NAL1 affects cell division. These results suggest that NAL1 controls leaf width and plant height through its effects on cell division.

Spontaneous Formation of Nanopillar Arrays in Ultrathin Viscous Films: Critical Role of Thermocapillary Stresses

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Troian, Sandra; Dietzel, Mathias

2010-03-01

Nanoscale structures manifest exceedingly large surface to volume ratios and are therefore highly susceptible to control by surface stresses. Actuation techniques which can exploit this feature provide a key strategy for construction and self-organization of large area arrays. During the past decade, several groups have reported that molten polymer nanofilms subject to an ultra-large transverse thermal gradient undergo spontaneous formation of nanopillar arrays. The prevailing explanation is that coherent interfacial reflection of acoustic phonons causes periodic modulation of the radiation pressure leading to instability and pillar growth. We demonstrate instead that thermocapillary forces play a crucial if not dominant role in the formation process due to the strong modulation of surface tension with temperature. Any nanoscale viscous film is prone to such formations, not just polymeric films. Analysis of the governing interface equation reveals the mechanism controlling the growth, spacing and symmetry of these self-assembling arrays. We discuss how these findings are being used in our laboratory to construct nanoscale components for optical and photonic applications.

Critical psychology: A geography of intellectual engagement and resistance.

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Teo, Thomas

2015-04-01

Critical psychology has become a generative and international movement in the last 5 decades, with self-identifying critical psychologists emerging from around the globe with publications and contributions, both theoretical and practical, in many areas of psychology. This article provides an overview of current trends in critical psychology and elucidates historical sources and theoretical tenets. Presented are the relationship between individual subjectivity and society, the role of power in the discipline, the problem of subjectification, the importance of reflexivity and intersubjectivity in the context of research practices, methodologies of change for different contexts, and the ethical-political positions from which critical psychologists operate. Challenges to critical psychology, which include engagements with indigenous psychologies, new forms of internationalization, and advancing transdisciplinary work, are discussed. (c) 2015 APA, all rights reserved).

Genome-wide mouse mutagenesis reveals CD45-mediated T cell function as critical in protective immunity to HSV-1.

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Grégory Caignard

2013-09-01

Full Text Available Herpes simplex encephalitis (HSE is a lethal neurological disease resulting from infection with Herpes Simplex Virus 1 (HSV-1. Loss-of-function mutations in the UNC93B1, TLR3, TRIF, TRAF3, and TBK1 genes have been associated with a human genetic predisposition to HSE, demonstrating the UNC93B-TLR3-type I IFN pathway as critical in protective immunity to HSV-1. However, the TLR3, UNC93B1, and TRIF mutations exhibit incomplete penetrance and represent only a minority of HSE cases, perhaps reflecting the effects of additional host genetic factors. In order to identify new host genes, proteins and signaling pathways involved in HSV-1 and HSE susceptibility, we have implemented the first genome-wide mutagenesis screen in an in vivo HSV-1 infectious model. One pedigree (named P43 segregated a susceptible trait with a fully penetrant phenotype. Genetic mapping and whole exome sequencing led to the identification of the causative nonsense mutation L3X in the Receptor-type tyrosine-protein phosphatase C gene (Ptprc(L3X, which encodes for the tyrosine phosphatase CD45. Expression of MCP1, IL-6, MMP3, MMP8, and the ICP4 viral gene were significantly increased in the brain stems of infected Ptprc(L3X mice accounting for hyper-inflammation and pathological damages caused by viral replication. Ptprc(L3X mutation drastically affects the early stages of thymocytes development but also the final stage of B cell maturation. Transfer of total splenocytes from heterozygous littermates into Ptprc(L3X mice resulted in a complete HSV-1 protective effect. Furthermore, T cells were the only cell population to fully restore resistance to HSV-1 in the mutants, an effect that required both the CD4⁺ and CD8⁺ T cells and could be attributed to function of CD4⁺ T helper 1 (Th1 cells in CD8⁺ T cell recruitment to the site of infection. Altogether, these results revealed the CD45-mediated T cell function as potentially critical for infection and viral spread to the

Flood vulnerability of critical infrastructure in Cork, Ireland

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de Bruijn Karin M.

2016-01-01

Full Text Available Recent flood events in Ireland and particularly in County Cork have caused significant disruption to health service provisions, interruption of water and power supplies, and damage to roads and other transportation infrastructure, affecting the lives of hundreds of thousands of people over a prolonged period of weeks. These events clearly reveal- the vulnerability of the critical infrastructure to flooding and the dependence of society on critical infrastructure. In order to reduce the flood vulnerability and increase the resilience of the critical infrastructure networks in the future, detailed evidence-based analysis and assessment is essential. To this end a case study has been carried out on Cork City which analyses this vulnerability as it was in 2009, and as it is currently, and identifies adaptation options to reduce the future vulnerability of critical infrastructure to flooding and to build a more resilient society. This paper describes the storyline approach and CIrcle tool and their application to Cork City which focused on the analysis of the flood vulnerability of critical infrastructure and the impacts of failure of the infrastructure for other critical functions and on society.

Critical care medicine as a distinct product line with substantial financial profitability: the role of business planning.

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Bekes, Carolyn E; Dellinger, R Phillip; Brooks, Daniel; Edmondson, Robert; Olivia, Christopher T; Parrillo, Joseph E

2004-05-01

As academic health centers face increasing financial pressures, they have adopted a more businesslike approach to planning, particularly for discrete "product" or clinical service lines. Since critical care typically has been viewed as a service provided by a hospital, and not a product line, business plans have not historically been developed to expand and promote critical care. The major focus when examining the finances of critical care has been cost reduction, not business development. We hypothesized that a critical care business plan can be developed and analyzed like other more typical product lines and that such a critical care product line can be profitable for an institution. In-depth analysis of critical care including business planning for critical care services. Regional academic health center in southern New Jersey. None. As part of an overall business planning process directed by the Board of Trustees, the critical care product line was identified by isolating revenue, expenses, and profitability associated with critical care patients. We were able to identify the major sources ("value chain") of critical care patients: the emergency room, patients who are admitted for other problems but spend time in a critical care unit, and patients transferred to our intensive care units from other hospitals. The greatest opportunity to expand the product line comes from increasing the referrals from other hospitals. A methodology was developed to identify the revenue and expenses associated with critical care, based on the analysis of past experience. With this model, we were able to demonstrate a positive contribution margin of dollar 7 million per year related to patients transferred to the institution primarily for critical care services. This can be seen as the profit related to the product line segment of critical care. There was an additional positive contribution margin of dollar 5.8 million attributed to the critical care portion of the hospital stay of

Comprehensive RNA Polymerase II Interactomes Reveal Distinct and Varied Roles for Each Phospho-CTD Residue

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Kevin M. Harlen

2016-06-01

Full Text Available Transcription controls splicing and other gene regulatory processes, yet mechanisms remain obscure due to our fragmented knowledge of the molecular connections between the dynamically phosphorylated RNA polymerase II (Pol II C-terminal domain (CTD and regulatory factors. By systematically isolating phosphorylation states of the CTD heptapeptide repeat (Y1S2P3T4S5P6S7, we identify hundreds of protein factors that are differentially enriched, revealing unappreciated connections between the Pol II CTD and co-transcriptional processes. These data uncover a role for threonine-4 in 3′ end processing through control of the transition between cleavage and termination. Furthermore, serine-5 phosphorylation seeds spliceosomal assembly immediately downstream of 3′ splice sites through a direct interaction with spliceosomal subcomplex U1. Strikingly, threonine-4 phosphorylation also impacts splicing by serving as a mark of co-transcriptional spliceosome release and ensuring efficient post-transcriptional splicing genome-wide. Thus, comprehensive Pol II interactomes identify the complex and functional connections between transcription machinery and other gene regulatory complexes.

Developing critical practice: a South African's perspective.

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Pillay, M

1998-01-01

The manner in which speech and language therapy (SLT) considers communicating evidence of practice with a multicultural clientele is considered in context of cultural imperialism. A conceptual framework (i.e., the curriculum of practice) developed from a South African study (Pillay 1997), is highlighted for use in understanding, evaluating and communicating evidence of practice with the clientele in focus. The lens (or paradigm) used by SLT to view its curriculum of practice may reveal different stories about the same subject. Given this, the critical paradigm is proffered over that of the empirical-analytical (or 'scientific') and hermeneutic-interpretive types of paradigms. Finally, suggestions regarding the development of critical SLT are discussed.

Critical theory and holocaust

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Krstić Predrag

2006-01-01

Full Text Available In this paper the author is attempting to establish the relationship - or the lack of it - of the Critical Theory to the "Jewish question" and justification of perceiving signs of Jewish religious heritage in the thought of the representatives of this movement. The holocaust marked out by the name of "Auschwitz", is here tested as a point where the nature of this relationship has been decided. In this encounter with the cardinal challenge for the contemporary social theory, the particularity of the Frankfurt School reaction is here revealed through Adorno installing Auschwitz as unexpected but lawful emblem of the ending of the course that modern history has assumed. The critique of this "fascination" with Auschwitz, as well as certain theoretical pacification and measured positioning of the holocaust into discontinued plane of "unfinished" and continuation and closure of the valued project, are given through communicative-theoretical pre-orientation of Jürgen Habermas’s Critical Theory and of his followers. Finally, through the work of Detlev Claussen, it is suggested that in the youngest generation of Adorno’s students there are signs of revision to once already revised Critical Theory and a kind of defractured and differentiated return to the initial understanding of the decisiveness of the holocaust experience. This shift in the attitude of the Critical Theory thinkers to the provocation of holocaust is not, however, particularly reflected towards the status of Jews and their tradition, but more to the age old questioning and explanatory patterns for which they served as a "model". The question of validity of the enlightenment project, the nature of occidental rationalism, (nonexistence of historical theology and understanding of the identity and emancipation - describe the circle of problems around which the disagreement is concentrated in the social critical theory.

Influence of Critical Success Factors on Business Development in IT Consulting

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Roman Vasiliev

2015-08-01

Full Text Available This study is intended to explore identification and usage of critical success factors in the activity of IT consulting service providers. Critical success factors and their measures are identified at the industrial level. For the corporate level, the study provides recommendations on elaboration of critical success factors for their further usage. Particular attention is paid to the role of critical success factors in activities of IT consulting service providers involving strategic management, project management, partnership and client relations. This issue has become the subject of the study.

The role of multisensor data fusion in neuromuscular control of a sagittal arm with a pair of muscles using actor-critic reinforcement learning method.

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Golkhou, V; Parnianpour, M; Lucas, C

2004-01-01

In this study, we consider the role of multisensor data fusion in neuromuscular control using an actor-critic reinforcement learning method. The model we use is a single link system actuated by a pair of muscles that are excited with alpha and gamma signals. Various physiological sensor information such as proprioception, spindle sensors, and Golgi tendon organs have been integrated to achieve an oscillatory movement with variable amplitude and frequency, while achieving a stable movement with minimum metabolic cost and coactivation. The system is highly nonlinear in all its physical and physiological attributes. Transmission delays are included in the afferent and efferent neural paths to account for a more accurate representation of the reflex loops. This paper proposes a reinforcement learning method with an Actor-Critic architecture instead of middle and low level of central nervous system (CNS). The Actor in this structure is a two layer feedforward neural network and the Critic is a model of the cerebellum. The Critic is trained by the State-Action-Reward-State-Action (SARSA) method. The Critic will train the Actor by supervisory learning based on previous experiences. The reinforcement signal in SARSA is evaluated based on available alternatives concerning the concept of multisensor data fusion. The effectiveness and the biological plausibility of the present model are demonstrated by several simulations. The system showed excellent tracking capability when we integrated the available sensor information. Addition of a penalty for activation of muscles resulted in much lower muscle coactivation while keeping the movement stable.

Required Critical Conversations Between Medical Examiners/Coroners and Forensic Nurses.

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Infanti Mraz, Megan A

2016-01-01

Forensic teams work with the deceased and their families on a daily basis. The forensic team fulfills an important role during the death process and serves as a medium between the medical community and investigative community. The medical examiner, or coroner, depending on jurisdiction, plays a critical role in the death investigation, whose assessments and findings are a key element in care for the deceased in relation to the investigation. Communication regarding care for the deceased is critical to the completion of the investigation. Nine key discussion points are addressed as a means to launch communications between the forensic team and the medical examiner/coroner's office.

A Conceptual Model for Teaching Critical Thinking in a Knowledge Economy

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Chadwick, Clifton

2011-01-01

Critical thinking, viewed as rational and analytic thinking, is crucial for participation in a knowledge economy and society. This article provides a brief presentation of the importance of teaching critical thinking in a knowledge economy; suggests a conceptual model for teaching thinking; examines research on the historical role of teachers in…

Fight the Dragons: Using Online Discussion to Promote Critical Literacy in Teacher Education

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Woodcock, Christine

2009-01-01

Today's children are bombarded by a range of media, and it is the responsibility of teachers to equip students to engage critically. Just as teachers are responsible to teach critical literacy, teacher educators must help empower teachers to become more critically literate. This paper explores the role of online discussion in the ways it fosters…

Non-equilibrium effects on the two-phase flow critical phenomenon

International Nuclear Information System (INIS)

Sami, S.M.

1988-01-01

In the present study, the choking criterion for nonhomogeneous nonequilibrium two phase flow is obtained by solving the two-fluid model conservation equations. The method of characteristics is employed to predict the critical flow conditions. Critical flow is established after the magnitude of the characteristic slopes (velocities). Critical flow conditions are reached when the smallest characteristic slope becomes equal to zero. Several expression are developed to determine the nonequilibrium mass and heat exchanges in terms of the system dependent parameters derivatives. In addition, comprehensive transition flow regime maps are employed in the calculation of interfacial heat and momentum transfer rates. Numerical results reveal that the proposed model reliably predicts the critical two-phase flow phenomenon under different inlet conditions and compares well with other existing models

Critical Phenomena in Higher Curvature Charged AdS Black Holes

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Arindam Lala

2013-01-01

Full Text Available In this paper, we have studied the critical phenomena in higher curvature charged AdS black holes. We have considered Lovelock-Born-Infeld-AdS black hole as an example. The thermodynamics of the black hole have been studied which reveals the onset of a higher-order phase transition in the black hole in the canonical ensemble (fixed charge ensemble framework. We have analytically derived the critical exponents associated with these thermodynamic quantities. We find that our results fit well with the thermodynamic scaling laws and consistent with the mean field theory approximation. The suggestive values of the other two critical exponents associated with the correlation function and correlation length on the critical surface have been derived.

Activation of acid-sensing ion channels by localized proton transient reveals their role in proton signaling.

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Zeng, Wei-Zheng; Liu, Di-Shi; Liu, Lu; She, Liang; Wu, Long-Jun; Xu, Tian-Le

2015-09-15

Extracellular transients of pH alterations likely mediate signal transduction in the nervous system. Neuronal acid-sensing ion channels (ASICs) act as sensors for extracellular protons, but the mechanism underlying ASIC activation remains largely unknown. Here, we show that, following activation of a light-activated proton pump, Archaerhodopsin-3 (Arch), proton transients induced ASIC currents in both neurons and HEK293T cells co-expressing ASIC1a channels. Using chimera proteins that bridge Arch and ASIC1a by a glycine/serine linker, we found that successful coupling occurred within 15 nm distance. Furthermore, two-cell sniffer patch recording revealed that regulated release of protons through either Arch or voltage-gated proton channel Hv1 activated neighbouring cells expressing ASIC1a channels. Finally, computational modelling predicted the peak proton concentration at the intercellular interface to be at pH 6.7, which is acidic enough to activate ASICs in vivo. Our results highlight the pathophysiological role of proton signalling in the nervous system.

Reiki therapy: a nursing intervention for critical care.

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Toms, Robin

2011-01-01

Complementary and alternative medicine (CAM) is not generally associated with the complexity and intensity of critical care. Most CAM therapies involve slow, calming techniques that seem to be in direct contrast with the fast-paced, highly technical nature of critical care. However, patients in critical care often find themselves coping with the pain and stress of their illness exacerbated by the stress of the critical care environment. Complementary and alternative medicine-related research reveals that complementary therapies, such as Reiki, relieve pain and anxiety and reduce symptoms of stress such as elevated blood pressure and pulse rates. Patients and health care professionals alike have become increasingly interested in complementary and alternative therapies that do not rely on expensive, invasive technology, and are holistic in focus. Reiki is cost-effective, noninvasive, and can easily be incorporated into patient care. The purpose of this article is to examine the science of Reiki therapy and to explore Reiki as a valuable nursing intervention.

Perceived justice and recovery satisfaction: the moderating role of customer-perceived quality

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Jha Subhash

2015-09-01

Full Text Available Recovery strategies are critical to service providers in their efforts to maintain satisfied and loyal customers. While the existing research shows that recovery satisfaction is a function of customer perception of distributive, procedural and interactional justice, the present study considers an important contextual factor - customer-perceived quality of the service provider in the evaluation of justice dimensions and satisfaction. To test the hypotheses proposed, a survey was carried out in the mobile services context. The findings reveal that customer-perceived quality affects the evaluation of justice dimensions and its outcomes. The findings reveal that while distributive justice enhances recovery satisfaction for low perceived quality services, the procedural justice resulted in greater satisfaction in high perceived quality services. Thus, by understanding the role of customer-perceived quality, service managers can deliver effective recovery strategies thereby enhancing satisfaction and loyalty.

Defining and assessing critical thinking skills for student radiographers

International Nuclear Information System (INIS)

Castle, Alan

2009-01-01

Developing critical thinking skills is a key aim of higher education and is important in preparing student radiographers for their future careers in clinical practice. The aim of this paper was to attempt to devise and assess six key components of critical thinking appropriate for radiographic practice. Each of the six components was divided into three dimensions and a Critical Thinking Skills Scoring Chart (CTSSC) devised to assess students' written performance against each dimension. Scores revealed that approximately 30% of students were rated as good and approximately 10% of students were rated as poor in each component, although there was some variability between different dimensions. It is suggested that educators need to encourage and support students to develop their critical thinking skills by reviewing their curriculum to clearly define specific skills and ensure that they are appropriately taught and assessed

Critical current anomaly at the topological quantum phase transition in a Majorana Josephson junction

Energy Technology Data Exchange (ETDEWEB)

Huang, Hong [School of Physics, Sun Yat-sen University, Guangzhou 510275 (China); Liang, Qi-Feng [Department of Physics, Shaoxing University, Shaoxing 312000 (China); Yao, Dao-Xin, E-mail: yaodaox@mail.sysu.edu.cn [School of Physics, Sun Yat-sen University, Guangzhou 510275 (China); Wang, Zhi, E-mail: physicswangzhi@gmail.com [School of Physics, Sun Yat-sen University, Guangzhou 510275 (China)

2017-06-28

Majorana bound states in topological Josephson junctions induce a 4π period current-phase relation. Direct detection of the 4π periodicity is complicated by the quasiparticle poisoning. We reveal that Majorana bound states are also signaled by the anomalous enhancement on the critical current of the junction. We show the landscape of the critical current for a nanowire Josephson junction under a varying Zeeman field, and reveal a sharp step feature at the topological quantum phase transition point, which comes from the anomalous enhancement of the critical current at the topological regime. In multi-band wires, the anomalous enhancement disappears for an even number of bands, where the Majorana bound states fuse into Andreev bound states. This anomalous critical current enhancement directly signals the existence of the Majorana bound states, and also provides a valid signature for the topological quantum phase transition. - Highlights: • We introduce the critical current step as a signal for the topological quantum phase transition. • We study the quantum phase transition in the topological nanowire under a rotating Zeeman field. • We show that the critical current anomaly gradually disappears for systems with more sub-bands.

Learning styles and critical thinking relationship in baccalaureate nursing education: a systematic review.

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Andreou, Christos; Papastavrou, Evridiki; Merkouris, Anastasios

2014-03-01

Critical thinking is a desirable competency for contemporary nurses although there are growing concerns supporting a disturbing paucity in its achievement. Learning styles reflect habitual behaviors which determine distinct preferences within learning situations. Evidence suggests that critical thinking could evolve through learning processes. Variances in critical thinking achievement by nursing students might therefore be influenced by individual learning preferences. The concepts "learning styles" and "critical thinking" have been independently examined in the nursing literature. No reviews were found however exploring their association in nursing education. To identify the potential relationships between learning styles and critical thinking in baccalaureate nursing students. Systematic review. Eleven electronic databases were utilized without geographical and time publishing filters. Hand-searching journals and scanning references from retrieved studies were also performed. Databases were searched for descriptive correlational studies which considered the relationship between learning styles and critical thinking in baccalaureate nursing students. The authors independently progressed three stage screening. Retrieved articles were reviewed at title, abstract and full text levels according to predetermined criteria. All included studies were quality appraised using a rating tool for descriptive studies. Six studies were finally included. Findings were grouped under four key themes: predominant learning styles, critical thinking scoring, critical thinking evolution across academic progress and learning styles-critical thinking correlations. Learning styles' diversities, weak critical thinking and inconsistent evolution through academic progress were revealed across studies. Critical thinking differed significantly between learning styles. Commonly accepted models in nursing education were lacking in both learning styles and critical thinking. Within studies

Critical roles for LIGHT and its receptors in generating T cell-mediated immunity during Leishmania donovani infection.

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Amanda C Stanley

2011-10-01

Full Text Available LIGHT (TNFSF14 is a member of the TNF superfamily involved in inflammation and defence against infection. LIGHT signals via two cell-bound receptors; herpes virus entry mediator (HVEM and lymphotoxin-beta receptor (LTβR. We found that LIGHT is critical for control of hepatic parasite growth in mice with visceral leishmaniasis (VL caused by infection with the protozoan parasite Leishmania donovani. LIGHT-HVEM signalling is essential for early dendritic cell IL-12/IL-23p40 production, and the generation of IFNγ- and TNF-producing T cells that control hepatic infection. However, we also discovered that LIGHT-LTβR interactions suppress anti-parasitic immunity in the liver in the first 7 days of infection by mechanisms that restrict both CD4(+ T cell function and TNF-dependent microbicidal mechanisms. Thus, we have identified distinct roles for LIGHT in infection, and show that manipulation of interactions between LIGHT and its receptors may be used for therapeutic advantage.

Effects of stressor characteristics on early warning signs of critical transitions and "critical coupling" in complex dynamical systems.

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Blume, Steffen O P; Sansavini, Giovanni

2017-12-01

Complex dynamical systems face abrupt transitions into unstable and catastrophic regimes. These critical transitions are triggered by gradual modifications in stressors, which push the dynamical system towards unstable regimes. Bifurcation analysis can characterize such critical thresholds, beyond which systems become unstable. Moreover, the stochasticity of the external stressors causes small-scale fluctuations in the system response. In some systems, the decomposition of these signal fluctuations into precursor signals can reveal early warning signs prior to the critical transition. Here, we present a dynamical analysis of a power system subjected to an increasing load level and small-scale stochastic load perturbations. We show that the auto- and cross-correlations of bus voltage magnitudes increase, leading up to a Hopf bifurcation point, and further grow until the system collapses. This evidences a gradual transition into a state of "critical coupling," which is complementary to the established concept of "critical slowing down." Furthermore, we analyze the effects of the type of load perturbation and load characteristics on early warning signs and find that gradient changes in the autocorrelation provide early warning signs of the imminent critical transition under white-noise but not for auto-correlated load perturbations. Furthermore, the cross-correlation between all voltage magnitude pairs generally increases prior to and beyond the Hopf bifurcation point, indicating "critical coupling," but cannot provide early warning indications. Finally, we show that the established early warning indicators are oblivious to limit-induced bifurcations and, in the case of the power system model considered here, only react to an approaching Hopf bifurcation.

Alpha-CaMKII plays a critical role in determining the aggressive behavior of human osteosarcoma.

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Daft, Paul G; Yuan, Kaiyu; Warram, Jason M; Klein, Michael J; Siegal, Gene P; Zayzafoon, Majd

2013-04-01

Osteosarcoma is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in osteosarcoma treatment, more specific molecular targets are needed as potential therapeutic options. One target of interest is α-Ca(2+)/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca(2+)-linked signaling, which has been shown to regulate tumor cell proliferation and differentiation. Here, we investigate the role of α-CaMKII in the growth and tumorigenicity of human osteosarcoma. We show that α-CaMKII is highly expressed in primary osteosarcoma tissue derived from 114 patients, and is expressed in varying levels in different human osteosarcoma (OS) cell lines [MG-63, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)/HOS, and 143B). To examine whether α-CaMKII regulates osteosarcoma tumorigenic properties, we genetically inhibited α-CaMKII in two osteosarcoma cell lines using two different α-CaMKII shRNAs delivered by lentiviral vectors and overexpressed α-CaMKII by retrovirus. The genetic deletion of α-CaMKII by short hairpin RNA (shRNA) in MG-63 and 143B cells resulted in decreased proliferation (50% and 41%), migration (22% and 25%), and invasion (95% and 90%), respectively. The overexpression of α-CaMKII in HOS cells resulted in increased proliferation (240%), migration (640%), and invasion (10,000%). Furthermore, α-CaMKII deletion in MG-63 cells significantly reduced tumor burden in vivo (65%), whereas α-CaMKII overexpression resulted in tumor formation in a previously nontumor forming osteosarcoma cell line (HOS). Our results suggest that α-CaMKII plays a critical role in determining the aggressive phenotype of osteosarcoma, and its inhibition could be an attractive therapeutic target to combat this devastating adolescent disease. ©2013 AACR.

Preventing and managing exacerbations in COPD – critical appraisal of the role of tiotropium

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Donald P Tashkin

2010-02-01

Full Text Available Donald P TashkinDepartment of Medicine, Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA,Los Angeles, CA, USAAbstract: The course of COPD is punctuated by acute exacerbations that are associated with an increase in the morbidity and mortality related to this chronic disease and may contribute to its rate of progression. Therefore, preventing and treating exacerbations are major goals of COPD management. The role of tiotropium in the prevention of exacerbations has been investigated in several placebo-controlled randomized clinical trials varying in duration from 3 months to 4 years in patients with moderate to very severe COPD. In all of these trials, tiotropium has uniformly reduced the proportion of patients experiencing at least one exacerbation and delayed the time to the first exacerbation compared with placebo. In the longer trials (≥6 months’ duration tiotropium has also reduced the exposure-adjusted incidence rate of exacerbations. In trials of at least 1 year in duration, tiotropium either significantly reduced the risk of hospitalization for an exacerbation and/or the proportion of patients with an exacerbation-related hospitalization. In a meta-analysis that included 15 trials of tiotropium vs either placebo (n = 13 and/or a longacting beta-agonist (LABA; n = 4, tiotropium significantly reduced the odds of experiencing an exacerbation compared to placebo as well as a LABA. The potential additive benefits of tiotropium to those of a LABA and/or inhaled corticosteroid in reducing exacerbations require further investigation. The mechanism whereby tiotropium reduces exacerbations is not due to an anti-inflammatory effect but more likely relates to its property of causing a sustained increase in airway patency and reduction in hyperinflation, thereby counteracting the tendency for respiratory insults to worsen airflow obstruction and hyperinflation. For the management of acute exacerbations, an

Critical Mathematics education: Past, present and future

DEFF Research Database (Denmark)

contribution to the shaping of those concerns in the international community of mathematics educators and mathematics education researchers. This book gathers contributions of researchers from five continents, for whom critical mathematics education has been an inspiration to think about many different topics...... such as the dialogical and political dimensions of teacher education, mathematical modeling, the philosophy of mathematics from social and political perspectives, teaching practices in classrooms, the connection between mathematics and society, the scope and limits of critical thinking in relation to mathematics......Critical mathematics education brings together a series of concerns related to mathematics and its role in society, the practices of teaching and learning of mathematics in educational settings, and the practices of researching mathematics education. The work of Ole Skovsmose has provided a seminal...

The Relationship between Values and Critical Thinking Dispositions of Pre-Service Teachers

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Mustafa Volkan Coskun

2016-12-01

Full Text Available This study aimed to reveal the relationship between personality values and critical thinking disposition of pre-service teachers studying in a Faculty of Education. The study was designed using the survey model. The population of this study consisted of pre-service teachers studying at the Faculty of Education at Mugla Sitki Kocman University, Turkey, during the 2015-2016 academic year. The sample of the study consisted of 570 pre-service teachers who were selected by using disproportionate cluster sampling technique. The data of the study were obtained through the administration of the Florida Critical Disposition Scale (UF/EMI and University Students Values Scale (USVS. USVS was developed within the scope of the present study. Descriptive statistics, t-test, ANOVA, and multivariate regression analysis were used to analyze the data. The study revealed that the pre-service teachers attributed highest value to sensitivity. These values were identified to be followed with respect to diversity, trustability, and responsibility. In addition, the level of students’ critical thinking dispositions was found to be at the average level. Furthermore, the values of students explained approximately one-third of the critical-thinking dispositions. The values of sensitivity, responsibility and respect for diversity were determined to be the significant predictors of students’ critical-thinking dispositions.

The role of transition metal transporters for iron, zinc, manganese, and copper in the pathogenesis of Yersinia pestis.

Science.gov (United States)

Perry, Robert D; Bobrov, Alexander G; Fetherston, Jacqueline D

2015-06-01

Yersinia pestis, the causative agent of bubonic, septicemic and pneumonic plague, encodes a multitude of Fe transport systems. Some of these are defective due to frameshift or IS element insertions, while others are functional in vitro but have no established role in causing infections. Indeed only 3 Fe transporters (Ybt, Yfe and Feo) have been shown to be important in at least one form of plague. The yersiniabactin (Ybt) system is essential in the early dermal/lymphatic stages of bubonic plague, irrelevant in the septicemic stage, and critical in pneumonic plague. Two Mn transporters have been characterized (Yfe and MntH). These two systems play a role in bubonic plague but the double yfe mntH mutant is fully virulent in a mouse model of pneumonic plague. The same in vivo phenotype occurs with a mutant lacking two (Yfe and Feo) of four ferrous transporters. A role for the Ybt siderophore in Zn acquisition has been revealed. Ybt-dependent Zn acquisition uses a transport system completely independent of the Fe-Ybt uptake system. Together Ybt components and ZnuABC play a critical role in Zn acquisition in vivo. Single mutants in either system retain high virulence in a mouse model of septicemic plague while the double mutant is completely avirulent.

STAT2 Knockout Syrian Hamsters Support Enhanced Replication and Pathogenicity of Human Adenovirus, Revealing an Important Role of Type I Interferon Response in Viral Control.

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Karoly Toth

2015-08-01

Full Text Available Human adenoviruses have been studied extensively in cell culture and have been a model for studies in molecular, cellular, and medical biology. However, much less is known about adenovirus replication and pathogenesis in vivo in a permissive host because of the lack of an adequate animal model. Presently, the most frequently used permissive immunocompetent animal model for human adenovirus infection is the Syrian hamster. Species C human adenoviruses replicate in these animals and cause pathology that is similar to that seen with humans. Here, we report findings with a new Syrian hamster strain in which the STAT2 gene was functionally knocked out by site-specific gene targeting. Adenovirus-infected STAT2 knockout hamsters demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs of STAT2 knockout animals was 100- to 1000-fold higher than that in wild-type hamsters. Notably, the adaptive immune response to adenovirus is not adversely affected in STAT2 knockout hamsters, and surviving hamsters cleared the infection by 7 to 10 days post challenge. We show that the Type I interferon pathway is disrupted in these hamsters, revealing the critical role of interferon-stimulated genes in controlling adenovirus infection. This is the first study to report findings with a genetically modified Syrian hamster infected with a virus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting human adenovirus replication in a permissive animal model. Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model: STAT2 knockout Syrian hamster may also be an important animal model for studying other viral infections, including Ebola-, hanta-, and dengue viruses, where Type I interferon-mediated innate immunity prevents wild type hamsters from being effectively infected to be used as

A critical Social Work project

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Carlos Montaño

2006-04-01

Full Text Available Contemporary social transformations, operated by the neoliberal program under the command of financial capital, bring new challenges to the group of citizens and men and women who live by the sale of their labor power. Social workers, individually and collectively, are not separate from this reality. The profession was characterized by its confrontation with these challenges and its questioning and analysis of its role in society, in its attempt to assume more critical profiles and commitments to the interests of workers and the subaltern sectors. An example of this is the “Reconceptualization Movement” and the later attempt to define na “Alternative Social Service” concerned with the meaning of its practice, with the process of critical knowledge, with a criticism of capitalism and its situations of social injustice. The current challenges include overcoming earlier weaknesses, collectively constructing an ethicalpolitical professional project that can competently and committedly confront, at the heart of progressive social forces, the conditions in which workers live (with or without employment as well as other subaltern populations.

Characteristic of critical and creative thinking of students of mathematics education study program

Science.gov (United States)

Rochmad; Agoestanto, A.; Kharis, M.

2018-03-01

Critical and creative thinking give important role in learning matematics for mathematics education students. This research to explored the characteristic of critical and creative thinking of students of mathematics study program in mathematics department. Critical thinking and creative thinking can be illustrated as two sides of a coin, which one is associated to the other. In elementary linear algebra courses, however, critical thinking can be seen as a foundation to build students’ creative thinking.

Characterization of neutron leakage probability, k /SUB eff/ , and critical core surface mass density of small reactor assemblies through the Trombay criticality formula

International Nuclear Information System (INIS)

Kumar, A.; Rao, K.S.; Srinivasan, M.

1983-01-01

The Trombay criticality formula (TCF) has been derived by incorporating a number of well-known concepts of criticality physics to enable prediction of changes in critical size or k /SUB eff/ following alterations in geometrical and physical parameters of uniformly reflected small reactor assemblies characterized by large neutron leakage from the core. The variant parameters considered are size, shape, density and diluent concentration of the core, and density and thickness of the reflector. The effect of these changes (except core size) manifests, through sigma /SUB c/ the critical surface mass density of the ''corresponding critical core,'' that sigma, the massto-surface-area ratio of the core,'' is essentially a measure of the product /rho/ extended to nonspherical systems and plays a dominant role in the TCF. The functional dependence of k /SUB eff/ on sigma/sigma /SUB c/ , the system size relative to critical, is expressed in the TCF through two alternative representations, namely the modified Wigner rational form and, an exponential form, which is given

Critical role of SAP in progression and reactivation but not maintenance of T cell-dependent humoral immunity.

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Zhong, Ming-Chao; Veillette, André

2013-03-01

Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is a small adaptor molecule mutated in X-linked lymphoproliferative disease, a human immunodeficiency. SAP plays a critical role in the initiation of T cell-dependent B cell responses leading to germinal center reaction, the production of high-affinity antibodies, and B cell memory. However, whether SAP has a role in these responses beyond their initiation is not known. It is important to address this matter not only for mechanistic reasons but also because blockade of the SAP pathway is being contemplated as a means to treat autoimmune diseases in humans. Using an inducibly SAP deficient mouse, we found that SAP was required not only for the initiation but also for the progression of primary T cell-driven B cell responses to haptens. It was also necessary for the reactivation of T cell-dependent B cell immunity during secondary immune responses. These activities consistently correlated with the requirement of SAP for full expression of the lineage commitment factor Bcl-6 in follicular T helper (T(FH)) cells. However, once memory B cells and long-lived antibody-secreting cells were established, SAP became dispensable for maintaining T cell-dependent B cell responses. Thus, SAP is pivotal for nearly all phases, but not for maintenance, of T cell-driven B cell humoral immunity. These findings may have implications for the treatment of immune disorders by targeting the SAP pathway.

New Type of Quantum Criticality in the Pyrochlore Iridates

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Lucile Savary

2014-11-01

Full Text Available Magnetic fluctuations and electrons couple in intriguing ways in the vicinity of zero-temperature phase transitions—quantum critical points—in conducting materials. Quantum criticality is implicated in non-Fermi liquid behavior of diverse materials and in the formation of unconventional superconductors. Here, we uncover an entirely new type of quantum critical point describing the onset of antiferromagnetism in a nodal semimetal engendered by the combination of strong spin-orbit coupling and electron correlations, and which is predicted to occur in the iridium oxide pyrochlores. We formulate and solve a field theory for this quantum critical point by renormalization group techniques and show that electrons and antiferromagnetic fluctuations are strongly coupled and that both these excitations are modified in an essential way. This quantum critical point has many novel features, including strong emergent spatial anisotropy, a vital role for Coulomb interactions, and highly unconventional critical exponents. Our theory motivates and informs experiments on pyrochlore iridates and constitutes a singular realistic example of a nontrivial quantum critical point with gapless fermions in three dimensions.

β-Catenin is critical for cerebellar foliation and lamination.

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Jing Wen

Full Text Available The cerebellum has a conserved foliation pattern and a well-organized layered structure. The process of foliation and lamination begins around birth. β-catenin is a downstream molecule of Wnt signaling pathway, which plays a critical role in tissue organization. Lack of β-catenin at early embryonic stages leads to either prenatal or neonatal death, therefore it has been difficult to resolve its role in cerebellar foliation and lamination. Here we used GFAP-Cre to ablate β-catenin in neuronal cells of the cerebellum after embryonic day 12.5, and found an unexpected role of β-catenin in determination of the foliation pattern. In the mutant mice, the positions of fissure formation were changed, and the meninges were improperly incorporated into fissures. At later stages, some lobules were formed by Purkinje cells remaining in deep regions of the cerebellum and the laminar structure was dramatically altered. Our results suggest that β-catenin is critical for cerebellar foliation and lamination. We also found a non cell-autonomous role of β-catenin in some developmental properties of major cerebellar cell types during specific stages.

Statistical analysis of the distribution of critical current and the correlation of n value to the critical current of bent Bi2223 composite tape

International Nuclear Information System (INIS)

Ochiai, S; Matsubayashi, H; Okuda, H; Osamura, K; Otto, A; Malozemoff, A

2009-01-01

Distributions of local and overall critical currents and correlation of n value to the critical current of bent Bi2223 composite tape were studied from the statistical viewpoint. The data of the local and overall transport critical currents and n values of the Bi2223 composite tape specimens were collected experimentally for a wide range of bending strain (0-1.1%) by using the specimens, designed so as to characterize the local and overall critical currents and n values. The measured local and overall critical currents were analyzed with various types of Weibull distribution function. Which of the Weibull distribution functions is suitable for the description of the distribution of local and overall critical currents at each bending strain, and also how much the Weibull parameter values characterizing the distribution vary with bending strain, were revealed. Then we attempted to reproduce the overall critical current distribution and correlation of the overall n value to the overall critical current from the distribution of local critical currents and the correlation of the local n value to the local critical current by a Monte Carlo simulation. The measured average values of critical current and n value at each bending strain and the correlation of n value to critical current were reproduced well by the present simulation, while the distribution of critical current values was reproduced fairly well but not fully. The reason for this is discussed.

Impact of resonance decays on critical point signals in net-proton fluctuations

Energy Technology Data Exchange (ETDEWEB)

Bluhm, Marcus; Schaefer, Thomas [North Carolina State University, Department of Physics, Raleigh, NC (United States); Nahrgang, Marlene [SUBATECH, UMR 6457, Universite de Nantes, Ecole des Mines de Nantes, IN2P3/CNRS, Nantes (France); Duke University, Department of Physics, Durham, NC (United States); Bass, Steffen A. [Duke University, Department of Physics, Durham, NC (United States)

2017-04-15

The non-monotonic beam energy dependence of the higher cumulants of net-proton fluctuations is a widely studied signature of the conjectured presence of a critical point in the QCD phase diagram. In this work we study the effect of resonance decays on critical fluctuations. We show that resonance effects reduce the signatures of critical fluctuations, but that for reasonable parameter choices critical effects in the net-proton cumulants survive. The relative role of resonance decays has a weak dependence on the order of the cumulants studied with a slightly stronger suppression of critical effects for higher-order cumulants. (orig.)

The Role of Gender in Workplace Stress: A Critical Literature Review

Science.gov (United States)

Gyllensten, Kristina; Palmer, Stephen

2005-01-01

Objective: The aim of this review was to evaluate research relating to the role of gender in the level of workplace stress. A further aim was to review literature relating to stressors of particular relevance to working women. These stressors included, multiple roles, lack of career progress and discrimination and stereotyping. Design: Systematic…

Anesthetics rapidly promote synaptogenesis during a critical period of brain development.

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Mathias De Roo

Full Text Available Experience-driven activity plays an essential role in the development of brain circuitry during critical periods of early postnatal life, a process that depends upon a dynamic balance between excitatory and inhibitory signals. Since general anesthetics are powerful pharmacological modulators of neuronal activity, an important question is whether and how these drugs can affect the development of synaptic networks. To address this issue, we examined here the impact of anesthetics on synapse growth and dynamics. We show that exposure of young rodents to anesthetics that either enhance GABAergic inhibition or block NMDA receptors rapidly induce a significant increase in dendritic spine density in the somatosensory cortex and hippocampus. This effect is developmentally regulated; it is transient but lasts for several days and is also reproduced by selective antagonists of excitatory receptors. Analyses of spine dynamics in hippocampal slice cultures reveals that this effect is mediated through an increased rate of protrusions formation, a better stabilization of newly formed spines, and leads to the formation of functional synapses. Altogether, these findings point to anesthesia as an important modulator of spine dynamics in the developing brain and suggest the existence of a homeostatic process regulating spine formation as a function of neural activity. Importantly, they also raise concern about the potential impact of these drugs on human practice, when applied during critical periods of development in infants.

Platonic Dialogue, Maieutic Method and Critical Thinking

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Leigh, Fiona

2007-01-01

In this paper I offer a reading of one of Plato's later works, the "Sophist", that reveals it to be informed by principles comparable on the face of it with those that have emerged recently in the field of critical thinking. As a development of the famous Socratic method of his teacher, I argue, Plato deployed his own pedagogical method, a…

Disordered eating and suicidal intent: the role of thin ideal internalisation, shame and family criticism.

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Unikel, C; Von Holle, A; Bulik, C M; Ocampo, R

2012-01-01

We explored the effect of thin ideal internalisation, shame proneness and family criticism on disordered eating and suicidal intent in female Mexican adolescents. We studied a probabilistic sample of 2537 high school students in central Mexico, stratified by marginalisation status and migratory intensity. We used a generalised logistic regression model to estimate the odds of disordered eating and suicidal intent across scores for three predictors: Internalisation of the thin ideal, shame and family criticism. Disordered eating was reported by 4.2% (95% CI = 0.9-7.5%) and suicidal intent by 13.2% (95% CI = 12.0-14.4%) of girls. The unadjusted odds ratios of any disordered eating for thin ideal internalisation, shame proneness and familial criticism were 1.2, 1.1 and 3.2, respectively. The positive association between thin ideal internalisation and disordered eating remained even after controlling for shame proneness and familial criticism. The association of these variables with suicidal intent was weaker. Results support stronger effects for disordered eating than suicidal intent across the three unadjusted predictors. It also highlights the presence of the relationship of criticism and disordered eating in female adolescents from low and middle socio-economic backgrounds. Copyright © 2010 John Wiley & Sons, Ltd. and Eating Disorders Association.

Do critical care units play a role in the management of gynaecological oncology patients? The contribution of gynaecologic oncologist in running critical care units.

Science.gov (United States)

Davidovic-Grigoraki, Miona; Thomakos, Nikolaos; Haidopoulos, Dimitrios; Vlahos, Giorgos; Rodolakis, Alexandros

2017-03-01

Routine post-operative care in high dependency unit (HDU), surgical intensive care unit (SICU) and intensive care unit (ICU) after high-risk gynaecological oncology surgical procedures may allow for greater recognition and correct management of post-operative complications, thereby reducing long-term morbidity and mortality. On the other hand, unnecessary admissions to these units lead to increased morbidity - nosocomial infections, increased length of hospital stay and higher hospital costs. Gynaecological oncology surgeons continue to look after their patient in the HDU/SICU and have the final role in decision-making on day-to-day basis, making it important to be well versed in critical care management and ensure the best care for their patients. Post-operative monitoring and the presence of comorbid illnesses are the most common reasons for admission to the HDU/SICU. Elderly and malnutritioned patients, as well as, bowel resection, blood loss or greater fluid resuscitation during the surgery have prolonged HDU/SICU stay. Patients with ovarian cancer have a worse survival outcome than the patients with other types of gynaecological cancer. Dependency care is a part of surgical management and it should be incorporated formally into gynaecologic oncology training programme. © 2016 John Wiley & Sons Ltd.

Mobile computing in critical care.

Science.gov (United States)

Lapinsky, Stephen E

2007-03-01

Handheld computing devices are increasingly used by health care workers, and offer a mobile platform for point-of-care information access. Improved technology, with larger memory capacity, higher screen resolution, faster processors, and wireless connectivity has broadened the potential roles for these devices in critical care. In addition to the personal information management functions, handheld computers have been used to access reference information, management guidelines and pharmacopoeias as well as to track the educational experience of trainees. They can act as an interface with a clinical information system, providing rapid access to patient information. Despite their popularity, these devices have limitations related to their small size, and acceptance by physicians has not been uniform. In the critical care environment, the risk of transmitting microorganisms by such a portable device should always be considered.

The Critical Role of Potassium in Plant Stress Response

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Min Wang

2013-04-01

Full Text Available Agricultural production continues to be constrained by a number of biotic and abiotic factors that can reduce crop yield quantity and quality. Potassium (K is an essential nutrient that affects most of the biochemical and physiological processes that influence plant growth and metabolism. It also contributes to the survival of plants exposed to various biotic and abiotic stresses. The following review focuses on the emerging role of K in defending against a number of biotic and abiotic stresses, including diseases, pests, drought, salinity, cold and frost and waterlogging. The availability of K and its effects on plant growth, anatomy, morphology and plant metabolism are discussed. The physiological and molecular mechanisms of K function in plant stress resistance are reviewed. This article also evaluates the potential for improving plant stress resistance by modifying K fertilizer inputs and highlights the future needs for research about the role of K in agriculture.

Role of experimental resolution in measurements of critical layer thickness for strained-layer epitaxy

International Nuclear Information System (INIS)

Fritz, I.J.

1987-01-01

Experimental measurements of critical layer thicknesses (CLT's) in strained-layer epitaxy are considered. Finite experimental resolution can have a major effect on measured CLT's and can easily lead to spurious results. The theoretical approach to critical layer thicknesses of J. W. Matthews [J. Vac. Sci. Technol. 12, 126 (1975)] has been modified in a straightforward way to predict the apparent critical thickness for an experiment with finite resolution in lattice parameter. The theory has also been modified to account for the general empirical result that fewer misfit dislocations are generated than predicted by equilibrium calculation. The resulting expression is fit to recent x-ray diffraction data on InGaAs/GaAs and SiGe/Si. The results suggest that CLT's in these systems may not be significantly larger than predicted by equilibrium theory, in agreement with high-resolution measurements

Music critic Gustav Michel

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Vasić Aleksandar N.

2004-01-01

oppose the National Theatre administrations when they decided to add operettas to its repertoire. Here he also differs from expert critics, for example Miloje Milojević or Petar Krstić - who led a real crusade against operetta. Michel paid scrupulous attention to correct diction, as an important part of the vocal technique. As a critic, Gustav Michel was inclined to relatively modern music. He was not strict in his judgments of Serbian performers’ and composers’ achievements; he always took account of very difficult conditions under which the Serbian people, after many centuries of the Turkish occupation, started its cultural and musical emancipation in the 19th century. (He was especially considerate towards novice musicians However his critical assessment of the genre status of the overture to the first Serbian opera, "Na uranku" ("At Dawn" by Stanislav Binički, revealed an incisive critic. The weak side of his critic lies in too general language not exact enough for characteristics of musical interpretations. However Gustav Michel was a witty and ironic writer, and his few articles marked the beginning of an expert and modern music critic in Serbia.

Analysis of core-periphery organization in protein contact networks reveals groups of structurally and functionally critical residues.

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Isaac, Arnold Emerson; Sinha, Sitabhra

2015-10-01

The representation of proteins as networks of interacting amino acids, referred to as protein contact networks (PCN), and their subsequent analyses using graph theoretic tools, can provide novel insights into the key functional roles of specific groups of residues. We have characterized the networks corresponding to the native states of 66 proteins (belonging to different families) in terms of their core-periphery organization. The resulting hierarchical classification of the amino acid constituents of a protein arranges the residues into successive layers - having higher core order - with increasing connection density, ranging from a sparsely linked periphery to a densely intra-connected core (distinct from the earlier concept of protein core defined in terms of the three-dimensional geometry of the native state, which has least solvent accessibility). Our results show that residues in the inner cores are more conserved than those at the periphery. Underlining the functional importance of the network core, we see that the receptor sites for known ligand molecules of most proteins occur in the innermost core. Furthermore, the association of residues with structural pockets and cavities in binding or active sites increases with the core order. From mutation sensitivity analysis, we show that the probability of deleterious or intolerant mutations also increases with the core order. We also show that stabilization centre residues are in the innermost cores, suggesting that the network core is critically important in maintaining the structural stability of the protein. A publicly available Web resource for performing core-periphery analysis of any protein whose native state is known has been made available by us at http://www.imsc.res.in/ ~sitabhra/proteinKcore/index.html.

Rethinking Critical Voice: Materiality and Situated Knowledges.

Science.gov (United States)

Wood, Julia T.; Cox, Robert

1993-01-01

Responds to several essays in the same journal issue. Suggests distinct yet equally important roles of theory and lived experience, concepts, and materiality in speech communication research. Argues for an engaged scholarly attitude that views the self as relational, others' accounts as valid, research as self-critical, and judgment as a…

EMPOWERING NON-NATIVE ENGLISH SPEAKING TEACHERS THROUGH CRITICAL PEDAGOGY

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Nur Hayati

2010-02-01

Full Text Available Critical pedagogy is a teaching approach that aims to develop students’ critical thinking, political and social awareness, and self esteem through dialogue learning and reflection. Related to the teaching of EFL, this pedagogy holds the potential to empower non native English speaking teachers (NNESTs when incorporated into English teacher education programs. It can help aspiring NNESTs to grow awareness of the political and sociocultural implications of EFL teaching, to foster their critical thinking on any concepts or ideas regarding their profession, and more importantly, to recognize their strengths as NNESTs. Despite the potential, the role of critical pedagogy in improving EFL teacher education program in Indonesia has not been sufficiently discussed. This article attempts to contribute to the discussion by looking at a number of ways critical pedagogy can be incorporated in the programs, the rationale for doing so, and the challenges that might come on the way.

Critical and strategic materials proceedings of the laboratory study group meeting

International Nuclear Information System (INIS)

1983-06-01

These Proceedings serve to identify the appropriate role for the DOE-BES-DMS Laboratory program concerning critical and strategic materials, identify and articulate high priority DOE-BES-DMS target areas so as to maximize programmatic responsiveness to national needs concerning critical and strategic materials, and identify research, expertise, and resources (including Collaborative Research Centers) that are relevant to critical and strategic materials that is either underway or in place under the DOE-BES-DMS Laboratory program. Laboratory statements of collaborative research are given

Determination of critical breakage conditions for double glazing in fire

International Nuclear Information System (INIS)

Wang, Yu; Li, Ke; Su, Yanfei; Lu, Wei; Wang, Qingsong; Sun, Jinhua; He, Linghui; Liew, K.M.

2017-01-01

Highlights: • Critical heat fluxes of exposed and ambient panes are 6 kW/m"2 and 25 kW/m"2. • Critical temperature difference of fire side pane is around 60 °C. • The ambient pane survives three times longer due to radiation filter and air gap. • Heat transfer in double glazing is revealed by a heat flux based theoretical model. - Abstract: Double glazing unit normally demonstrates better fire resistance than single glazing, but the knowledge on its thermal behavior and heat transfer mechanism during fire is limited. In this work, nine double glazing units were heated by a 500 × 500 mm"2 pool fire. The incident heat flux, temperature on four surfaces, breakage time and cracking behavior were obtained. The critical breakage conditions for interior and exterior panes were determined through gradually decreasing the glass-burner distance from 750 mm to 450 mm. It is established that in double glazing the pane at ambient side can withstand significantly more time than the pane exposed to fire. The critical temperature difference for interior pane is 60 °C; the critical temperature of exterior pane breakage is much higher due to no frame-covered area. In addition, the heat flux at the time of crack initiation is 6 kW/m"2 for the pane at fire side, while more than 25 kW/m"2 for ambient side pane. To reveal the heat transfer mechanism in glazing-air-glazing, theoretical and numerical investigations are also performed, which agrees well with the experimental results.

A conceptual framework for developing a critical thinking self-assessment scale.

Science.gov (United States)

Nair, Girija G; Stamler, Lynnette Leeseberg

2013-03-01

Nurses must be talented critical thinkers to cope with the challenges related to the ever-changing health care system, population trends, and extended role expectations. Several countries now recognize critical thinking skills (CTS) as an expected outcome of nursing education programs. Critical thinking has been defined in multiple ways by philosophers, critical thinking experts, and educators. Nursing experts conceptualize critical thinking as a process involving cognitive and affective domains of reasoning. Nurse educators are often challenged with teaching and measuring CTS because of their latent nature and the lack of a uniform definition of the concept. In this review of the critical thinking literature, we examine various definitions, identify a set of constructs that define critical thinking, and suggest a conceptual framework on which to base a self-assessment scale for measuring CTS. Copyright 2013, SLACK Incorporated.

Education within Sustainable Development: Critical Thinking Formation on ESL Class

Science.gov (United States)

Pevneva, Inna; Gavrishina, Olga; Smirnova, Anna; Rozhneva, Elena; Yakimova, Nataliya

2017-11-01

The article is devoted to consideration of the critical thinking formation in course of foreign language teaching within the education for sustainable development as a crucial skill of perspective employee and a future leader of Russian employment market. The necessity to include the component of problem education and critical thinking methodology in course of the foreign language class is justified along with analysis of the basic principles of critical thinking and certain strategies that can be implied in class. This model targets communicative language competences of students as well as critical thinking due to interconnection of various types of cognitive activities in class. The role in personality development of the students is considered along with the formation and enhancing of critical thinking skills within the modern personality-oriented approach.

The role of backward associative strength in false recognition of DRM lists with multiple critical words.

Science.gov (United States)

Beato, María S; Arndt, Jason

2017-08-01

Memory is a reconstruction of the past and is prone to errors. One of the most widely-used paradigms to examine false memory is the Deese/Roediger-McDermott (DRM) paradigm. In this paradigm, participants studied words associatively related to a non-presented critical word. In a subsequent memory test critical words are often falsely recalled and/or recognized. In the present study, we examined the influence of backward associative strength (BAS) on false recognition using DRM lists with multiple critical words. In forty-eight English DRM lists, we manipulated BAS while controlling forward associative strength (FAS). Lists included four words (e.g., prison, convict, suspect, fugitive) simultaneously associated with two critical words (e.g., CRIMINAL, JAIL). The results indicated that true recognition was similar in high-BAS and low-BAS lists, while false recognition was greater in high-BAS lists than in low-BAS lists. Furthermore, there was a positive correlation between false recognition and the probability of a resonant connection between the studied words and their associates. These findings suggest that BAS and resonant connections influence false recognition, and extend prior research using DRM lists associated with a single critical word to studies of DRM lists associated with multiple critical words.

How Critical Is Critical Thinking?

Science.gov (United States)

Shaw, Ryan D.

2014-01-01

Recent educational discourse is full of references to the value of critical thinking as a 21st-century skill. In music education, critical thinking has been discussed in relation to problem solving and music listening, and some researchers suggest that training in critical thinking can improve students' responses to music. But what exactly is…

The critical role of ocean container transport in global supply chain performance

NARCIS (Netherlands)

Fransoo, J.C.; Lee, C.Y.

2013-01-01

With supply chains distributed across global markets, ocean container transport now is a critical element of any such supply chain. We identify key characteristics of ocean container transport from a supply chain perspective. We find that unlike continental (road) transport, service offerings tend

Development and psychometric testing of the Carter Assessment of Critical Thinking in Midwifery (Preceptor/Mentor version).

Science.gov (United States)

Carter, Amanda G; Creedy, Debra K; Sidebotham, Mary

2016-03-01

develop and test a tool designed for use by preceptors/mentors to assess undergraduate midwifery students׳ critical thinking in practice. a descriptive cohort design was used. participants worked in a range of maternity settings in Queensland, Australia. 106 midwifery clinicians who had acted in the role of preceptor for undergraduate midwifery students. this study followed a staged model for tool development recommended by DeVellis (2012). This included generation of items, content validity testing through mapping of draft items to critical thinking concepts and expert review, administration of items to a convenience sample of preceptors, and psychometric testing. A 24 item tool titled the XXXX Assessment of Critical Thinking in Midwifery (CACTiM) was completed by registered midwives in relation to students they had recently preceptored in the clinical environment. ratings by experts revealed a content validity index score of 0.97, representing good content validity. An evaluation of construct validity through factor analysis generated three factors: 'partnership in practice', 'reflection on practice' and 'practice improvements'. The scale demonstrated good internal reliability with a Cronbach alpha coefficient of 0.97. The mean total score for the CACTiM scale was 116.77 (SD=16.68) with a range of 60-144. Total and subscale scores correlated significantly. the CACTiM (Preceptor/Mentor version) was found to be a valid and reliable tool for use by preceptors to assess critical thinking in undergraduate midwifery students. given the importance of critical thinking skills for midwifery practice, mapping and assessing critical thinking development in students׳ practice across an undergraduate programme is vital. The CACTiM (Preceptor/Mentor version) has utility for clinical education, research and practice. The tool can inform and guide preceptors׳ assessment of students׳ critical thinking in practice. The availability of a reliable and valid tool can be used to

Reappraisal of criticality for two-layer flows and its role in the generation of internal solitary waves

Science.gov (United States)

Bridges, Thomas J.; Donaldson, Neil M.

2007-07-01

A geometric view of criticality for two-layer flows is presented. Uniform flows are classified by diagrams in the momentum-massflux space for fixed Bernoulli energy, and cuspoidal curves on these diagrams correspond to critical uniform flows. Restriction of these surfaces to critical flow leads to new subsurfaces in energy-massflux space. While the connection between criticality and the generation of solitary waves is well known, we find that the nonlinear properties of these bifurcating solitary waves are also determined by the properties of the criticality surfaces. To be specific, the case of two layers with a rigid lid is considered, and application of the theory to other multilayer flows is sketched.

Bmi-1 plays a critical role in the protection from acute tubular necrosis by mobilizing renal stem/progenitor cells

International Nuclear Information System (INIS)

Lv, Xianhui; Yu, Zhenzhen; Xie, Chunfeng; Dai, Xiuliang; Li, Qing; Miao, Dengshun; Jin, Jianliang

2017-01-01

The regeneration of injured tubular cell occurs primarily from intrinsic renal stem/progenitor cells (RSCs) labeled with CD24 and CD133 after acute tubular necrosis (ATN). Bmi-1 plays a crucial role in regulating self-renewal, differentiation and aging of multiple adult stem cells and progenitor cells. Bmi-1 was rapidly elevated in the induction of adult kidney regeneration by renal injury. To determine whether Bmi-1 maintained mobilization of RSCs in the protection from ATN, glycerol-rhabdomyolysis-induced ATN were performed in wild type (WT) and Bmi-1-deficient (Bmi-1 −/− ) mice. Their ATN phenotypes were analyzed; CD24 and CD133 double positive (CD24 + CD133 + ) cells were measured; and the levels of serum urea nitrogen (SUN) and serum creatinine (SCr) were detected. We found that CD24 + CD133 + RSCs were mobilized in WT ATN mice with the increased expression of Bmi-1; Bmi-1 deficiency led to increased tubular cast formation and necrosis, elevated levels of SUN and SCr, decreased tubular proliferation, and immobilized ratio of RSCs in ATN. These findings indicated that Bmi-1 played a critical role in the protection from ATN by maintaining mobilization of RSCs and would be a novel therapeutic target for preventing the progression of ATN.

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