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Sample records for human vap-c negatively

  1. VapC20 of Mycobacterium tuberculosis Cleaves the Sarcin Ricin Loop of 23S rRNA

    DEFF Research Database (Denmark)

    Winther, Kristoffer Skovbo; Brodersen, Ditlev E.; Brown, Alistair K

    2013-01-01

    The highly persistent and often lethal human pathogen, Mycobacterium tuberculosis contains at least 88 toxin–antitoxin genes. More than half of these encode VapC PIN domain endoribonucleases that inhibit cell growth by unknown mechanisms. Here we show that VapC20 of M. tuberculosis inhibits...... exhibited by M. tuberculosis. VapC20 cleavage is inhibited by mutations in the SRL that flank the cleavage site but not by changes elsewhere in the loop. Disruption of the SRL stem abolishes cleavage; however, further mutations that restore the SRL stem structure restore cleavage, revealing...

  2. Toxins vapC and pasB from prokaryotic TA modules remain active in mammalian cancer cells.

    Science.gov (United States)

    Wieteska, Łukasz; Skulimowski, Aleksander; Cybula, Magdalena; Szemraj, Janusz

    2014-09-30

    Among the great number of addictive modules which have been discovered, only a few have been characterized. However, research concerning the adoption of toxins from these systems shows their great potential as a tool for molecular biology and medicine. In our study, we tested two different toxins derived from class II addictive modules, pasAB from plasmid pTF-FC2 (Thiobacillus ferrooxidans) and vapBC 2829Rv (Mycobacterium tuberculosis), in terms of their usefulness as growth inhibitors of human cancer cell lines, namely KYSE 30, MCF-7 and HCT 116. Transfection of the pasB and vapC genes into the cells was conducted with the use of two different expression systems. Cellular effects, such as apoptosis, necrosis and changes in the cell cycle, were tested by applying flow cytometry with immunofluorescence staining. Our findings demonstrated that toxins VapC and PasB demonstrate proapoptotic activity in the human cancer cells, regardless of the expression system used. As for the toxin PasB, observed changes were more subtle than for the VapC. The level of expression for both the genes was monitored by QPCR and did not reveal statistically significant differences within the same cell line.

  3. Structural analysis of the active site architecture of the VapC toxin from Shigella flexneri

    DEFF Research Database (Denmark)

    Xu, Kehan; Dedic, Emil; Brodersen, Ditlev Egeskov

    2016-01-01

    RNAfMet in vivo. Here, we present crystal structures of active site catalytic triad mutants D7A, D7N, and D98N of the VapC toxin in absence of antitoxin. In all structures, as well as in solution, VapC forms a dimer. In the D98N structure, a Hepes molecule occupies both active sites of the dimer and comparison...... with the structure of RNase H bound to a DNA/RNA hybrid suggests that the Hepes molecule mimics the position of an RNA nucleotide in the VapC active site....

  4. VapC toxins from Mycobacterium tuberculosis are ribonucleases that differentially inhibit growth and are neutralized by cognate VapB antitoxins.

    Directory of Open Access Journals (Sweden)

    Bintou Ahmadou Ahidjo

    Full Text Available The chromosome of Mycobacterium tuberculosis (Mtb encodes forty seven toxin-antitoxin modules belonging to the VapBC family. The role of these modules in the physiology of Mtb and the function(s served by their expansion are unknown. We investigated ten vapBC modules from Mtb and the single vapBC from M. smegmatis. Of the Mtb vapCs assessed, only Rv0549c, Rv0595c, Rv2549c and Rv2829c were toxic when expressed from a tetracycline-regulated promoter in M. smegmatis. The same genes displayed toxicity when conditionally expressed in Mtb. Toxicity of Rv2549c in M. smegmatis correlated with the level of protein expressed, suggesting that the VapC level must exceed a threshold for toxicity to be observed. In addition, the level of Rv2456 protein induced in M. smegmatis was markedly lower than Rv2549c, which may account for the lack of toxicity of this and other VapCs scored as 'non-toxic'. The growth inhibitory effects of toxic VapCs were neutralized by expression of the cognate VapB as part of a vapBC operon or from a different chromosomal locus, while that of non-cognate antitoxins did not. These results demonstrated a specificity of interaction between VapCs and their cognate VapBs, a finding corroborated by yeast two-hybrid analyses. Deletion of selected vapC or vapBC genes did not affect mycobacterial growth in vitro, but rendered the organisms more susceptible to growth inhibition following toxic VapC expression. However, toxicity of 'non-toxic' VapCs was not unveiled in deletion mutant strains, even when the mutation eliminated the corresponding cognate VapB, presumably due to insufficient levels of VapC protein. Together with the ribonuclease (RNase activity demonstrated for Rv0065 and Rv0617--VapC proteins with similarity to Rv0549c and Rv3320c, respectively--these results suggest that the VapBC family potentially provides an abundant source of RNase activity in Mtb, which may profoundly impact the physiology of the organism.

  5. VapC Toxins from Mycobacterium tuberculosis Are Ribonucleases that Differentially Inhibit Growth and Are Neutralized by Cognate VapB Antitoxins

    Science.gov (United States)

    Ahidjo, Bintou Ahmadou; Kuhnert, Diane; McKenzie, Joanna L.; Machowski, Edith E.; Gordhan, Bhavna G.; Arcus, Vickery; Abrahams, Garth L.; Mizrahi, Valerie

    2011-01-01

    The chromosome of Mycobacterium tuberculosis (Mtb) encodes forty seven toxin-antitoxin modules belonging to the VapBC family. The role of these modules in the physiology of Mtb and the function(s) served by their expansion are unknown. We investigated ten vapBC modules from Mtb and the single vapBC from M. smegmatis. Of the Mtb vapCs assessed, only Rv0549c, Rv0595c, Rv2549c and Rv2829c were toxic when expressed from a tetracycline-regulated promoter in M. smegmatis. The same genes displayed toxicity when conditionally expressed in Mtb. Toxicity of Rv2549c in M. smegmatis correlated with the level of protein expressed, suggesting that the VapC level must exceed a threshold for toxicity to be observed. In addition, the level of Rv2456 protein induced in M. smegmatis was markedly lower than Rv2549c, which may account for the lack of toxicity of this and other VapCs scored as ‘non-toxic’. The growth inhibitory effects of toxic VapCs were neutralized by expression of the cognate VapB as part of a vapBC operon or from a different chromosomal locus, while that of non-cognate antitoxins did not. These results demonstrated a specificity of interaction between VapCs and their cognate VapBs, a finding corroborated by yeast two-hybrid analyses. Deletion of selected vapC or vapBC genes did not affect mycobacterial growth in vitro, but rendered the organisms more susceptible to growth inhibition following toxic VapC expression. However, toxicity of ‘non-toxic’ VapCs was not unveiled in deletion mutant strains, even when the mutation eliminated the corresponding cognate VapB, presumably due to insufficient levels of VapC protein. Together with the ribonuclease (RNase) activity demonstrated for Rv0065 and Rv0617 – VapC proteins with similarity to Rv0549c and Rv3320c, respectively – these results suggest that the VapBC family potentially provides an abundant source of RNase activity in Mtb, which may profoundly impact the physiology of the organism. PMID:21738782

  6. Human choice under schedules of negative reinforcement.

    Science.gov (United States)

    Alessandri, Jérôme; Cançado, Carlos R X

    2015-12-01

    The generalized matching equation provides a good description of response allocation in concurrent schedules of positive reinforcement in nonhumans as well as in humans. The present experiment was conducted to further investigate the allocation of responding under concurrent schedules of negative reinforcement (i.e., timeouts from pressing a force cell) in humans. Each of three participants was exposed to different reinforcement ratios (9:1, 1:1 and 1:9) in the terminal links of a concurrent-chains schedule of negative reinforcement. The allocation of responding under this schedule was well described by the generalized matching equation, for each participant. These results replicate previous findings obtained with nonhumans and humans under concurrent schedules of positive reinforcement. In addition, they extend the results reported by Alessandri and Rivière (2013) showing that human behavior maintained by timeouts from an effortful response is sensitive to changes in relative reinforcement ratios as well as relative delays of reinforcement. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. MECHANISMS TO AMELIORATE NEGATIVE IMPACTS OF GLOBALISATION ON HUMAN RESOURCES, INDUSTRIAL DEMOCRACY AND HUMANITY

    OpenAIRE

    WILFRED I. UKPERE

    2009-01-01

    Capitalist globalisation has produced certain negative consequences for human resources, industrial democracy and humanity, in general. Globalisation is a powerful force that cannot be denied, however, conversely, it has also threatened life, in a broader sense. Globalisation was perceived by globalisers as a worldwide remedy for worldwide problems, but is viewed with great pessimism amongst proletariat (workers). Current globalisation has an enormous negative impact on human resources, indus...

  8. Negative emotion can enhance human motor cortical plasticity.

    Science.gov (United States)

    Koganemaru, Satoko; Domen, Kazuhisa; Fukuyama, Hidenao; Mima, Tatsuya

    2012-05-01

    Although emotion often primes us for action, its effects on the human motor system are not well understood. The relationship between emotion and motor plasticity also remains unclear, despite the close link between emotion and memory formation. Here, we tested the hypothesis that emotion modulates the plasticity of the human primary motor cortex, using the International Affective Picture System and transcranial magnetic stimulation. Intermittent theta-burst stimulation was applied to the primary motor cortex to produce long-term potentiation-like changes in normal volunteers experimentally. Primary motor cortex plasticity was enhanced and sustained in both excitatory and inhibitory systems only when intermittent theta-burst stimulation was combined with the presentation of pictures that induced negative, but not positive or neutral, emotion. Moreover, negative emotion was found to enhance the inhibitory networks within the primary motor cortex, and to improve motor behavior during the choice reaction-time task. Our findings indicate that negative emotion can increase primary motor cortex plasticity by modulating the intracortical GABAergic system, as well as N-methyl-d-aspartic acid receptor-dependent changes. These findings could help to explain the physiological basis of abnormal motor symptoms in psychogenic movement disorders following emotional events. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  9. Merlin is a negative regulator of human melanoma growth.

    Science.gov (United States)

    Murray, Lucas B; Lau, Ying-Ka Ingar; Yu, Qin

    2012-01-01

    Merlin is encoded by the neurofibromatosis type 2 (NF2) gene and is a member of the Band 4.1 protein family. This protein acts as a linker that connects cell surface proteins to the actin cytoskeleton. Defects caused by mutations of the NF2 gene give rise to NF2 disease, which is generally characterized by the formation of bilateral vestibular schwannomas and, to a lesser extent, meningiomas and ependymomas. In addition to these tumor types, NF2 is mutated and/or merlin expression is reduced or lost in numerous non-NF2 associated tumors, including melanoma. However, the role of merlin in human melanoma growth and the mechanism underlying its effect are currently unknown. In the present study, we show that merlin knockdown enhances melanoma cell proliferation, migration, and invasion in vitro and that decreased merlin expression promotes subcutaneous melanoma growth in immunocompromised mice. Concordantly, we find that increased expression of merlin in a metastatic melanoma cell line reduced their in vitro migration and proliferation, and diminished their ability to grow in an anchorage independent manner. Increased merlin expression also inhibits in vivo growth of these melanoma cells. Lastly, we demonstrate that higher merlin levels in human melanoma cells promote the H(2)O(2)-induced activation of MST1/2 Ser/Thr kinases, which are known tumor suppressors in the Hippo signaling pathway. Taken together, these results provide for the first time evidence that merlin negatively regulates human melanoma growth, and that loss of merlin, or impaired merlin function, results in an opposite effect. In addition, we show that increased merlin expression leads to enhanced activation of the MTS1/2 kinases, implying the potential roles of MST1/2 in mediating the anti-melanoma effects of merlin.

  10. MDM2 negatively regulates the human telomerase RNA gene promoter

    Directory of Open Access Journals (Sweden)

    Keith W Nicol

    2005-01-01

    Full Text Available Abstract Background We have previously demonstrated that NF-Y and Sp1 interact with the human telomerase RNA (hTR promoter and play a central role in its regulation. We have also shown that pRB activates the hTR promoter, but the mechanism of pRb directed activation is unknown. It has recently been reported that pRB induces Sp1 activity by relieving inhibition mediated by mdm2. The aim was to investigate possible roles for mdm2 in hTR promoter regulation. Methods Chromatin immunoprecipitation was used to determine binding of mdm2 to the hTR promoter. Transfection and luciferase assays were used to investigate mdm2 repression of the promoter activity and interaction with known transcriptional modulators. Results Here we show using chromatin immunoprecipitation that mdm2 specifically binds the hTR promoter in vivo. Transient co-transfection experiments using an hTR promoter luciferase reporter construct show that hTR promoter activity is inhibited by over-expression of mdm2 in 5637 bladder carcinoma cells (p53 and pRB negative, low mdm2. Titration of mdm2 was able to antagonise activation of hTR promoter activity mediated by pRB or Sp1 over-expression, although in the presence of pRB, mdm2 could not repress promoter activity below basal levels. Using an Sp1 binding site mutation construct we showed that mdm2 repression did not absolutely require Sp1 binding sites in the hTR promoter, suggesting the possibility of pRB/Sp1 independent mechanisms of repression. Finally, we show that NF-Y mediated transactivation of the hTR promoter was also suppressed by mdm2 in a dose-dependent manner. Conclusions These studies suggest that mdm2 may inhibit the hTR promoter by multiple mechanisms. Mdm2 may directly repress activation by both pRB and Sp1, or activation by NF-Y. Furthermore, the ability of mdm2 to interact and interfere with components of the general transcription machinery might partly explain the general repressive effect seen here. Elucidation of

  11. Human Discs Large is a new negative regulator of human immunodeficiency virus-1 infectivity.

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    Perugi, Fabien; Muriaux, Delphine; Ramirez, Bertha Cecilia; Chabani, Sabah; Decroly, Etienne; Darlix, Jean-Luc; Blot, Vincent; Pique, Claudine

    2009-01-01

    Human immunodeficiency virus (HIV)-1 replication is positively or negatively regulated through multiple interactions with host cell proteins. We report here that human Discs Large (Dlg1), a scaffold protein recruited beneath the plasma membrane and involved in the assembly of multiprotein complexes, restricts HIV-1 infectivity. The endogenous Dlg1 and HIV-1 Gag polyprotein spontaneously interact in HIV-1-chronically infected T cells. Depleting endogenous Dlg1 in either adherent cells or T cells does not affect Gag maturation, production, or release, but it enhances the infectivity of progeny viruses five- to sixfold. Conversely, overexpression of Dlg1 reduces virus infectivity by approximately 80%. Higher virus infectivity upon Dlg1 depletion correlates with increased Env content in cells and virions, whereas the amount of virus-associated Gag or genomic RNA remains identical. Dlg1 knockdown is also associated with the redistribution and colocalization of Gag and Env toward CD63 and CD82 positive vesicle-like structures, including structures that seem to still be connected to the plasma membrane. This study identifies both a new negative regulator that targets the very late steps of the HIV-1 life cycle, and an assembly pathway that optimizes HIV-1 infectivity.

  12. Pharmacokinetics and anti-HIV-1 efficacy of negatively charged human serum albumins in mice

    NARCIS (Netherlands)

    Kuipers, M E; Swart, P J; Schutten, Martin; Smit, C; Proost, J H; Osterhaus, A D; Meijer, D K

    Negatively charged albumins (NCAs, with the prototypes succinylated human serum albumin (Suc-HSA) and aconitylated human serum albumin (Aco-HSA)), modified proteins with a potent anti-human immunodeficiency virus type 1 (anti-HIV-1) activity in vitro, were studied for their pharmacokinetic behaviour

  13. Exploratory Investigation into Influence of Negative Attitudes toward Robots on Human-Robot Interaction

    OpenAIRE

    Nomura, Tatsuya; Kanda, Takayuki; Suzuki, Tomohiro; KATO, Kensuke

    2006-01-01

    This chapter provided the concept of negative attitudes toward robots and a measurement method for them, "Negative Attitudes toward Robots Scale (NARS)", as a psychological index in research on human-robot interaction. Then, it showed the results of some experiments and social research by using this psychological scale. The results implicated by the NARS show the efficiency of this scale in both human-robot interaction experiments and social research. They revealed that attitudes toward robot...

  14. The Human Ventromedial Frontal Lobe Is Critical for Learning from Negative Feedback

    Science.gov (United States)

    Wheeler, Elizabeth Z.; Fellows, Lesley K.

    2008-01-01

    Are positive and negative feedback weighed in a common balance in the brain, or do they influence behaviour through distinct neural mechanisms? Recent neuroeconomic studies in both human and non-human primates indicate that the ventromedial frontal lobe carries information about both losses and gains, suggesting that this region may encode value…

  15. Negatively-charged air conditions and responses of the human psycho-neuro-endocrino-immune network.

    Science.gov (United States)

    Takahashi, Kazuaki; Otsuki, Takemi; Mase, Akinori; Kawado, Takashi; Kotani, Muneo; Ami, Kazuhisa; Matsushima, Hiroki; Nishimura, Yasumitsu; Miura, Yoshie; Murakami, Shuko; Maeda, Megumi; Hayashi, Hiroaki; Kumagai, Naoko; Shirahama, Takashi; Yoshimatsu, Michiharu; Morimoto, Kanehisa

    2008-08-01

    Against increasing environmental adverse effects on human health such as those associated with water and ground pollution, as well as out- and indoor air conditions, trials were conducted to support and promote human health by improving the indoor air atmosphere. This study was performed to estimate the effect of negatively-charged air conditions on human biological markers related to the psycho-neuro-endocrino-immune (PNEI) network. After construction of negatively-charged experimental rooms (NCRs), healthy volunteers were admitted to these rooms and control rooms (CTRs) and various biological responses were analyzed. NCRs were constructed using a fine charcoal coating and applying an electric voltage (72 V) between the backside of walls and the ground. Various biological markers were monitored that related to general conditions, autonomic nervous systems, stress markers, immunological parameters and blood flow. Regarding the indoor environment, only negatively-charged air resulted in the difference between the CTR and NCR groups. The well-controlled experimental model-room to examine the biological effects of negatively-charged air was therefore established. Among the various parameters, IL-2, IL-4, the mean RR interval of the heart rate, and blood viscosity differed significantly between the CTR and NCR groups. In addition, the following formula was used to detect NCR-biological responses: Biological Response Value (BRV)=0.498+0.0005 [salivary cortisol]+0.072 [IL-2]+0.003 [HRM-SD]-0.013 [blood viscosity]-0.009 [blood sugar]+0.017 [pulse rate]. Negatively-charged air conditions activated the immune system slightly, smoothened blood flow and stabilized the autonomic nervous system. Although this is the first report to analyze negatively-charged air conditions on human biological responses, the long-term effects should be analyzed for the general use of these artificial atmospheres.

  16. Trends and Determinants of Human Papillomavirus Concordance Among Human Immunodeficiency Virus-Positive and -Negative Heterosexual Couples in Rakai, Uganda.

    Science.gov (United States)

    Grabowski, Mary K; Gravitt, Patti E; Gray, Ronald H; Serwadda, David; Redd, Andrew D; Kigozi, Godfrey; Kong, Xiangrong; Nalugoda, Fred; Wawer, Maria J; Quinn, Thomas C; Tobian, Aaron A R

    2017-03-01

    Limited data are available on human papillomavirus (HPV) infection among human immunodeficiency virus (HIV)-negative or HIV-positive couples followed longitudinally. Genital HPV was assessed in 725 concordant HIV-negative couples and 209 HIV-positive couples enrolled in a male circumcision trial in Rakai, Uganda, using the Roche Linear Array assay, which detects 37 HPV genotypes. Human papillomavirus prevalence and determinants of genotype-specific concordance were assessed at annual visits. Cumulative detection of HPV genotypes over 2 years was also assessed. At enrollment, HPV infection was detected in 54% of HIV-negative women, 56% of HIV-negative men, and 93% of HIV-positive men and women. For HIV-negative couples, genotypic concordance was 30% at baseline (n = 219/725) and declined significantly with age (adjusted prevelance risk ratio [adjPRR] = 0.53; 95% confidence interval [CI] = 0.28-0.93 comparing women aged >40 years to those aged 15-19 years) and male circumcision (adjPRR = 0.60; 95% CI = 0.47-0.77) and increased among couples with recent intercourse (adjPRR = 1.26; 95% CI = 1.04-1.53). These associations were not seen in HIV-positive couples. Among couples with HPV results at all visits, ≥1 of the same genotypes were detected in both partners in 60% of HIV-negative couples and 96% of HIV-positive couples over 2 years. Human papillomavirus genotype-specific concordance is more common in HIV-positive couples, and irrespective of HIV status, the majority of couples exhibit HPV concordance over 2 years.

  17. Polio vaccines, SV40 and human tumours, an update on false positive and false negative results.

    Science.gov (United States)

    Elmishad, A G; Bocchetta, M; Pass, H I; Carbone, M

    2006-01-01

    Simian virus 40 (SV40) has been detected in different human tumours in numerous laboratories. The detection of SV40 in human tumours has been linked to the administration of SV40-contaminated polio vaccines from 1954 until 1963. Many of these reports linked SV40 to human mesothelioma. Some studies have failed to detect SV40 in human tumours and this has caused a controversy. Here we review the current literature. Moreover, we present evidence showing how differences in the sensitivities of methodologies can lead to a very different interpretation of the same study. The same 20 mesothelioma specimens all tested negative, 2/20 tested positive or 7/20 tested positive for SV40 Tag by simply changing the detection method on the same immuno-precipitation/western blot membranes. These results provide a simple explanation for some of the apparent discordant results reported in the literature.

  18. Factors That Influence Human Behavior And Negatively Affect Energy Consumption In USMC Ground Units During Operations

    Science.gov (United States)

    2016-09-01

    February 2011 the Marine Corps published its Expeditionary Energy Strategy and Implementation Plan to reduce dependence on fossil fuels in the operational...inefficiently used and consequently consumed more energy than necessary. The scenarios observed can be grouped in two categories referred to as excessive...INFLUENCE HUMAN BEHAVIOR AND NEGATIVELY AFFECT ENERGY CONSUMPTION IN USMC GROUND UNITS DURING OPERATIONS by John A. Peters September 2016

  19. Detection of sexually transmitted infection and human papillomavirus in negative cytology by multiplex-PCR

    Directory of Open Access Journals (Sweden)

    Chung Hyun-Jae

    2010-09-01

    Full Text Available Abstract Background The aim of this study was to determine the prevalence of human papillomavirus (HPV and 15 species that cause sexually transmitted infections (STIs in negative cytology. In addition, we compared the diagnostic performance of multiplex polymerase chain reaction (PCR with widely available techniques used to detect HPV. Methods We recruited 235 women of reproductive age who had negative cytology findings in a liquid-based cervical smear. STIs were identified by multiplex PCR, and HPV genotypes by multiplex PCR, hybrid capture 2, and DNA microaray; discordant results were analyzed by direct sequencing. Results Approximately 96.6% of patients with negative cytology results were positive for pathogens that cause STIs. The pathogens most frequently detected were Gardnerella vaginalis, Ureaplasma urealyticum. The incidence of HPV in negative cytology was 23.3%. Low-risk HPV infection was significantly correlated with Chalmaydia trachomatis, and high-risk HPV infection was significantly correlated with Group β streptococcus. The analytical sensitivities of the multiplex PCR and DNA microarray were higher than 80%, and the analytical specificity was nearly 100% for all tests. Conclusions Multiplex PCR yielded results that most of patients with negative cytology were positive for pathogens that cause STIs, and were more similar to that of DNA microarray, than that of hybrid capture 2 in terms of analytical sensitivity and prediction value of HPV infection.

  20. A Novel Generalized Normal Distribution for Human Longevity and other Negatively Skewed Data

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    Robertson, Henry T.; Allison, David B.

    2012-01-01

    Negatively skewed data arise occasionally in statistical practice; perhaps the most familiar example is the distribution of human longevity. Although other generalizations of the normal distribution exist, we demonstrate a new alternative that apparently fits human longevity data better. We propose an alternative approach of a normal distribution whose scale parameter is conditioned on attained age. This approach is consistent with previous findings that longevity conditioned on survival to the modal age behaves like a normal distribution. We derive such a distribution and demonstrate its accuracy in modeling human longevity data from life tables. The new distribution is characterized by 1. An intuitively straightforward genesis; 2. Closed forms for the pdf, cdf, mode, quantile, and hazard functions; and 3. Accessibility to non-statisticians, based on its close relationship to the normal distribution. PMID:22623974

  1. A Developmental Shift from Positive to Negative Connectivity in Human Amygdala-Prefrontal Circuitry

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    Gee, Dylan G.; Humphreys, Kathryn L.; Flannery, Jessica; Goff, Bonnie; Telzer, Eva H.; Shapiro, Mor; Hare, Todd A.; Bookheimer, Susan Y.; Tottenham, Nim

    2013-01-01

    Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. While tracing studies have suggested changes in amygdala-cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala-prefrontal circuitry across the ages of 4 to 22 years using task-based functional magnetic resonance imaging (fMRI). Results suggest positive amygdala-prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala-mPFC functional connectivity was significantly positive (greater than zero) among participants younger than ten, whereas functional connectivity was significantly negative (less than zero) among participants ten years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections. PMID:23467374

  2. Are we ignoring neutral and negative human-animal relationships in zoos?

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    Hosey, Geoff; Melfi, Vicky

    2015-01-01

    Human-animal interactions (HAI), which may lead to human-animal relationships (HAR), may be positive, neutral, or negative in nature. Zoo studies show that visitors may be stressful, may have no effect, or may be enriching. There is also evidence that good HARs set up between animals and their keepers can have positive effects on animal welfare. However, we need to know more about negative HARs, and as a first step we attempt to do this here by considering cases where animals attack people in the zoo. Due to the sensitivity and rarity of these events data appear sparse and unsystematically collected. Here, information available in the public domain about the circumstances of these attacks has been collated to test hypotheses about negative HAIs derived from a model of zoo HARs. The limited data presented here broadly support the zoo HAR model, and suggest that attacks usually happen in unusual circumstances, where there may be a failure by the animal to recognise the HAR, or where the relationship, if there is one, does not hold; and give some support to the prediction that exposure to many keepers may impair the development of a positive HAR. This study may provide useful information for the zoo community to proactively collect systematic standardised records, which will enable a fuller understanding of zoo HARs, upon which appropriate measures might be adopted to build better zoo HARs, which are likely to positively impact zoo animal welfare, and reduce these rare incidences further. © 2014 Wiley Periodicals, Inc.

  3. Epigenetic differences between human papillomavirus-positive and -negative oropharyngeal squamous cell carcinomas.

    Science.gov (United States)

    Biron, Vincent L; Mohamed, Adil; Hendzel, Michael J; Alan Underhill, D; Seikaly, Hadi

    2012-04-01

    Epigenetic modifications are defined as heritable changes in gene expression that are not encoded in deoxyribonucleic acid (DNA). Despite the importance of epigenetics in tumorigenesis, there is a paucity of information regarding the epigenetic profiles of oropharyngeal squamous cell carcinoma (OPSCC). The objective of this study was to identify epigenetic signatures associated with human papillomavirus (HPV)-positive and -negative OPSCC. We collected demographic, pathologic, and survival data from 44 patients with advanced-stage OPSCC treated with surgery and chemoradiation at the University of Alberta between January 2006 and December 2008. Tumour specimen from these patients were retreived and sectioned for immunohistochemical analysis. Double immunofluorescence staining was performed with p16 (HPV surrogate) and a panel of epigenetic markers, namely, histone methyl-lysines 4, 9, and 27 and H4 methyl-lysine 20. Correlation between p16 and epigenetic markers was measured using Metamorph and Image J software. Forty-one percent of patients were p16 positive. No statistically significant differences were found between p16-positive and -negative patients in terms of age at diagnosis, tumour subsite, or smoking history. We found significant differences in histone methylation between p16-positive and -negative tumours. OPSCC tumours positive for p16 had global elevations of histone H4 monomethylated lysine 20 (H4K20me1) and H3 trimethylated lysine 27 (H3K27me3) with depletions of H4 trimethylated lysine 20 (H4K20me3). In contrast, p16-negative tumours had depleted levels of H4K20me1 and H3K27me3 with high levels of H4K20me3. HPV-positive and -negative OPSCCs have distinct epigenetic profiles representing broad gene expression differences between these tumours.

  4. Positive and negative regulation of the human heme oxygenase-1 gene expression in cultured cells.

    Science.gov (United States)

    Takahashi, S; Takahashi, Y; Ito, K; Nagano, T; Shibahara, S; Miura, T

    1999-10-28

    To elucidate the regulation of the human heme oxygenase-1 (hHO-1) gene expression, we assessed approximately 4 kb of the 5'-flanking region of the hHO-1 gene for basal promoter activity and sequenced approximately 2 kb of the 5'-flanking region. A series of deletion mutants of the 5'-flanking region linked to the luciferase gene was constructed. Basal level expression of these constructs was tested in HepG2 human hepatoma cells and HeLa cervical cancer cells. By measuring luciferase activity, which was transiently expressed in the transfected cells, we found a positive regulatory region at position -1976 to -1655 bp. This region functions in HepG2 cells but not in HeLa cells. A negative regulatory region was also found at position -981 to -412 bp that functions in both HepG2 cells and HeLa cells.

  5. Negative Emissions Technologies, the Paris Agreement, and the Need for a Human-Rights Based Approach

    Science.gov (United States)

    Burns, W. C. G.

    2016-12-01

    The new Paris Agreement under the United Nations Framework Convention on Climate Change contemplates that its prospective Parties will balance emissions and sinks by 2050 as a means to effectuate the goal of holding temperature increases to well below 2°C from pre-industrial levels, as well as the more aspirational goal of holding temperature increases to 1.5°C. Most of the IPCC's AR5 scenarios that achieve these objectives contemplate the large-scale deployment of so-called "negative emissions technologies," with an emphasis on bioenergy and carbon capture and storage (BECCS), and to a lesser degree afforestation. BECCS could assuredly help society avoid passing critical climatic thresholds, or address overshoot scenarios in this century and beyond. However, it could also profound implications for food production, the status of forests, access to lands for livelihoods by vulnerable populations, and the integrity of critical ecosystems. This, in turn could have serious ramifications for human rights of some of the world's most vulnerable populations, including the rights to food, water, livelihoods and the benefits of biodiversity. The Preamble to the Paris Agreement acknowledges the need to take into consideration the potential impact of responses to climate change, providing that "Parties should, when taking action to address climate change, respect, promote and consider their respective obligations on human rights." This presentation will outline how application of a human rights-based approach to assessing such options could help to reconcile the objectives of ameliorating potential climatic impacts while protecting the human rights of potentially affected individuals and groups. This will include the potential role of Human Rights Impacts Assessments and potential configuration of HRIAs at the national and international level. It will also briefly suggest how to operationalize this approach within the Paris Agreement framework, including institutional

  6. Laminar imaging of positive and negative BOLD in human visual cortex at 7T.

    Science.gov (United States)

    Fracasso, Alessio; Luijten, Peter R; Dumoulin, Serge O; Petridou, Natalia

    2017-02-14

    Deciphering the direction of information flow is critical to understand the brain. Data from non-human primate histology shows that connections between lower to higher areas (e.g. retina→V1), and between higher to lower areas (e.g. V1←V2) can be dissociated based upon the distribution of afferent synapses at the laminar level. Ultra-high field scanners opened up the possibility to image brain structure and function at an unprecedented level of detail. Taking advantage of the increased spatial resolution available, it could theoretically be possible to disentangle activity from different cortical depths from human cerebral cortex, separately studying different compartments across depth. Here we use half-millimeter human functional and structural magnetic resonance imaging (fMRI, MRI) to derive laminar profiles in early visual cortex using a paradigm known to elicit two separate responses originating from an excitatory and a suppressive source, avoiding any contamination due to blood-stealing. We report the shape of laminar blood level oxygenation level dependent (BOLD) profiles from the excitatory and suppressive conditions. We analyse positive and negative %BOLD laminar profiles with respect to the dominating linear trend towards the pial surface, a confounding feature of gradient echo BOLD fMRI, and examine the correspondence with the anatomical landmark of input-related signals in primary visual cortex, the stria of Gennari. Copyright © 2017. Published by Elsevier Inc.

  7. Negative Facial Expressions - But Not Visual Scenes - Enhance Human Working Memory in Younger and Older Participants.

    Science.gov (United States)

    Belham, Flávia Schechtman; Tavares, Maria Clotilde H; Satler, Corina; Garcia, Ana; Rodrigues, Rosângela C; Canabarro, Soraya L de Sá; Tomaz, Carlos

    2017-01-01

    Many studies have investigated the influence of emotion on memory processes across the human lifespan. Some results have shown older adults (OA) performing better with positive stimuli, some with negative items, whereas some found no impact of emotional valence. Here we tested, in two independent studies, how younger adults (YA) and OA would perform in a visuospatial working memory (VSWM) task with positive, negative, and neutral images. The task consisted of identifying the new location of a stimulus in a crescent set of identical stimuli presented in different locations in a touch-screen monitor. In other words, participants should memorize the locations previously occupied to identify the new location. For each trial, the number of occupied locations increased until 8 or until a mistake was made. In study 1, 56 YA and 38 OA completed the task using images from the International Affective Picture System (IAPS). Results showed that, although YA outperformed OA, no effects of emotion were found. In study 2, 26 YA and 25 OA were tested using facial expressions as stimuli. Data from this study showed that negative faces facilitated performance and this effect did not differ between age groups. No differences were found between men and women. Taken together, our findings suggest that YA and OA's VSWM can be influenced by the emotional valence of the information, though this effect was present only for facial stimuli. Presumably, this may have happened due to the social and biological importance of such stimuli, which are more effective in transmitting emotions than IAPS images. Critically, our results also indicate that the mixed findings in the literature about the influence of aging on the interactions between memory and emotion may be caused by the use of different stimuli and methods. This possibility should be kept in mind in future studies about memory and emotion across the lifespan.

  8. Targeting autophagic cancer stem-cells to reverse chemoresistance in human triple negative breast cancer.

    Science.gov (United States)

    Bousquet, Guilhem; El Bouchtaoui, Morad; Sophie, Tan; Leboeuf, Christophe; de Bazelaire, Cédric; Ratajczak, Philippe; Giacchetti, Sylvie; de Roquancourt, Anne; Bertheau, Philippe; Verneuil, Laurence; Feugeas, Jean-Paul; Espié, Marc; Janin, Anne

    2017-05-23

    There is growing evidence for the role of cancer stem-cells in drug resistance, but with few in situ studies on human tumor samples to decipher the mechanisms by which they resist anticancer agents.Triple negative breast cancer (TNBC) is the most severe sub-type of breast cancer, occurring in younger women and associated with poor prognosis even when treated at a localized stage.We investigated here the relationship between complete pathological response after chemotherapy and breast cancer stem-cell characteristics in pre-treatment biopsies of 78 women with triple negative breast carcinoma (TNBC).We found that chemoresistance was associated with large numbers of breast cancer stem-cells, and that these cancer stem-cells were neither proliferative nor apoptotic, but in an autophagic state related to hypoxia. Using relevant pharmacological models of patient-derived TNBC xenografts, we further investigated the role of autophagy in chemoresistance of breast cancer stem-cells. We demonstrated that hypoxia increased drug resistance of autophagic TNBC stem-cells, and showed that molecular or chemical inhibition of autophagic pathway was able to reverse chemoresistance.Our results support breast cancer stem-cell evaluation in pre-treatment biopsies of TNBC patients, and the need for further research on autophagy inhibition to reverse resistance to chemotherapy.

  9. Human Commercial Models' Eye Colour Shows Negative Frequency-Dependent Selection.

    Science.gov (United States)

    Forti, Isabela Rodrigues Nogueira; Young, Robert John

    2016-01-01

    In this study we investigated the eye colour of human commercial models registered in the UK (400 female and 400 male) and Brazil (400 female and 400 male) to test the hypothesis that model eye colour frequency was the result of negative frequency-dependent selection. The eye colours of the models were classified as: blue, brown or intermediate. Chi-square analyses of data for countries separated by sex showed that in the United Kingdom brown eyes and intermediate colours were significantly more frequent than expected in comparison to the general United Kingdom population (PBrazilian population. These results support the hypothesis that model eye colour is the result of negative frequency-dependent selection. This could be the result of people using eye colour as a marker of genetic diversity and finding rarer eye colours more attractive because of the potential advantage more genetically diverse offspring that could result from such a choice. Eye colour may be important because in comparison to many other physical traits (e.g., hair colour) it is hard to modify, hide or disguise, and it is highly polymorphic.

  10. Control algorithm of lighting color for LED considering human's negative feeling

    Science.gov (United States)

    Yamagishi, Yoko; Mita, Akira

    2014-03-01

    This research looks for appropriate colors of lighting depending on several kinds of feelings, covering not only colors which are on trajectory of a complete radiator but also other various colors, and aims to propose a control algorithm of lighting color of LED considering human's negative feelings. This research consists of three experiments. The first experiment aims to seek an appropriate color of lighting when we feel anger, sadness, happy and joy. The second experiment is to seek for reasons of results of the first experiment and to look for what kind of impression of lighting color leads to comfortable lighting environment. The third experiment aims to look for an applicable control of lighting colors when considering people's feelings. From these experiments, it was found that comfortable lighting color differ depending on feelings and the possibility of an effective use of colors which are not on the trajectory of a complete radiator was shown. Moreover, many elements which lead to comfortable lighting control were found, and as the controlling method which consider those elements was more preferred than the method which does not change colors at all, the usability of controlling lighting colors considering people's negative feelings was proved.

  11. Characterization to species level of Mycobacterium avium complex strains from human immunodeficiency virus-positive and -negative patients.

    OpenAIRE

    Kyriakopoulos, A M; Tassios, P. T.; Matsiota-Bernard, P; Marinis, E; Tsaousidou, S; Legakis, N J

    1997-01-01

    Forty human clinical Mycobacterium avium-M. intracellulare complex strains isolated in Greece were characterized to the species level by PCR with three sets of primers specific for one or both species. M. avium predominated in both human immunodeficiency virus-positive and -negative patients, but the frequency of M. intracellulare isolation appeared to be higher in the latter.

  12. Gram-negative, but not Gram-positive, bacteria elicit strong PGE2 production in human monocytes.

    Science.gov (United States)

    Hessle, Christina C; Andersson, Bengt; Wold, Agnes E

    2003-12-01

    Gram-positive and Gram-negative bacteria induce different cytokine patterns in human mononuclear cells. We have seen that Gram-positives preferentially induce IL-12 and TNF-alpha, whereas Gram-negatives induce more IL-10, IL-6, and IL-8. In this study, we compared the capacity of these two groups of bacteria to induce PGE2. Monocytes stimulated with Gram-negative bacterial species induced much more PGE2 than did Gram-positive bacteria (5600 +/- 330 vs. 1700 +/- 670 pg/mL, p Gram-positive and Gram-negative bacteria. We suggest that Gram-positive and Gram-negative bacteria may stimulate different innate effector functions; Gram-positive bacteria promoting cell-mediated effector functions whereas Gram-negative bacteria inducing mediators inhibiting the same.

  13. False-negative urine human chorionic gonadotropin in molar pregnancy: " The high-dose hook effect" !

    Directory of Open Access Journals (Sweden)

    Sujata Narendra Datti

    2015-01-01

    Full Text Available Failure to detect pregnancy in the emergency situations can have important consequences. These include missing of ectopic pregnancy (the leading cause of first-trimester pregnancy-related maternal death, administration of medications contraindicated in pregnancy, fetal radiation exposure, and medico legal problems. This in turn has led to the dictum to check for pregnancy in all women of child-bearing age group. Urine pregnancy (human chorionic gonadotropin [hCG] test is the commonly used test to rule out pregnancy and has been reported by Griffey et al. in their study to achieve 100% sensitivity and 99.2% specificity in a clinical setting, resulting in a positive predictive value of 98.3% and a negative predictive value of nearly 100%. However, the sensitivity is influenced not only by the quantity of β hCG but on its variants that vary with different weeks of pregnancy. β hCG is present in several variant forms that change in their concentrations at different stages of pregnancy. In spite of its high sensitivity, in the presence of molar pregnancy that is associated with very high levels of β hCG it fails to detect the antigen (β hCG. This is explained by the phenomenon known as "high-dose hook effect" which further leads to delay in diagnosis and treatment. This can be overcome by dilution of the sample. In such cases, diagnosis will be made by serum β hCG and ultrasound (USG. Here, we present a case of gravida 2 para 1 living 1 with 2΍ months amenorrhea with bleeding p/v and pain abdomen of 20 days duration whose urine β hCG was repeatedly negative and diagnosis was made by serum β hCG and USG.

  14. Significant changes in sexual behavior after a diagnosis of human papillomavirus-positive and human papillomavirus-negative oral cancer.

    Science.gov (United States)

    Taberna, Miren; Inglehart, Ronald C; Pickard, Robert K L; Fakhry, Carole; Agrawal, Amit; Katz, Mira L; Gillison, Maura L

    2017-04-01

    Sexual behavior and oral human papillomavirus (HPV) infection are risk factors for oral squamous cell carcinoma (OSCC). The effects of OSCC diagnosis and treatment on subsequent relationship stress and sexual behavior are unknown. Incident cases of HPV-positive or HPV-negative OSCC in patients who had a partnered relationship and partners of patients with oropharyngeal cancer were eligible for a study in which surveys were administered at diagnosis and at the 6-month follow-up time point to assess relationship distress, HPV transmission and concerns about health consequences, and sexual behavior. The frequency distributions of responses, stratified by tumor HPV status, were compared at baseline and follow-up. In total, 262 patients with OSCC and 81 partners were enrolled. Among the patients, 142 (54.2%) had HPV-positive OSCC, and 120 (45.8%) had HPV-negative OSCC. Relationship distress was infrequently reported, and 69% of patients felt that their relationship had strengthened since the cancer diagnosis. Both HPV-positive patients (25%) and their partners (14%) reported feelings of guilt or responsibility for the diagnosis of an HPV-caused cancer. Concern over sexual, but not nonsexual, HPV transmission to partners was reported by 50%. Significant declines in the frequency of vaginal and oral sexual behaviors were reported at follow-up, regardless of tumor HPV status. From baseline to 6 months, significant increases in abstinence from vaginal sex (from 10% to 34%; P Sexual behavior is an important quality-of-life outcome to assess within clinical trials. [See related editorial on pages 000-000, this issue.] Cancer 2017. © 2017 American Cancer Society. Cancer 2017;123:1156-1165. © 2016 American Cancer Society. © 2017 American Cancer Society.

  15. Involvement of the modifier gene of a human Mendelian disorder in a negative selection process.

    Directory of Open Access Journals (Sweden)

    Isabelle Jéru

    Full Text Available BACKGROUND: Identification of modifier genes and characterization of their effects represent major challenges in human genetics. SAA1 is one of the few modifiers identified in humans: this gene influences the risk of renal amyloidosis (RA in patients with familial Mediterranean fever (FMF, a Mendelian autoinflammatory disorder associated with mutations in MEFV. Indeed, the SAA1 alpha homozygous genotype and the p.Met694Val homozygous genotype at the MEFV locus are two main risk factors for RA. METHODOLOGY/PRINCIPAL FINDINGS: HERE, WE INVESTIGATED ARMENIAN FMF PATIENTS AND CONTROLS FROM TWO NEIGHBORING COUNTRIES: Armenia, where RA is frequent (24%, and Karabakh, where RA is rare (2.5%. Sequencing of MEFV revealed similar frequencies of p.Met694Val homozygotes in the two groups of patients. However, a major deficit of SAA1 alpha homozygotes was found among Karabakhian patients (4% as compared to Armenian patients (24% (p = 5.10(-5. Most importantly, we observed deviations from Hardy-Weinberg equilibrium (HWE in the two groups of patients, and unexpectedly, in opposite directions, whereas, in the two control populations, genotype distributions at this locus were similar and complied with (HWE. CONCLUSIONS/SIGNIFICANCE: The excess of SAA1alpha homozygotes among Armenian patients could be explained by the recruitment of patients with severe phenotypes. In contrast, a population-based study revealed that the deficit of alpha/alpha among Karabakhian patients would result from a negative selection against carriers of this genotype. This study, which provides new insights into the role of SAA1 in the pathophysiology of FMF, represents the first example of deviations from HWE and selection involving the modifier gene of a Mendelian disorder.

  16. Cardiovascular regulation in humans in response to oscillatory lower body negative pressure

    Science.gov (United States)

    Levenhagen, D. K.; Evans, J. M.; Wang, M.; Knapp, C. F.

    1994-01-01

    The frequency response characteristics of human cardiovascular regulation during hypotensive stress have not been determined. We therefore exposed 10 male volunteers to seven frequencies (0.004-0.1 Hz) of oscillatory lower body negative pressure (OLBNP; 0-50 mmHg). Fourier spectra of arterial pressure (AP), central venous pressure (CVP), stroke volume (SV), cardiac output (CO), heart rate (HR), and total peripheral resistance (TPR) were determined and first harmonic mean, amplitude, and phase angles with respect to OLBNP are presented. AP was relatively well regulated as demonstrated by small oscillations in half amplitude (3.5 mmHg) that were independent of OLBNP frequency and similar to unstressed control spectra. Due to the biomechanics of the system, the magnitudes of oscillations in calf circumference (CC) and CVP decreased with increasing frequency; therefore, we normalized responses by these indexes of the fluid volume shifted. The ratios of oscillations in AP to oscillations in CC increased by an order of magnitude, whereas oscillations in CVP to oscillations in CC and oscillations in AP to oscillations in CVP both tripled between 0.004 and 0.1 Hz. Therefore, even though the amount of fluid shifted by OLBNP decreased with increasing frequency, the magnitude of both CVP and AP oscillations per volume of fluid shifted increased (peaking at 0.08 Hz). The phase relationships between variables, particularly the increasing lags in SV and TPR, but not CVP, indicated that efferent responses with lags of 5-6 s could account for the observed responses. We conclude that, at frequencies below 0.02 Hz, the neural system of humans functioned optimally in regulating AP; OLBNP-induced decreases in SV (by as much as 50%) were counteracted by appropriate oscillations in HR and TPR responses. As OLBNP frequency increased, SV, TPR, and HR oscillations increasingly lagged the input and became less optimally timed for AP regulation.

  17. Improving washing strategies of human mesenchymal stem cells using negative mode expanded bed chromatography.

    Science.gov (United States)

    Cunha, Bárbara; Silva, Ricardo J S; Aguiar, Tiago; Serra, Margarida; Daicic, John; Maloisel, Jean-Luc; Clachan, John; Åkerblom, Anna; Carrondo, Manuel J T; Peixoto, Cristina; Alves, Paula M

    2016-01-15

    The use of human mesenchymal stem cells (hMSC) in clinical applications has been increasing over the last decade. However, to be applied in a clinical setting hMSC need to comply with specific requirements in terms of identity, potency and purity. This study reports the improvement of established tangential flow filtration (TFF)-based washing strategies, further increasing hMSC purity, using negative mode expanded bed adsorption (EBA) chromatography with a new multimodal prototype matrix based on core-shell bead technology. The matrix was characterized and a stable, expanded bed could be obtained using standard equipment adapted from what is used for conventional packed bed chromatography processes. The effect of different expansion rates on cell recovery yield and protein removal capacity was assessed. The best trade-off between cell recovery (89%) and protein clearance (67%) was achieved using an intermediate expansion bed rate (1.4). Furthermore, we also showed that EBA chromatography can be efficiently integrated on the already established process for the downstream processing (DSP) of hMSC, where it improved the washing efficiency more than 10-fold, recovering approximately 70% of cells after global processing. This strategy showed not to impact cell viability (>95%), neither hMSC's characteristics in terms of morphology, immunophenotype, proliferation, adhesion capacity and multipotent differentiation potential. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Waddlia chondrophila, a Chlamydia-related bacterium, has a negative impact on human spermatozoa.

    Science.gov (United States)

    Baud, D; Vulliemoz, N; Ammerdorffer, A; Gyger, J; Greub, G; Castella, V; Stojanov, M

    2018-01-01

    What is the impact of Waddlia chondrophila, an emerging Chlamydia-related bacterium associated with miscarriage, on human spermatozoa? W. chondrophila had a negative impact on human spermatozoa (decrease in viability and mitochondrial membrane potential) and was not entirely removed from infected samples by density gradient centrifugation. Bacterial infection or colonization might have a deleterious effect on male fertility. Waddlia chondrophila was previously associated with miscarriage, but its impact on male reproductive function has never been studied. An in vitro model of human spermatozoa infection was used to assess the effects of W. chondrophila infection. Controls included Chlamydia trachomatis serovar D and latex beads with similar size to bacteria. Purified motile spermatozoa were infected with W. chondrophila (multiplicity of infection of 1). Immunohistochemistry combined with confocal microscopy was used to evaluate how bacteria interact with spermatozoa. The impact on physiology was assessed by monitoring cell viability, mitochondrial membrane potential and DNA fragmentation. Using super-resolution confocal microscopy, bacteria were localized on spermatozoa surface, as well as inside the cytoplasm. Compared to controls, W. chondrophila caused a 20% increase in mortality over 72 h of incubation (P < 0.05). Moreover, higher bacterial loads significantly reduced mitochondrial membrane potential. Bacteria present on spermatozoa surface were able to further infect a cell-monolayer, indicating that sperm might vector bacteria during sexual intercourse. The main limitation of the study is the use of an in vitro model of infection, which might be too simplistic compared to an actual infection. An animal model of infection should be developed to better evaluate the in vivo impact of W. chondrophila. Intracellular bacteria, including C. trachomatis, Mycoplasma spp. and Ureaplasma spp., are associated with male infertility. Waddlia chondrophila might represent

  19. Human attitudes towards herpetofauna: The influence of folklore and negative values on the conservation of amphibians and reptiles in Portugal

    Science.gov (United States)

    2012-01-01

    Background Human values and folklore of wildlife strongly influence the effectiveness of conservation efforts. These values and folklore may also vary with certain demographic characteristics such as gender, age, or education. Reptiles and amphibians are among the least appreciated of vertebrates and are victims of many negative values and wrong ideas resulting from the direct interpretation of folklore. We try to demonstrate how these values and folklore can affect the way people relate to them and also the possible conservation impacts on these animals. Methods A questionnaire survey distributed to 514 people in the district of Évora, Portugal, was used to obtain data regarding the hypothesis that the existence of wrong ideas and negative values contributes to the phenomenon of human-associated persecution of these animals. A structural equation model was specified in order to confirm the hypothesis about the possible relationships between the presence of perceptions and negative values about amphibians and reptiles and persecution and anti-conservation attitudes. Sociodemographic variables were also added. Results The results of the model suggest that the presence of folklore and negative values clearly predicts persecution and anti-conservation attitudes towards amphibians and reptiles. Also, the existence of folklore varies sociodemographically, but negative values concerning these animals are widespread in the population. Conclusions With the use of structural equation models, this work is a contribution to the study of how certain ideas and values can directly influence human attitudes towards herpetofauna and how they can be a serious conservation issue. PMID:22316318

  20. Human attitudes towards herpetofauna: the influence of folklore and negative values on the conservation of amphibians and reptiles in Portugal.

    Science.gov (United States)

    Ceríaco, Luis Mp

    2012-02-08

    Human values and folklore of wildlife strongly influence the effectiveness of conservation efforts. These values and folklore may also vary with certain demographic characteristics such as gender, age, or education. Reptiles and amphibians are among the least appreciated of vertebrates and are victims of many negative values and wrong ideas resulting from the direct interpretation of folklore. We try to demonstrate how these values and folklore can affect the way people relate to them and also the possible conservation impacts on these animals. A questionnaire survey distributed to 514 people in the district of Évora, Portugal, was used to obtain data regarding the hypothesis that the existence of wrong ideas and negative values contributes to the phenomenon of human-associated persecution of these animals. A structural equation model was specified in order to confirm the hypothesis about the possible relationships between the presence of perceptions and negative values about amphibians and reptiles and persecution and anti-conservation attitudes. Sociodemographic variables were also added. The results of the model suggest that the presence of folklore and negative values clearly predicts persecution and anti-conservation attitudes towards amphibians and reptiles. Also, the existence of folklore varies sociodemographically, but negative values concerning these animals are widespread in the population. With the use of structural equation models, this work is a contribution to the study of how certain ideas and values can directly influence human attitudes towards herpetofauna and how they can be a serious conservation issue.

  1. The epidemiology of human papillomavirus in HIV-negative and HIV-infected men who have sex with men

    NARCIS (Netherlands)

    Mooij, S.H.

    2015-01-01

    This thesis studied the epidemiology and seroepidemiology of human papillomavirus (HPV) among HIV-negative and HIV-infected men who have sex with men (MSM) in Amsterdam, the Netherlands. Anal, penile, and oral HPV prevalence and incidence were high, in particular among HIV-infected MSM. Clearance of

  2. High-Grade Squamous Intraepithelial Lesion Cytology With Negative High-Risk Human Papillomavirus Tests Rarely Diagnoses Endometrial Cancer.

    Science.gov (United States)

    Pretorius, Robert G; Peterson, Patricia

    2015-07-01

    We hypothesized that women with cervical cytologic results of high-grade squamous intraepithelial lesion (HSIL) and negative high-risk human papillomavirus (HR-HPV) test results would have a high risk of having endometrial cancer and would benefit from routine endometrial biopsy. Reports of women with cytologic results of HSIL and negative HR-HPV test results were found in an electronic colposcopy database; their charts were reviewed. Rates of endometrial cancer for cytologic results of HSIL and negative HR-HPV test results were compared to a historical series for cytologic results of HSIL with positive HR-HPV and cytologic results of atypical glandular cells (AGCs) and negative HR-HPV test results. Between August 10, 1998, and April 20, 2013, 56 women were evaluated in our colposcopy clinics for cytologic results of HSIL and negative HR-HPV test results; of these 56 women, 1 (1.8%) was diagnosed with endometrial cancer. No endometrial cancer was diagnosed during the follow-up (median = 63 mo) after colposcopy. The risk for endometrial cancer with cytologic results of HSIL and negative HR-HPV test results (1.8%, 1/56) did not differ from that of a historical series from 2007 to 2009 from the same colposcopy clinic in 223 women with cytologic results of HSIL and positive HR-HPV test results (0.0%, 0/223; p = .2) and was lower than the risk for endometrial cancer from the historical series from 2007 to 2009 in women with cytologic results of AGC and negative HR-HPV test results (14.4%, 4/27; p = .04). Women with cytologic results of HSIL and negative HR-HPV test results are more like those with cytologic results of HSIL and positive HR-HPV test results than those with cytologic results of AGC and negative HR-HPV test results and would unlikely to benefit from routine endometrial biopsy at the time of colposcopy.

  3. A negative cooperativity mechanism of human CYP2E1 inferred from molecular dynamics simulations and free energy calculations.

    Science.gov (United States)

    Li, Jue; Wei, Dong-Qing; Wang, Jing-Fang; Li, Yi-Xue

    2011-12-27

    Human cytochrome P450 2E1 (CYP2E1) participates in the metabolism of over 2% of all the oral drugs. A hallmark peculiar feature of this enzyme is that it exhibits a pronounced negative cooperativity in substrate binding. However the mechanism by which the negative cooperativity occurs is unclear. Here, we performed molecular dynamics simulations and free energy calculations on human CYP2E1 to examine the structural differences between the substrate-free and the enzymes with one and two aniline molecules bound. Our results indicate that although the effector substrate does not bind in the active site cavity, it still can directly interact with the active site residues of human CYP2E1. The interaction of the effector substrate with the active site leads to a reorientation of active site residues, which thereby weakens the interactions of the active substrate with this site. We also identify a conserved residue T303 that plays a crucial role in the negative cooperative binding on the short-range effects. This residue is a key factor in the positioning of substrates and in proton delivery to the active site. Additionally, a long-range effect of the effector substrate is identified in which F478 is proposed to play a key role. As located in the interface between the active and effector sites, this residue structurally links the active and effector sites and is found to play a significant role in affecting substrate access and ligand positioning within the active site. In the negative cooperative binding, this residue can decrease the interactions of the active substrate with the active site by π-π stacking which then lowers the hydroxylation activity for the active substrate. These findings are in agreement with previous experimental observations and thus provide detailed atomistic insight into the poorly understood mechanism of the negative cooperativity in human CYP2E1.

  4. Non-negative Tensor Factorization with missing data for the modeling of gene expressions in the Human Brain

    DEFF Research Database (Denmark)

    Nielsen, Søren Føns Vind; Mørup, Morten

    2014-01-01

    Non-negative Tensor Factorization (NTF) has become a prominent tool for analyzing high dimensional multi-way structured data. In this paper we set out to analyze gene expression across brain regions in multiple subjects based on data from the Allen Human Brain Atlas [1] with more than 40 % data...... from all subjects the model based predictions are useful. When analyzing the structure of the components derived for one of the best predicting model orders the components identified in general constitute localized regions of the brain. Non-negative tensor factorization based on marginalization thus...... missing in our problem. Our analysis is based on the non-negativity constrained Canonical Polyadic (CP) decomposition where we handle the missing data using marginalization considering three prominent alternating least squares procedures; multiplicative updates, column-wise, and row-wise updating...

  5. Increase in vagal activity during hypotensive lower-body negative pressure in humans

    DEFF Research Database (Denmark)

    Sander-Jensen, K; Mehlsen, J; Stadeager, C

    1988-01-01

    Progressive central hypovolemia is characterized by a normotensive, tachycardic stage followed by a reversible, hypotensive stage with slowing of the heart rate (HR). We investigated circulatory changes and arterial hormone concentrations in response to lower-body negative pressure (LBNP) in six...

  6. Atrial distension, arterial pulsation, and vasopressin release during negative pressure breathing in humans

    DEFF Research Database (Denmark)

    Pump, B; Damgaard, M; Gabrielsen, A

    2001-01-01

    During an antiorthostatic posture change, left atrial (LA) diameter and arterial pulse pressure (PP) increase, and plasma arginine vasopressin (AVP) is suppressed. By comparing the effects of a 15-min posture change from seated to supine with those of 15-min seated negative pressure breathing in ...

  7. Sensitivity of Human Choice to Manipulations of Parameters of Positive and Negative Sound Reinforcement

    Science.gov (United States)

    Lambert, Joseph M.

    2013-01-01

    The purpose of this study was to determine whether altering parameters of positive and negative reinforcement in identical ways could influence behavior maintained by each in different ways. Three undergraduate students participated in a series of assessments designed to identify preferred and aversive sounds with similar reinforcing values.…

  8. Human handedness in interactive situations: Negative perceptual frequency effects can be reversed!

    Science.gov (United States)

    Schorer, Jörg; Loffing, Florian; Hagemann, Norbert; Baker, Joseph

    2012-01-01

    Left-handed performers seem to enjoy an advantage in interactive sports. Researchers suggest this is predominantly due to the relative scarcity of left-handers compared with right-handers. Such negative frequency-dependent advantages are likely to appear in inefficient game-play behaviour against left-handed opponents such as reduced ability to correctly anticipate left-handers' action intentions. We used a pre-post retention design to test whether such negative frequency-dependent perceptual effects can be reversed via effective training. In a video-based test, 30 handball novices anticipated the shot outcome of temporally occluded handball penalties thrown by right- and left-handed players. Between the pre- and post-tests, participants underwent a perceptual training programme to improve prediction accuracy, followed by an unfilled retention test one week later. Participants were divided into two hand-specific training groups (i.e. only right- or left-handed shots were presented during training) and a mixed group (i.e. both right- and left-handed shots were presented). Our results support the negative frequency-dependent advantage hypothesis, as hand-specific perceptual training led to side-specific improvement of anticipation skills. Similarly, findings provide experimental evidence to support the contention that negatively frequency-dependent selection mechanisms contributed to the maintenance of the handedness polymorphism.

  9. The Effects of Different Drawing Materials on Children's Drawings of Positive and Negative Human Figures

    Science.gov (United States)

    Burkitt, Esther; Barrett, Martyn

    2011-01-01

    Children tend to use certain drawing strategies differentially when asked to draw topics with positive and negative emotional characterisations. These effects have however only been established when children are asked to use standard drawing materials. The present study was designed to investigate whether the above pattern of children's response…

  10. Can we regrow a human arm? A negative perspective from an upper-limb surgeon.

    Science.gov (United States)

    Merolli, Antonio

    2013-11-01

    If we would like to devote time and money to the task of regrowing a human arm, we should feel free to do it, in principle. However, if we recognize a purpose in biomedical research, we must scrutinize this task in the light of a possible clinical application. We will then discover that regrowing a human arm is not only likely to be not possible, but also not required in the clinic. Bionic arms and better reconstructive surgery already provide a different, simpler and easier solution to the loss of a human arm, and should be promoted. Probably, ‘‘can we regrow a human arm?’’ is not the right question. Instead, we should ask, ‘‘can we restore the function of a lost human arm?’’.

  11. Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer

    OpenAIRE

    Boér K

    2016-01-01

    Katalin Boér Department of Medical Oncology, Szent Margit Hospital, Budapest, Hungary Abstract: Breast cancer is a heterogeneous disease with multiple subgroups based on clinical and molecular characteristics. For the largest subgroup of breast cancers, hormone receptor-positive/human epidermal growth factor 2 (HER2)-negative tumors, hormone treatment is the mainstay of therapy and is likely to result in significant improvement in disease outcomes. However, some of these cancers ...

  12. Putative Biomarkers and Targets of Estrogen Receptor Negative Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Stephen W. Byers

    2011-07-01

    Full Text Available Breast cancer is a progressive and potentially fatal disease that affects women of all ages. Like all progressive diseases, early and reliable diagnosis is the key for successful treatment and annihilation. Biomarkers serve as indicators of pathological, physiological, or pharmacological processes. Her2/neu, CA15.3, estrogen receptor (ER, progesterone receptor (PR, and cytokeratins are biomarkers that have been approved by the Food and Drug Administration for disease diagnosis, prognosis, and therapy selection. The structural and functional complexity of protein biomarkers and the heterogeneity of the breast cancer pathology present challenges to the scientific community. Here we review estrogen receptor-related putative breast cancer biomarkers, including those of putative breast cancer stem cells, a minor population of estrogen receptor negative tumor cells that retain the stem cell property of self renewal. We also review a few promising cytoskeleton targets for ER alpha negative breast cancer.

  13. Design of miniaturized double-negative material for specific absorption rate reduction in human head.

    Directory of Open Access Journals (Sweden)

    Mohammad Rashed Iqbal Faruque

    Full Text Available In this study, a double-negative triangular metamaterial (TMM structure, which exhibits a resounding electric response at microwave frequency, was developed by etching two concentric triangular rings of conducting materials. A finite-difference time-domain method in conjunction with the lossy-Drude model was used in this study. Simulations were performed using the CST Microwave Studio. The specific absorption rate (SAR reduction technique is discussed, and the effects of the position of attachment, the distance, and the size of the metamaterials on the SAR reduction are explored. The performance of the double-negative TMMs in cellular phones was also measured in the cheek and the tilted positions using the COMOSAR system. The TMMs achieved a 52.28% reduction for the 10 g SAR. These results provide a guideline to determine the triangular design of metamaterials with the maximum SAR reducing effect for a mobile phone.

  14. Sex ratio at birth and mortality rates are negatively related in humans.

    Directory of Open Access Journals (Sweden)

    Madhukar Shivajirao Dama

    Full Text Available Evolutionary theory posits that resource availability and parental investment ability could signal offspring sex selection, in order to maximize reproductive returns. Non-human studies have provided evidence for this phenomenon, and maternal condition around the time of conception has been identified as most important factor that influence offspring sex selection. However, studies on humans have reported inconsistent results, mostly due to use of disparate measures as indicators of maternal condition. In the present study, the cross-cultural differences in human natal sex ratio were analyzed with respect to indirect measures of condition namely, life expectancy and mortality rate. Multiple regression modeling suggested that mortality rates have distinct predictive power independent of cross-cultural differences in fertility, wealth and latitude that were earlier shown to predict sex ratio at birth. These findings suggest that sex ratio variation in humans may relate to differences in parental and environmental conditions.

  15. Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy

    OpenAIRE

    Feng, Tingting; Cao, Wei; Shen, Wanxiang; Zhang, Liang; Gu, Xinsheng; Guo, Yang; Tsai, Hsiang-i; Liu, Xuewen; Li, Jian; Zhang, Jingxuan; Li, Shan; Wu, Fuyun; Liu, Ying

    2016-01-01

    Triple-negative breast cancers (TNBCs) are the most aggressive and hard-to-treat breast tumors with poor prognosis, and exploration for novel therapeutic drugs is impending. Arctigenin (Atn), a bioactive lignan isolated from seeds of Arctium lappa L, has been reported to inhibit many cancer types; however, the effect of Atn on TNBC remains unclear. In this study, we demonstrated that Atn decreased proliferation, and induced apoptosis in TNBC cells. Furthermore, we explored the underlying mech...

  16. Sex Ratio at Birth and Mortality Rates Are Negatively Related in Humans

    OpenAIRE

    Madhukar Shivajirao Dama

    2011-01-01

    Evolutionary theory posits that resource availability and parental investment ability could signal offspring sex selection, in order to maximize reproductive returns. Non-human studies have provided evidence for this phenomenon, and maternal condition around the time of conception has been identified as most important factor that influence offspring sex selection. However, studies on humans have reported inconsistent results, mostly due to use of disparate measures as indicators of maternal c...

  17. Coagulase-Negative Staphylococci in Human Milk From Mothers of Preterm Compared With Term Neonates.

    Science.gov (United States)

    Soeorg, Hiie; Metsvaht, Tuuli; Eelmäe, Imbi; Metsvaht, Hanna Kadri; Treumuth, Sirli; Merila, Mirjam; Ilmoja, Mari-Liis; Lutsar, Irja

    2017-05-01

    Human milk is the preferred nutrition for neonates and a source of bacteria. Research aim: The authors aimed to characterize the molecular epidemiology and genetic content of staphylococci in the human milk of mothers of preterm and term neonates. Staphylococci were isolated once per week in the 1st month postpartum from the human milk of mothers of 20 healthy term and 49 preterm neonates hospitalized in the neonatal intensive care unit. Multilocus variable-number tandem-repeats analysis and multilocus sequence typing were used. The presence of the mecA gene, icaA gene of the ica-operon, IS 256, and ACME genetic elements was determined by PCR. The human milk of mothers of preterm compared with term neonates had higher counts of staphylococci but lower species diversity. The human milk of mothers of preterm compared with term neonates more often contained Staphylococcus epidermidis mecA (32.7% vs. 2.6%), icaA (18.8% vs. 6%), IS 256 (7.9% vs. 0.9%), and ACME (15.4% vs. 5.1%), as well as Staphylococcus haemolyticus mecA (90.5% vs. 10%) and IS 256 (61.9% vs. 10%). The overall distribution of multilocus variable-number tandem-repeats analysis (MLVA) types and sequence types was similar between the human milk of mothers of preterm and term neonates, but a few mecA-IS 256-positive MLVA types colonized only mothers of preterm neonates. Maternal hospitalization within 1 month postpartum and the use of an arterial catheter or antibacterial treatment in the neonate increased the odds of harboring mecA-positive staphylococci in human milk. Limiting exposure of mothers of preterm neonates to the hospital could prevent human milk colonization with more pathogenic staphylococci.

  18. Associations Between Exposure to and Expression of Negative Opinions About Human Papillomavirus Vaccines on Social Media: An Observational Study.

    Science.gov (United States)

    Dunn, Adam G; Leask, Julie; Zhou, Xujuan; Mandl, Kenneth D; Coiera, Enrico

    2015-06-10

    Groups and individuals that seek to negatively influence public opinion about the safety and value of vaccination are active in online and social media and may influence decision making within some communities. We sought to measure whether exposure to negative opinions about human papillomavirus (HPV) vaccines in Twitter communities is associated with the subsequent expression of negative opinions by explicitly measuring potential information exposure over the social structure of Twitter communities. We hypothesized that prior exposure to opinions rejecting the safety or value of HPV vaccines would be associated with an increased risk of posting similar opinions and tested this hypothesis by analyzing temporal sequences of messages posted on Twitter (tweets). The study design was a retrospective analysis of tweets related to HPV vaccines and the social connections between users. Between October 2013 and April 2014, we collected 83,551 English-language tweets that included terms related to HPV vaccines and the 957,865 social connections among 30,621 users posting or reposting the tweets. Tweets were classified as expressing negative or neutral/positive opinions using a machine learning classifier previously trained on a manually labeled sample. During the 6-month period, 25.13% (20,994/83,551) of tweets were classified as negative; among the 30,621 users that tweeted about HPV vaccines, 9046 (29.54%) were exposed to a majority of negative tweets. The likelihood of a user posting a negative tweet after exposure to a majority of negative opinions was 37.78% (2780/7361) compared to 10.92% (1234/11,296) for users who were exposed to a majority of positive and neutral tweets corresponding to a relative risk of 3.46 (95% CI 3.25-3.67, PHPV vaccines. We found that among users that tweeted about HPV vaccines, those who were more often exposed to negative opinions were more likely to subsequently post negative opinions. Although this research may be useful for identifying

  19. Oral Human Papillomavirus Infection and Oral Lesions in HIV-Positive and HIV-Negative Dental Patients.

    Science.gov (United States)

    Muller, Katia; Kazimiroff, Julie; Fatahzadeh, Mahnaz; Smith, Richard V; Wiltz, Mauricio; Polanco, Jacqueline; Grossberg, Robert M; Belbin, Thomas J; Strickler, Howard D; Burk, Robert D; Schlecht, Nicolas F

    2015-09-01

    We evaluated the risk factors associated with oral human papillomavirus (HPV) infection and oral lesions in 161 human immunodeficiency virus (HIV)-positive patients and 128 HIV-negative patients presenting for oral examination at 2 urban healthcare centers. Patients were interviewed on risk factors and provided oral-rinse samples for HPV DNA typing by polymerase chain reaction. Statistical associations were assessed by logistic regression. Oral HPV was prevalent in 32% and 16% of HIV-positive patients and HIV-negative patients, respectively, including high-risk HPV type 16 (8% and 2%, respectively; P = .049) and uncommon HPV types 32/42 (6% and 5%, respectively; P = .715). Among HIV-negative patients, significant risk factors for oral HPV included multiple sex partners (≥21 vs ≤5; odds ratio [OR], 9.1; 95% confidence interval [CI], 1.7-49.3), heavy tobacco smoking (>20 pack-years vs none; OR, 9.2; 95% CI, 1.4-59.4), and marijuana use (OR, 4.0; 95% CI, 1.3-12.4). Among HIV-positive patients, lower CD4(+) T-cell count only was associated with oral HPV detection (≤200 vs ≥500 cells/mm(3); OR, 4.5; 95% CI, 1.3-15.5). Detection of high-risk HPV was also associated with concurrent detection of potentially cancerous oral lesions among HIV-negative patients but not among HIV-positive patients. The observed risk factor associations with oral HPV in HIV-negative patients are consistent with sexual transmission and local immunity, whereas in HIV-positive patients, oral HPV detection is strongly associated with low CD4(+) T-cell counts. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Positive and negative elements modulate the promoter of the human liver-specific alpha2-HS-glycoprotein gene.

    Science.gov (United States)

    Banine, F; Gangneux, C; Mercier, L; Le Cam, A; Salier, J P

    2000-02-01

    The human alpha2-HS-glycoprotein (AHSG) and the 63-kDa rat phosphoprotein (pp63) are homologous plasma proteins that belong to the fetuin family. AHSG and pp63 are involved in important functions such as inhibition of insulin receptor tyrosine kinase activity, inhibition of protease activities, and regulation of calcium metabolism and osteogenesis. Studies of the AHSG proximal promoter performed in vitro in rat and human cells indicate that several NF-1 and C/EBP binding sites exert a positive effect on its transcriptional activity. However, until now, no distal elements have been examined in this gene, in either species. We report that the human AHSG gene promoter acts in a liver-specific manner and is further controlled by three distal, 5'-flanking elements. The negative elements III and I are, respectively, located 5' and 3' of the positive element II. All three elements require the natural context of the human AHSG gene to fully exert their negative or positive effect. Element I harbours a single binding site for NF-1. This nuclear factor thus appears to be able to up- or downregulate the AHSG gene depending on the site it binds to. Elements I, II and possibly III are absent in the rodent Ahsg gene encoding pp63.

  1. Progesterone Negatively Regulates BCRP in Progesterone Receptor-Positive Human Breast Cancer Cells

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    Xiaojuan Wu

    2013-08-01

    Full Text Available Background/Aims: Breast cancer resistance protein (BCRP plays a crucial role in multidrug resistance (MDR. Previous studies have shown that steroid hormones, like progesterone (PROG, regulate BCRP expression. The presence of a progesterone response element (PRE in the BCRP promoter, suggests that PROG may regulate transcription of BCRP. Methods: To investigate the role of PROG in the regulation of BCRP expression, two constructs encoding full-length BCRP driven by either an endogenous PRE promoter or a constitutive CMV promoter, were transfected into T47D cells that express the progesterone receptor (PR or into PR-negative MDA-MB-231 cells. Results: After treatment with PROG, qPCR and Western blotting analyses indicated that BCRP mRNA and BCRP protein levels were significantly reduced in a dose-dependent manner in PR-positive cells, but PROG had no significant effect on BCRP levels in the PR-negative cells. The effect observed in PR-positive cells was reversed by co-treatment with RU-486, a specific PROG inhibitor. Cytometric analysis confirmed that BCRP-mediated drug efflux was inhibited and chemosensitivity to mitoxantrone was markedly increased by PROG treatment. Conclusion: These results suggest that PROG reverses BCRP-mediated MDR by down-regulating BCRP expression in breast cancer cells by affecting transcription from the PRE-containing BCRP promoter. Our studies suggest that breast cancer patients with BCRP-mediated MDR may be successfully treated with PROG.

  2. The effects of instructions on the sensitivity of negatively reinforced human behavior to extinction.

    Science.gov (United States)

    Alessandri, Jérôme; Cançado, Carlos R X

    2017-03-01

    The effects of instructions on the sensitivity of negatively reinforced (escape) behavior to extinction were studied. Initially, responding produced timeouts from pressing a force cell on a variable-ratio (VR) schedule, which was then discontinued (extinction). Based on extinction data, participants were distributed into two groups. Participants in the Persistence Group (for which response rates were low in extinction) were instructed that the experimenter expected them to continue responding in extinction after a second exposure to the VR schedule. Participants in the Extinction group (for which response rates were high in extinction) were instructed that the experimenter expected them to stop responding in extinction. Relative to the condition in which instructions were absent, extinction-response rates increased and decreased, respectively, for participants in the Persistence and Extinction groups. These results replicate and extend to negatively reinforced responding previous findings that showed behavioral control by instructions formulated as explicit experimenter demands or expectations. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. A Multi-Region Model of Economic Growth with Human Capital and Negative Externalities in Innovation

    NARCIS (Netherlands)

    Batabyal, A.; Nijkamp, P.

    2013-01-01

    We use a multi-region model and provide the first theoretical analysis of the effects of human capital use and a particular kind of innovative activity on economic growth. In each of the N heterogeneous regions in our model, consumers have constant relative risk aversion preferences, there are

  4. Laminar imaging of positive and negative BOLD in human visual cortex at 7T

    NARCIS (Netherlands)

    Fracasso, Alessio; Luijten, Peter R; Dumoulin, Serge O; Petridou, Natalia

    2017-01-01

    Deciphering the direction of information flow is critical to understand the brain. Data from non-human primate histology shows that connections between lower to higher areas (e.g. retina→V1), and between higher to lower areas (e.g. V1←V2) can be dissociated based upon the distribution of afferent

  5. Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy.

    Science.gov (United States)

    Feng, Tingting; Cao, Wei; Shen, Wanxiang; Zhang, Liang; Gu, Xinsheng; Guo, Yang; Tsai, Hsiang-I; Liu, Xuewen; Li, Jian; Zhang, Jingxuan; Li, Shan; Wu, Fuyun; Liu, Ying

    2017-01-03

    Triple-negative breast cancers (TNBCs) are the most aggressive and hard-to-treat breast tumors with poor prognosis, and exploration for novel therapeutic drugs is impending. Arctigenin (Atn), a bioactive lignan isolated from seeds of Arctium lappa L, has been reported to inhibit many cancer types; however, the effect of Atn on TNBC remains unclear. In this study, we demonstrated that Atn decreased proliferation, and induced apoptosis in TNBC cells. Furthermore, we explored the underlying mechanism of Atn inhibition on TNBC cells. Computational docking and affinity assay showed that Atn bound to the SH2 domain of STAT3. Atn inhibited STAT3 binding to genomic DNA by disrupting hydrogen bond linking between DNA and STAT3. In addition, Atn augmented Taxotere®-induced TNBC cell cytotoxicity. TNBC xenograft tests also confirmed the antitumor effect of Atn in vivo. These characteristics render Atn as a promising candidate drug for further development and for designing new effective STAT3 inhibitors.

  6. Categorical dimensions of human odor descriptor space revealed by non-negative matrix factorization.

    Directory of Open Access Journals (Sweden)

    Jason B Castro

    Full Text Available In contrast to most other sensory modalities, the basic perceptual dimensions of olfaction remain unclear. Here, we use non-negative matrix factorization (NMF--a dimensionality reduction technique--to uncover structure in a panel of odor profiles, with each odor defined as a point in multi-dimensional descriptor space. The properties of NMF are favorable for the analysis of such lexical and perceptual data, and lead to a high-dimensional account of odor space. We further provide evidence that odor dimensions apply categorically. That is, odor space is not occupied homogenously, but rather in a discrete and intrinsically clustered manner. We discuss the potential implications of these results for the neural coding of odors, as well as for developing classifiers on larger datasets that may be useful for predicting perceptual qualities from chemical structures.

  7. Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Dávila-Román, Victor G; Ostlund, Richard E

    2017-12-01

    Epidemiological studies strongly suggest that lipid factors independent of low-density lipoprotein cholesterol contribute significantly to cardiovascular disease risk. Because circulating lipoproteins comprise only a small fraction of total body cholesterol, the mobilization and excretion of cholesterol from plasma and tissue pools may be an important determinant of cardiovascular disease risk. Our hypothesis is that fecal excretion of endogenous cholesterol is protective against atherosclerosis. Cholesterol metabolism and carotid intima-media thickness were quantitated in 86 nondiabetic adults. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 solubilized in a lipid emulsion and dietary cholesterol by cholesterol-d 5 and the nonabsorbable stool marker sitostanol-d 4 . Plasma and stool samples were collected while subjects consumed a cholesterol- and phytosterol-controlled metabolic kitchen diet and were analyzed by mass spectrometry. Carotid intima-media thickness was negatively correlated with fecal excretion of endogenous cholesterol ( r =-0.426; P cholesterol ( r =-0.472; P ≤0.0001), and daily percent excretion of cholesterol from the rapidly mixing cholesterol pool ( r =-0.343; P =0.0012) and was positively correlated with percent cholesterol absorption ( r =+0.279; P =0.0092). In a linear regression model controlling for age, sex, systolic blood pressure, hemoglobin A1c, low-density lipoprotein, high-density lipoprotein cholesterol, and statin drug use, fecal excretion of endogenous cholesterol remained significant ( P =0.0008). Excretion of endogenous cholesterol is strongly, independently, and negatively associated with carotid intima-media thickness. The reverse cholesterol transport pathway comprising the intestine and the rapidly mixing plasma, and tissue cholesterol pool could be an unrecognized determinant of cardiovascular disease risk not reflected in circulating lipoproteins. Further work is needed to relate measures of

  8. Negative Impacts of Human Land Use on Dung Beetle Functional Diversity

    OpenAIRE

    Barragán, Felipe; Moreno, Claudia E.; Escobar, Federico; Halffter, Gonzalo; Navarrete, Dario

    2011-01-01

    The loss of biodiversity caused by human activity is assumed to alter ecosystem functioning. However our understanding of the magnitude of the effect of these changes on functional diversity and their impact on the dynamics of ecological processes is still limited. We analyzed the functional diversity of copro-necrophagous beetles under different conditions of land use in three Mexican biosphere reserves. In Montes Azules pastures, forest fragments and continuous rainforest were analyzed, in ...

  9. Facing negative reactions to sexuality education through a Multicultural Human Rights framework.

    Science.gov (United States)

    Paiva, Vera; Silva, Valeria N

    2015-11-01

    Sexuality education, its protocols and planning are contingent on an ever-changing political environment that characterizes the field of sexuality in most countries. In Brazil, human rights perspectives shaped the country's response to the AIDS epidemic, and indirectly influenced the public acceptability of sexuality education in schools. Since 2011, however, as multiple fundamentalist movements emerged in the region, leading to recurrent waves of backlashes in all matters related to sexuality, both health and educational policies have begun to crawl backwards. This article explores human rights-based approaches to health, focusing on a multicultural rights-based framework and on productive approaches to broadening the dialogue about sustained consent to sexuality education. Multicultural human rights (MHR) approaches are dialogical in two domains: the communication process that guarantees consent and community agreements and the constructionist psychosocial-educational methodologies. In its continuous process of consent, the MHR approach allowed for distinct values translation and diffused the resistance to sexuality education in the participant schools/cities, successfully sustaining notions of equality and protection of the right to a comprehensive sexuality education that does not break group solidarity and guarantees acceptability of differences. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Fishery-independent data reveal negative effect of human population density on Caribbean predatory fish communities.

    Directory of Open Access Journals (Sweden)

    Christopher D Stallings

    Full Text Available BACKGROUND: Understanding the current status of predatory fish communities, and the effects fishing has on them, is vitally important information for management. However, data are often insufficient at region-wide scales to assess the effects of extraction in coral reef ecosystems of developing nations. METHODOLOGY/PRINCIPAL FINDINGS: Here, I overcome this difficulty by using a publicly accessible, fisheries-independent database to provide a broad scale, comprehensive analysis of human impacts on predatory reef fish communities across the greater Caribbean region. Specifically, this study analyzed presence and diversity of predatory reef fishes over a gradient of human population density. Across the region, as human population density increases, presence of large-bodied fishes declines, and fish communities become dominated by a few smaller-bodied species. CONCLUSIONS/SIGNIFICANCE: Complete disappearance of several large-bodied fishes indicates ecological and local extinctions have occurred in some densely populated areas. These findings fill a fundamentally important gap in our knowledge of the ecosystem effects of artisanal fisheries in developing nations, and provide support for multiple approaches to data collection where they are commonly unavailable.

  11. Fishery-Independent Data Reveal Negative Effect of Human Population Density on Caribbean Predatory Fish Communities

    Science.gov (United States)

    Stallings, Christopher D.

    2009-01-01

    Background Understanding the current status of predatory fish communities, and the effects fishing has on them, is vitally important information for management. However, data are often insufficient at region-wide scales to assess the effects of extraction in coral reef ecosystems of developing nations. Methodology/Principal Findings Here, I overcome this difficulty by using a publicly accessible, fisheries-independent database to provide a broad scale, comprehensive analysis of human impacts on predatory reef fish communities across the greater Caribbean region. Specifically, this study analyzed presence and diversity of predatory reef fishes over a gradient of human population density. Across the region, as human population density increases, presence of large-bodied fishes declines, and fish communities become dominated by a few smaller-bodied species. Conclusions/Significance Complete disappearance of several large-bodied fishes indicates ecological and local extinctions have occurred in some densely populated areas. These findings fill a fundamentally important gap in our knowledge of the ecosystem effects of artisanal fisheries in developing nations, and provide support for multiple approaches to data collection where they are commonly unavailable. PMID:19421312

  12. Evidence for phenotypic plasticity in aggressive triple-negative breast cancer: human biology is recapitulated by a novel model system.

    Directory of Open Access Journals (Sweden)

    Nicholas C D'Amato

    Full Text Available Breast cancers with a basal-like gene signature are primarily triple-negative, frequently metastatic, and carry a poor prognosis. Basal-like breast cancers are enriched for markers of breast cancer stem cells as well as markers of epithelial-mesenchymal transition (EMT. While EMT is generally thought to be important in the process of metastasis, in vivo evidence of EMT in human disease remains rare. Here we report a novel model of human triple-negative breast cancer, the DKAT cell line, which was isolated from an aggressive, treatment-resistant triple-negative breast cancer that demonstrated morphological and biochemical evidence suggestive of phenotypic plasticity in the patient. The DKAT cell line displays a basal-like phenotype in vitro when cultured in serum-free media, and undergoes phenotypic changes consistent with EMT/MET in response to serum-containing media, a unique property among the breast cancer cell lines we tested. This EMT is marked by increased expression of the transcription factor Zeb1, and Zeb1 is required for the enhanced migratory ability of DKAT cells in the mesenchymal state. DKAT cells also express progenitor-cell markers, and single DKAT cells are able to generate tumorspheres containing both epithelial and mesenchymal cell types. In vivo, as few as ten DKAT cells are capable of forming xenograft tumors which display a range of epithelial and mesenchymal phenotypes. The DKAT model provides a novel model to study the molecular mechanisms regulating phenotypic plasticity and the aggressive biology of triple-negative breast cancers.

  13. Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda.

    Science.gov (United States)

    Wawer, Maria J; Tobian, Aaron A R; Kigozi, Godfrey; Kong, Xiangrong; Gravitt, Patti E; Serwadda, David; Nalugoda, Fred; Makumbi, Frederick; Ssempiija, Victor; Sewankambo, Nelson; Watya, Stephen; Eaton, Kevin P; Oliver, Amy E; Chen, Michael Z; Reynolds, Steven J; Quinn, Thomas C; Gray, Ronald H

    2011-01-15

    Randomised trials show that male circumcision reduces the prevalence and incidence of high-risk human papillomavirus (HPV) infection in men. We assessed the efficacy of male circumcision to reduce prevalence and incidence of high-risk HPV in female partners of circumcised men. In two parallel but independent randomised controlled trials of male circumcision, we enrolled HIV-negative men and their female partners between 2003 and 2006, in Rakai, Uganda. With a computer-generated random number sequence in blocks of 20, men were assigned to undergo circumcision immediately (intervention) or after 24 months (control). HIV-uninfected female partners (648 of men from the intervention group, and 597 of men in the control group) were simultaneously enrolled and provided interview information and self-collected vaginal swabs at baseline, 12 months, and 24 months. Vaginal swabs were tested for high-risk HPV by Roche HPV Linear Array. Female HPV infection was a secondary endpoint of the trials, assessed as the prevalence of high-risk HPV infection 24 months after intervention and the incidence of new infections during the trial. Analysis was by intention-to-treat. An as-treated analysis was also done to account for study-group crossovers. The trials were registered, numbers NCT00425984 and NCT00124878. During the trial, 18 men in the control group underwent circumcision elsewhere, and 31 in the intervention group did not undergo circumcision. At 24-month follow-up, data were available for 544 women in the intervention group and 488 in the control group; 151 (27·8%) women in the intervention group and 189 (38·7%) in the control group had high-risk HPV infection (prevalence risk ratio=0·72, 95% CI 0·60-0·85, p=0·001). During the trial, incidence of high-risk HPV infection in women was lower in the intervention group than in the control group (20·7 infections vs 26·9 infections per 100 person-years; incidence rate ratio=0·77, 0·63-0·93, p=0·008). Our findings

  14. Male circumcision wound healing in human immunodeficiency virus (HIV)-negative and HIV-positive men in Rakai, Uganda.

    Science.gov (United States)

    Kigozi, Godfrey; Musoke, Richard; Kighoma, Nehemiah; Watya, Stephen; Serwadda, David; Nalugoda, Fred; Kiwanuka, Noah; Nkale, James; Wabwire-Mangen, Fred; Makumbi, Frederick; Sewankambo, Nelson K; Gray, Ronald H; Wawer, Maria J

    2014-01-01

    To assess completed wound healing after medical male circumcision (MMC) among human immunodeficiency virus (HIV)-negative and HIV-positive men with cluster of differentiation 4 (CD4) counts of HIV-positive men with low CD4 counts. In all, 262 HIV-negative and 177 HIV-positive consenting males aged ≥12 years accepted MMC using the dorsal slit procedure and were enrolled in the study. Socio-demographic and behavioural data and blood for HIV testing and CD4 counts were collected at baseline. Participants were followed weekly to collect information on resumption of sex, condom use and both self-reported and clinically assessed wound healing. The proportions healed among HIV-positive men were compared with HIV-negative men. Time to complete wound healing was assessed by Kaplan-Meier survival analysis. There were no statistically significant differences in the proportion of men healed by HIV status. At 4 weeks, the proportions healed were 85.9% in HIV-negative men, 77.4% in HIV-positive men with a CD4 count of ≥350 cells/mm(3) and 87.1% in HIV-positive men with a CD4 count of healing was 4 weeks and did not vary by HIV or CD4 status. All men had certified complete wound healing at 6 weeks after MMC. In all, 1.4% of HIV-positive men with a CD4 count of healing, compared with 8.5% among HIV-positive men with a CD4 count of ≥350 cells/mm(3) (P = 0.052) and 7.8% (P = 0.081) among HIV-negative men. Inclusion of HIV-positive men with low CD4 counts in MMC services is not deleterious to postoperative wound healing. © 2013 The Authors. BJU International © 2013 BJU International.

  15. Negatively cooperative binding properties of human cytochrome P450 2E1 with monocyclic substrates.

    Science.gov (United States)

    Ping, Jie; Wang, Ya-Jun; Wang, Jing-Fang; Li, Xuan; Li, Yi-Xue; Hao, Pei

    2012-09-01

    Human CYP2E1 accounts for almost 2% of total CYP enzymes in the liver cells, and plays a crucial role in the metabolism of small molecular weight compounds. This enzyme is associated with the nearly 6% metabolisms of the currently clinical drugs. However, it is found that CYP2E1 has a non-hyperbolic kinetic profile that can not be explained by the common Michaelis-Menten mechanism. Further studies show that the non-hyperbolic kinetic behaviors are associated with multiple substrate binding, which is also known as the cooperative binding properties. However, the detailed mechanism for the cooperative binding is not clear by now. In this paper, we summarized the experimental and theoretical studies on the cooperative binding mechanism. Based on the structural analysis, a second substrate binding site is confirmed in human CYP2E1, which is located neither in the region near Leu103, Leu210 and Phe478, nor far from the active site. Additionally, two important residues Thr303 and Phe478 are also identified to be the key factors in the cooperative binding on the short-range and long-range effects, respectively. The former plays a crucial role in the positioning of substrates and in proton delivery to the active site; the latter is located between the substrate access channel and the active site, and exhibits directly effects on substrate access or on substrate positioning in the active site. All these points can provide useful information for the cooperative binding in human CYP2E1, revealing the detailed mechanism for the non-hyperbolic kinetic behaviors.

  16. Neuronal plasticity after a human spinal cord injury: positive and negative effects.

    Science.gov (United States)

    Dietz, Volker

    2012-05-01

    In patients suffering an incomplete spinal cord injury (SCI) an improvement in walking function can be achieved by providing a functional training with an appropriate afferent input. In contrast, in immobilized incomplete and complete subjects a negative neuroplasticity leads to a neuronal dysfunction. After an SCI, neuronal centers below the level of lesion exhibit plasticity that either can be exploited by specific training paradigms or undergo a degradation of function due to the loss of appropriate input. Load- and hip-joint-related afferent inputs seem to be of crucial importance for the generation of a locomotor pattern and, consequently, the effectiveness of the locomotor training. In severely affected SCI subjects rehabilitation robots allow for a longer and more intensive training and can provide feedback information. Conversely, in severely affected chronic SCI individuals without functional training the locomotor activity in the leg muscles exhausts rapidly during assisted locomotion. This is accompanied by a shift from early to dominant late spinal reflex components. The exhaustion of locomotor activity is also observed in non-ambulatory patients with an incomplete SCI. It is assumed that in chronic SCI the patient's immobility results in a reduced input from supraspinal and peripheral sources and leads to a dominance of inhibitory drive within spinal neuronal circuitries underlying locomotor pattern and spinal reflex generation. A training with an enhancement of an appropriate proprioceptive input early after an SCI might serve as an intervention to prevent neuronal dysfunction. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Sustained negative BOLD response in human fMRI finger tapping task.

    Directory of Open Access Journals (Sweden)

    Yadong Liu

    Full Text Available In this work, we investigated the sustained negative blood oxygen level-dependent (BOLD response (sNBR using functional magnetic resonance imaging during a finger tapping task. We observed that the sNBR for this task was more extensive than has previously been reported. The cortical regions involved in sNBR are divided into the following three groups: frontal, somatosensory and occipital. By investigating the spatial structure, area, amplitude, and dynamics of the sNBR in comparison with those of its positive BOLD response (PBR counterpart, we made the following observations. First, among the three groups, the somatosensory group contained the greatest number of activated voxels and the fewest deactivated voxels. In addition, the amplitude of the sNBR in this group was the smallest among the three groups. Second, the onset and peak time of the sNBR are both larger than those of the PBR, whereas the falling edge time of the sNBR is less than that of the PBR. Third, the long distance between most sNBR foci and their corresponding PBR foci makes it unlikely that they share the same blood supply artery. Fourth, the couplings between the sNBR and its PBR counterpart are distinct among different regions and thus should be investigated separately. These findings imply that the origin of most sNBR foci in the finger-tapping task is much more likely to be neuronal activity suppression rather than "blood steal."

  18. Arctigenin inhibits STAT3 and exhibits anticancer potential in human triple-negative breast cancer therapy

    Science.gov (United States)

    Shen, Wanxiang; Zhang, Liang; Gu, Xinsheng; Guo, Yang; Tsai, Hsiang-i; Liu, Xuewen; Li, Jian; Zhang, Jingxuan; Li, Shan; Wu, Fuyun; Liu, Ying

    2017-01-01

    Triple-negative breast cancers (TNBCs) are the most aggressive and hard-to-treat breast tumors with poor prognosis, and exploration for novel therapeutic drugs is impending. Arctigenin (Atn), a bioactive lignan isolated from seeds of Arctium lappa L, has been reported to inhibit many cancer types; however, the effect of Atn on TNBC remains unclear. In this study, we demonstrated that Atn decreased proliferation, and induced apoptosis in TNBC cells. Furthermore, we explored the underlying mechanism of Atn inhibition on TNBC cells. Computational docking and affinity assay showed that Atn bound to the SH2 domain of STAT3. Atn inhibited STAT3 binding to genomic DNA by disrupting hydrogen bond linking between DNA and STAT3. In addition, Atn augmented Taxotere®-induced TNBC cell cytotoxicity. TNBC xenograft tests also confirmed the antitumor effect of Atn in vivo. These characteristics render Atn as a promising candidate drug for further development and for designing new effective STAT3 inhibitors. PMID:27861147

  19. Histological analysis of gamma delta T lymphocytes infiltrating human triple-negative breast carcinomas

    Directory of Open Access Journals (Sweden)

    Jose Villacorta Hidalgo

    2014-12-01

    Full Text Available Breast cancer is the leading cause of cancer death in women and the second most common cancer worldwide after lung cancer. The remarkable heterogeneity of breast cancers influences numerous diagnostic, therapeutic and prognostic factors. Triple-negative breast cancers (TNBCs lack expression of HER2 and the estrogen and progesterone receptors and often contain lymphocytic infiltrates. Most of TNBCs are invasive ductal carcinomas (IDCs with poor prognosis, whereas prognostically more favorable subtypes such as medullary breast carcinomas (MBCs are somewhat less frequent. Infiltrating T cells have been associated with an improved clinical outcome in TNBCs. The prognostic role of γδ T cells within CD3+ tumor-infiltrating T lymphocytes remains unclear. We analyzed 26 TNBCs, 14 IDCs and 12 MBCs, using immunohistochemistry for the quantity and patterns of γδ T-cell infitrates within the tumor microenvironment. In both types of TNBCs, we found higher numbers of γδ T cells in comparison with normal breast tissues and fibroadenomas. The numbers of infiltrating γδ T cells were higher in MBCs than in IDCs. γδ T cells in MBCs were frequently located in direct contact with tumor cells, within the tumor and at its invasive border. In contrast, most γδ T cells in IDCs were found in clusters within the tumor stroma. These findings could be associated with the fact that the patient’s prognosis in MBCs is better than that in IDCs. Further studies to characterize these γδ T cells at the molecular and functional level are in progress.

  20. Coagulation changes during lower body negative pressure and blood loss in humans.

    Science.gov (United States)

    van Helmond, Noud; Johnson, Blair D; Curry, Timothy B; Cap, Andrew P; Convertino, Victor A; Joyner, Michael J

    2015-11-01

    We tested the hypothesis that markers of coagulation activation are greater during lower body negative pressure (LBNP) than those obtained during blood loss (BL). We assessed coagulation using both standard clinical tests and thrombelastography (TEG) in 12 men who performed a LBNP and BL protocol in a randomized order. LBNP consisted of 5-min stages at 0, -15, -30, and -45 mmHg of suction. BL included 5 min at baseline and following three stages of 333 ml of blood removal (up to 1,000 ml total). Arterial blood draws were performed at baseline and after the last stage of each protocol. We found that LBNP to -45 mmHg is a greater central hypovolemic stimulus versus BL; therefore, the coagulation markers were plotted against central venous pressure (CVP) to obtain stimulus-response relationships using the linear regression line slopes for both protocols. Paired t-tests were used to determine whether the slopes of these regression lines fell on similar trajectories for each protocol. Mean regression line slopes for coagulation markers versus CVP fell on similar trajectories during both protocols, except for TEG α° angle (-0.42 ± 0.96 during LBNP vs. -2.41 ± 1.13°/mmHg during BL; P coagulation was accelerated as evidenced by shortened R-times (LBNP, 9.9 ± 2.4 to 6.2 ± 1.1; BL, 8.7 ± 1.3 to 6.4 ± 0.4 min; both P coagulation markers observed during BL. Copyright © 2015 the American Physiological Society.

  1. Higher prevalence of oral human papillomavirus infection in HIV-positive than HIV-negative Thai men and women.

    Science.gov (United States)

    Vacharotayangul, Piamkamon; Rungsiyanont, Sorasun; Lam-Ubol, Aroonwan; Pankam, Tippawan; Rodbamrung, Piyanee; Naorungroj, Supawadee; Phanuphak, Nittaya

    2015-12-01

    This study was designed to investigate the prevalence of oral human papillomavirus (HPV) infection among HIV-positive and HIV-negative Thai men and women. Participants including men who have sex with men (MSM) and heterosexual women were enrolled at the Thai Red Cross Anonymous Clinic in Bangkok. History taking and oral examination were performed by three independent dentists after calibration. HPV infection was evaluated from oral rinse with mouthwash collected at the time of examination. HPV typing was performed by PCR and nucleic acid hybridization to detect thirty-seven HPV DNA genotypes using Linear Array(®) HPV Genotyping Test (Roche Molecular System, Inc.). 244 subjects were enrolled in the study, consisted of 187 HIV-positive (51.9% women and 48.1% MSM) and 57 HIV-negative (21.0% women and 79.0% MSM) Thai subjects. The prevalence of oral HPV infection was 17.2% in HIV-positive subjects whereas only 5.3% of HIV-negative cases had HPV detected in their oral rinses (p=0.0346). Among HIV positive subjects, MSM had higher chance of having HPV infection than females (25% vs. 9.4%, p=0.0074). HIV-positive Thai MSM and women had higher prevalence of oral HPV infection than those without HIV. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Negative impact of endocrine-disrupting compounds on human reproductive health.

    Science.gov (United States)

    Balabanič, Damjan; Rupnik, Marjan; Klemenčič, Aleksandra Krivograd

    2011-01-01

    There is increasing concern about chemical pollutants that are able to mimic hormones, the so-called endocrine-disrupting compounds (EDCs), because of their structural similarity to endogenous hormones, their ability to interact with hormone transport proteins or because of their potential to disrupt hormone metabolic pathways. Thus, the effects of endogenous hormones can be mimicked or, in some cases, completely blocked. A substantial number of environmental pollutants, such as polychlorinated biphenyls, dioxins, polycyclic aromatic hydrocarbons, phthalates, bisphenol A, pesticides, alkylphenols and heavy metals (arsenic, cadmium, lead, mercury), have been shown to disrupt endocrine function. These compounds can cause reproductive problems by decreasing sperm count and quality, increasing the number of testicular germ cells and causing male breast cancer, cryptorchidism, hypospadias, miscarriages, endometriosis, impaired fertility, irregularities of the menstrual cycle, and infertility. Although EDCs may be released into the environment in different ways, the main sources is industrial waste water. The present paper critically reviews the current knowledge of the impact of EDCs on reproductive disorders in humans.

  3. Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

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    Hyunjung Choi

    Full Text Available The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH-smoothened (Smo signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

  4. Tyrosine agonists reverse the molecular defects associated with dominant-negative mutations in human peroxisome proliferator-activated receptor gamma.

    Science.gov (United States)

    Agostini, Maura; Gurnell, Mark; Savage, David B; Wood, Emily M; Smith, Aaron G; Rajanayagam, Odelia; Garnes, Keith T; Levinson, Sidney H; Xu, H Eric; Schwabe, John W R; Willson, Timothy M; O'Rahilly, Stephen; Chatterjee, V Krishna

    2004-04-01

    Loss-of-function mutations in the ligand-binding domain of human peroxisome proliferator-activated receptor gamma (PPARgamma) are associated with a novel syndrome characterized by partial lipodystrophy and severe insulin resistance. Here we have further characterized the properties of natural dominant-negative PPARgamma mutants (P467L, V290M) and evaluated the efficacy of putative natural ligands and synthetic thiazolidinedione (TZD) or tyrosine-based (TA) receptor agonists in rescuing mutant receptor function. A range of natural ligands failed to activate the PPARgamma mutants and their transcriptional responses to TZDs (e.g. pioglitazone, rosiglitazone) were markedly attenuated, whereas TAs (e.g. farglitazar) corrected defects in ligand binding and coactivator recruitment by the PPARgamma mutants, restoring transcriptional function comparable with wild-type receptor. Transcriptional silencing via recruitment of corepressor contributes to dominant-negative inhibition of wild type by the P467L and V290M mutants and the introduction of an artificial mutation (L318A) disrupting corepressor interaction abrogated their dominant-negative activity. More complete ligand-dependent corepressor release and reversal of dominant-negative inhibition was achieved with TA than TZD agonists. Modeling suggests a structural basis for these observations: both mutations destabilize helix 12 to favor receptor-corepressor interaction; conversely, farglitazar makes more extensive contacts than rosiglitazone within the ligand-binding pocket, to stabilize helix 12, facilitating corepressor release and transcriptional activation. Farglitazar was a more potent inducer of PPARgamma target gene (aP2) expression in peripheral blood mononuclear cells with the P467L mutation. Having shown that rosiglitazone is of variable and limited efficacy in these subjects, we suggest that TAs may represent a more rational therapeutic approach.

  5. [The negative psychology for the public in Zhejiang province during the epidemic of human H7N9 avian influenza].

    Science.gov (United States)

    Zhang, Renjie; Jiang, Tingting; Li, Na; Wang, Zhen; Liu, Biyao; Fang, Le; Zhang, Xinwei

    2015-12-01

    To evaluate the cognition and emotional response of the public in Zhejiang province during the epidemic of human H7N9 avian influenza and provide scientific support for group psychological intervention under public health emergency. 57 communities in 19 counties from Hangzhou, Jiaxing and Lishui district of Zhejiang province were selected as survey sites using stratified clustered sampling method from March, 2013 to April, 2014. 2 319 ordinary civilians were chosen using convenience sampling method and 390 individuals who had close contact history with H7N9 avian influenza patients, 109 family members of patients and 281 medical workers, were selected using census method. The inclusion criteria for subjects were: subjects aged over 10 years; could complete the questionnaire independently or with the help of the investigators. A total of 2 709 subjects were surveyed by avian influenza risk perception and response questionnaire, negative emotion questionnaire was also used to see their cognition and negative emotion related to the disease. Spearman correlation analysis was used to analyze the interrelationship between public risk perception, response and negative emotions. 95.10% (2 576)of the subjects have sensed the risk of epidemic and 91.00% (2 465) of the subjects have taken preventive measures in 2 709 subjects. The positive rate for depression, neurasthenia, fear, anxiety and hypochondriasis were 36.40% (986) , 37.21% (1 008) , 79.70% (2 159) , 33.41% (905) , 27.69% (750) respectively (χ(2)=1 935.89, Panalysis showed that the subjects' risk perception level was positively correlated with depression, neurasthenia, fear, and hypochondriasis, with the correlation coefficients 0.07, 0.07, 0.08, 0.04, respectively (Ppsychology health were risk factors of disease related negative emotions. The subject's risk perception and response level was positively related with depression, neurasthenia, fear and hypochondriasis.

  6. High-risk human papillomavirus viral load and persistence among heterosexual HIV-negative and HIV-positive men.

    Science.gov (United States)

    Grabowski, Mary K; Gray, Ronald H; Serwadda, David; Kigozi, Godfrey; Gravitt, Patti E; Nalugoda, Fred; Reynolds, Steven J; Wawer, Maria J; Watya, Stephen; Quinn, Thomas C; Tobian, Aaron A R

    2014-06-01

    High-risk human papillomavirus (HR-HPV) viral load is associated with HR-HPV transmission and HR-HPV persistence in women. It is unknown whether HR-HPV viral load is associated with persistence in HIV-negative or HIV-positive men. HR-HPV viral load and persistence were evaluated among 703 HIV-negative and 233 HIV-positive heterosexual men who participated in a male circumcision trial in Rakai, Uganda. Penile swabs were tested at baseline and 6, 12 and 24 months for HR-HPV using the Roche HPV Linear Array, which provides a semiquantitative measure of HPV shedding by hybridisation band intensity (graded: 1-4). Prevalence risk ratios (PRR) were used to estimate the association between HR-HPV viral load and persistent detection of HR-HPV. HR-HPV genotypes with high viral load (grade:3-4) at baseline were more likely to persist than HR-HPV genotypes with low viral load (grade: 1-2) among HIV-negative men (month 6: adjPRR=1.83, 95% CI 1.32 to 2.52; month 12: adjPRR=2.01, 95% CI 1.42 to 3.11), and HIV-positive men (month 6: adjPRR=1.33, 95% CI 1.06 to 1.67; month 12: adjPRR=1.73, 95% CI 1.18 to 2.54). Long-term persistence of HR-HPV was more frequent among HIV-positive men compared with HIV-negative men (month 24: adjPRR=2.27, 95% CI 1.47 to 3.51). Persistence of newly detected HR-HPV at the 6-month and 12-month visits with high viral load were also more likely to persist to 24 months than HR-HPV with low viral load among HIV-negative men (adjPRR=1.67, 95% CI 0.88 to 3.16). HR-HPV genotypes with high viral load are more likely to persist among HIV-negative and HIV-positive men, though persistence was more common among HIV-positive men overall. The results may explain the association between high HR-HPV viral load and HR-HPV transmission. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Negative impacts of human land use on dung beetle functional diversity.

    Science.gov (United States)

    Barragán, Felipe; Moreno, Claudia E; Escobar, Federico; Halffter, Gonzalo; Navarrete, Dario

    2011-03-23

    The loss of biodiversity caused by human activity is assumed to alter ecosystem functioning. However our understanding of the magnitude of the effect of these changes on functional diversity and their impact on the dynamics of ecological processes is still limited. We analyzed the functional diversity of copro-necrophagous beetles under different conditions of land use in three Mexican biosphere reserves. In Montes Azules pastures, forest fragments and continuous rainforest were analyzed, in Los Tuxtlas rainforest fragments of different sizes were analyzed and in Barranca de Metztitlán two types of xerophile scrub with different degrees of disturbance from grazing were analyzed. We assigned dung beetle species to functional groups based on food relocation, beetle size, daily activity period and food preferences, and as measures of functional diversity we used estimates based on multivariate methods. In Montes Azules functional richness was lower in the pastures than in continuous rainforest and rainforest fragments, but fragments and continuous forest include functionally redundant species. In small rainforest fragments (20 ha). Functional evenness and functional dispersion did not vary among habitat types or fragment size in these reserves. In contrast, in Metztitlán, functional richness and functional dispersion were different among the vegetation types, but differences were not related to the degree of disturbance by grazing. More redundant species were found in submontane than in crassicaule scrub. For the first time, a decrease in the functional diversity in communities of copro-necrophagous beetles resulting from changes in land use is documented, the potential implications for ecosystem functioning are discussed and a series of variables that could improve the evaluation of functional diversity for this biological group is proposed.

  8. Negative Impacts of Human Land Use on Dung Beetle Functional Diversity

    Science.gov (United States)

    Barragán, Felipe; Moreno, Claudia E.; Escobar, Federico; Halffter, Gonzalo; Navarrete, Dario

    2011-01-01

    The loss of biodiversity caused by human activity is assumed to alter ecosystem functioning. However our understanding of the magnitude of the effect of these changes on functional diversity and their impact on the dynamics of ecological processes is still limited. We analyzed the functional diversity of copro-necrophagous beetles under different conditions of land use in three Mexican biosphere reserves. In Montes Azules pastures, forest fragments and continuous rainforest were analyzed, in Los Tuxtlas rainforest fragments of different sizes were analyzed and in Barranca de Metztitlán two types of xerophile scrub with different degrees of disturbance from grazing were analyzed. We assigned dung beetle species to functional groups based on food relocation, beetle size, daily activity period and food preferences, and as measures of functional diversity we used estimates based on multivariate methods. In Montes Azules functional richness was lower in the pastures than in continuous rainforest and rainforest fragments, but fragments and continuous forest include functionally redundant species. In small rainforest fragments (20 ha). Functional evenness and functional dispersion did not vary among habitat types or fragment size in these reserves. In contrast, in Metztitlán, functional richness and functional dispersion were different among the vegetation types, but differences were not related to the degree of disturbance by grazing. More redundant species were found in submontane than in crassicaule scrub. For the first time, a decrease in the functional diversity in communities of copro-necrophagous beetles resulting from changes in land use is documented, the potential implications for ecosystem functioning are discussed and a series of variables that could improve the evaluation of functional diversity for this biological group is proposed. PMID:21448292

  9. Negative impacts of human land use on dung beetle functional diversity.

    Directory of Open Access Journals (Sweden)

    Felipe Barragán

    Full Text Available The loss of biodiversity caused by human activity is assumed to alter ecosystem functioning. However our understanding of the magnitude of the effect of these changes on functional diversity and their impact on the dynamics of ecological processes is still limited. We analyzed the functional diversity of copro-necrophagous beetles under different conditions of land use in three Mexican biosphere reserves. In Montes Azules pastures, forest fragments and continuous rainforest were analyzed, in Los Tuxtlas rainforest fragments of different sizes were analyzed and in Barranca de Metztitlán two types of xerophile scrub with different degrees of disturbance from grazing were analyzed. We assigned dung beetle species to functional groups based on food relocation, beetle size, daily activity period and food preferences, and as measures of functional diversity we used estimates based on multivariate methods. In Montes Azules functional richness was lower in the pastures than in continuous rainforest and rainforest fragments, but fragments and continuous forest include functionally redundant species. In small rainforest fragments (20 ha. Functional evenness and functional dispersion did not vary among habitat types or fragment size in these reserves. In contrast, in Metztitlán, functional richness and functional dispersion were different among the vegetation types, but differences were not related to the degree of disturbance by grazing. More redundant species were found in submontane than in crassicaule scrub. For the first time, a decrease in the functional diversity in communities of copro-necrophagous beetles resulting from changes in land use is documented, the potential implications for ecosystem functioning are discussed and a series of variables that could improve the evaluation of functional diversity for this biological group is proposed.

  10. Eos negatively regulates human γ-globin gene transcription during erythroid differentiation.

    Directory of Open Access Journals (Sweden)

    Hai-Chuan Yu

    Full Text Available BACKGROUND: Human globin gene expression is precisely regulated by a complicated network of transcription factors and chromatin modifying activities during development and erythropoiesis. Eos (Ikaros family zinc finger 4, IKZF4, a member of the zinc finger transcription factor Ikaros family, plays a pivotal role as a repressor of gene expression. The aim of this study was to examine the role of Eos in globin gene regulation. METHODOLOGY/PRINCIPAL FINDINGS: Western blot and quantitative real-time PCR detected a gradual decrease in Eos expression during erythroid differentiation of hemin-induced K562 cells and Epo-induced CD34+ hematopoietic stem/progenitor cells (HPCs. DNA transfection and lentivirus-mediated gene transfer demonstrated that the enforced expression of Eos significantly represses the expression of γ-globin, but not other globin genes, in K562 cells and CD34+ HPCs. Consistent with a direct role of Eos in globin gene regulation, chromatin immunoprecipitaion and dual-luciferase reporter assays identified three discrete sites located in the DNase I hypersensitivity site 3 (HS3 of the β-globin locus control region (LCR, the promoter regions of the Gγ- and Aγ- globin genes, as functional binding sites of Eos protein. A chromosome conformation capture (3C assay indicated that Eos may repress the interaction between the LCR and the γ-globin gene promoter. In addition, erythroid differentiation was inhibited by enforced expression of Eos in K562 cells and CD34+ HPCs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that Eos plays an important role in the transcriptional regulation of the γ-globin gene during erythroid differentiation.

  11. Mechanisms for the activity of heterocyclic cyclohexanone curcumin derivatives in estrogen receptor negative human breast cancer cell lines.

    Science.gov (United States)

    Somers-Edgar, Tiffany J; Taurin, Sebastien; Larsen, Lesley; Chandramouli, Anupama; Nelson, Mark A; Rosengren, Rhonda J

    2011-02-01

    Estrogen receptor (ER)-negative breast cancer is an aggressive form that currently requires more drug treatment options. Thus, we have further modified cyclohexanone derivatives of curcumin and examined them for cytotoxicity towards ER-negative human breast cancer cells. Two of the analogs screened elicited increased cytotoxic potency compared to curcumin and other previously studied derivatives. Specifically, 2,6-bis(pyridin-3-ylmethylene)-cyclohexanone (RL90) and 2,6-bis(pyridin-4-ylmethylene)-cyclohexanone (RL91) elicited EC(50) values of 1.54 and 1.10 µM, respectively, in MDA-MB-231 cells and EC(50) values of 0.51 and 0.23 in SKBr3 cells. All other new compounds examined were less potent than curcumin, which elicited EC(50) values of 7.6 and 2.4 µM in MDA-MB-231 and SKBr3 cells, respectively. Mechanistic analyses demonstrated that RL90 and RL91 significantly induced G(2)/M-phase cell cycle arrest and apoptosis. RL90 and RL91 also modulated the expression of key cell signaling proteins, specifically, in SKBr3 cells, protein levels of Her-2, Akt, and NFκB were decreased in a time-dependent manner, while activity of stress kinases JNK1/2 and P38 MAPK were increased. Signaling events in MDA-MB-231 cells were differently implicated, as EGFR protein levels were decreased and activity of GSK-3β transiently decreased, while β-catenin protein level and activity of P38 MAPK, Akt, and JNK1/2 were transiently increased. In conclusion replacement of the phenyl group of cyclohexanone derived curcumin derivatives with heterocyclic rings forms a class of second-generation analogs that are more potent than both curcumin and other derivatives. These new derivatives provide a platform for the further development of drugs for the treatment of ER-negative breast cancer.

  12. Negative Facial Expressions – But Not Visual Scenes – Enhance Human Working Memory in Younger and Older Participants

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    Flávia Schechtman Belham

    2017-09-01

    Full Text Available Many studies have investigated the influence of emotion on memory processes across the human lifespan. Some results have shown older adults (OA performing better with positive stimuli, some with negative items, whereas some found no impact of emotional valence. Here we tested, in two independent studies, how younger adults (YA and OA would perform in a visuospatial working memory (VSWM task with positive, negative, and neutral images. The task consisted of identifying the new location of a stimulus in a crescent set of identical stimuli presented in different locations in a touch-screen monitor. In other words, participants should memorize the locations previously occupied to identify the new location. For each trial, the number of occupied locations increased until 8 or until a mistake was made. In study 1, 56 YA and 38 OA completed the task using images from the International Affective Picture System (IAPS. Results showed that, although YA outperformed OA, no effects of emotion were found. In study 2, 26 YA and 25 OA were tested using facial expressions as stimuli. Data from this study showed that negative faces facilitated performance and this effect did not differ between age groups. No differences were found between men and women. Taken together, our findings suggest that YA and OA’s VSWM can be influenced by the emotional valence of the information, though this effect was present only for facial stimuli. Presumably, this may have happened due to the social and biological importance of such stimuli, which are more effective in transmitting emotions than IAPS images. Critically, our results also indicate that the mixed findings in the literature about the influence of aging on the interactions between memory and emotion may be caused by the use of different stimuli and methods. This possibility should be kept in mind in future studies about memory and emotion across the lifespan.

  13. Cerebral gumma mimicking a brain tumor in a human immunodeficiency virus-negative patient: A case report

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    Baek, Hye Jin; Kim, Woo Jin [Haeundae Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2013-09-15

    Syphilis has a broad spectrum of clinical manifestations, and the cerebral gumma is a kind of neurosyphilis which is rare and can be cured by appropriate antibiotic treatments. However, in clinical practices, diagnosis of cerebral syphilitic gumma is often difficult because imaging and laboratory findings revealed elusive results. Herein, we present a rare case of neurosyphilis presenting as cerebral gumma confirmed by histopathological examination, and positive serologic and cerebrospinal fluid analyses. This case report suggests that cerebral gumma should be considered as possible diagnosis for human immunodeficiency virus-negative patients with space-occupying lesion of the brain. And this case also provides importance of clinical suspicions in diagnosing neurosyphilis because syphilis serology is not routinely tested on patients with neurologic symptoms.

  14. Human lipoproteins have divergent neutralizing effects on E. coli LPS, N. meningitidis LPS, and complete Gram-negative bacteria.

    Science.gov (United States)

    Sprong, Tom; Netea, Mihai G; van der Ley, Peter; Verver-Jansen, Trees J G; Jacobs, Liesbeth E H; Stalenhoef, Anton; van der Meer, Jos W M; van Deuren, Marcel

    2004-04-01

    The use of lipoproteins has been suggested as a treatment for Gram-negative sepsis because they inhibit lipopolysaccharide (LPS)-mediated cytokine production. However, little is known about the neutralizing effects of lipoproteins on cytokine production by meningococcal LPS or whole Gram-negative bacteria. We assessed the neutralizing effect of LDLs, HDLs, and VLDLs on LPS- or whole bacteria-induced cytokines in human mononuclear cells. A strong inhibition of Escherichia coli LPS-induced interleukin-1beta (IL-1beta), tumor necrosis factor-alpha, and IL-10 by LDL and HDL was seen, whereas VLDL had a less pronounced effect. In contrast, Neisseria meningitidis LPS, in similar concentrations, was neutralized much less effectively than E. coli LPS. Effective neutralization of meningococcal LPS required a longer interaction time, a lower concentration of LPS, or higher concentrations of lipoproteins. The difference in neutralization was independent of the saccharide tail, suggesting that the lipid A moiety accounted for the difference. Minimal neutralizing effects of the lipoproteins were observed on whole E. coli or N. meningitidis bacteria under all conditions tested. These results indicate that efficient neutralization of LPS depends on the type of LPS, but a sufficiently long interaction time, a low LPS concentration, or high lipoprotein concentration also inhibited cytokines by the less efficiently neutralized N. meningitidis LPS. Irrespective of these differences, whole bacteria showed no neutralization by lipoproteins.

  15. G-CSF regulates macrophage phenotype and associates with poor overall survival in human triple-negative breast cancer.

    Science.gov (United States)

    Hollmén, Maija; Karaman, Sinem; Schwager, Simon; Lisibach, Angela; Christiansen, Ailsa J; Maksimow, Mikael; Varga, Zsuzsanna; Jalkanen, Sirpa; Detmar, Michael

    2016-03-01

    Tumor-associated macrophages (TAMs) have been implicated in the promotion of breast cancer growth and metastasis, and a strong infiltration by TAMs has been associated with estrogen receptor (ER)-negative tumors and poor prognosis. However, the molecular mechanisms behind these observations are unclear. We investigated macrophage activation in response to co-culture with several breast cancer cell lines (T47D, MCF-7, BT-474, SKBR-3, Cal-51 and MDA-MB-231) and found that high granulocyte colony-stimulating factor (G-CSF) secretion by the triple-negative breast cancer (TNBC) cell line MDA-MB-231 gave rise to immunosuppressive HLA-DR(lo) macrophages that promoted migration of breast cancer cells via secretion of TGF-α. In human breast cancer samples (n = 548), G-CSF was highly expressed in TNBC (p CSF-1R treatment promoted MHCII(lo)F4/80(hi)MR(hi) anti-inflammatory TAMs and enhanced lung metastasis in the presence of high G-CSF levels. Combined anti-G-CSF and anti-CSF-1R therapy significantly increased lymph node metastases, possibly via depletion of the so-called "gate-keeper" subcapsular sinus macrophages. These results indicate that G-CSF promotes the anti-inflammatory phenotype of tumor-induced macrophages when CSF-1R is inhibited and therefore caution against the use of M-CSF/CSF-1R targeting agents in tumors with high G-CSF expression.

  16. Effect of grape seed proanthocyanidins on tumor vasculogenic mimicry in human triple-negative breast cancer cells.

    Science.gov (United States)

    Luan, Yun-Yan; Liu, Zi-Min; Zhong, Jin-Yi; Yao, Ru-Yong; Yu, Hong-Sheng

    2015-01-01

    Vasculogenic mimicry (VM) refers to the unique ability of highly aggressive tumor cells to mimic the pattern of embryonic vasculogenesis, which was associated with invasion and metastasis. The grape seed proanthocyanidins (GSPs) had attracted much attention as a potential bioactive anti-carcinogenic agent. However, GSPs regulation of VM and its possible mechanisms in a triple-negative breast cancer cells (TNBCs) remain not clear. Therefore, we examined the effect of GSPs on VM information in HCC1937 cell model. In this study, we identified the VM structure via the three-dimensional (3D) matrix in vitro. Cell viability was measured using the CCK8 assay. The effects of GSPs on human triple-negative breast cancer cells (TNBCs) HCC1937 in terms of related proteins of VM information were determined using western blot analysis. In vitro, the tubular networks were found in highly invasive HCC1937 cells but not in the non-invasive MCF-7 cells when plated on matrigel. The number of vascular channels was significantly reduced when cells were exposed in GSPs (100 μg/ml) and GSPs (200 μg/ml) groups (all p<0.001). Furthermore, we found that treatment with GSPs promoted transition of the mesenchymal state to the epithelial state in HCC1937 cells as well as reducing the expression of Twist1 protein, a master EMT regulator.GSPs has the ability to inhibit VM information by the suppression of Twist1 protein that could be related to the reversal of epithelial-to-mesenchymal (EMT) process. It is firstly concluded that GSPs may be an potential anti-VM botanical agent for human TNBCs.

  17. Competing causes of death and medical comorbidities among patients with human papillomavirus-positive vs human papillomavirus-negative oropharyngeal carcinoma and impact on adherence to radiotherapy.

    Science.gov (United States)

    Hess, Clayton B; Rash, Dominique L; Daly, Megan E; Farwell, D Gregory; Bishop, John; Vaughan, Andrew T; Wilson, Machelle D; Chen, Allen M

    2014-04-01

    Survival of patients with head and neck cancer can be affected by competing causes of mortality, as well as comorbidities that result in radiation treatment interruptions. To discern how differences in preexisting medical and psychosocial comorbidities potentially influence adherence to radiation therapy according to human papillomavirus (HPV) status. Retrospective analysis at a comprehensive cancer center of 162 consecutive patients with locally advanced squamous cell carcinoma of the oropharynx treated with primary chemoradiation (n = 95) or primary surgery followed by adjuvant radiation (n = 67). Immunostaining for p16 was used to determine HPV status. Difference in alcohol, tobacco, and marijuana use was compared between patients with HPV-positive and HPV-negative tumors, as well as the prevalence of the following comorbidities: diabetes mellitus, chronic obstructive pulmonary disease (COPD), anxiety disorder, and major depression. The number of total missed treatment days was analyzed as both a continuous and categorical variable. Rates of self-reported heavy alcohol use (47% vs 16%; P = .02) and any marijuana use (47% vs 23%; P = .003) were significantly higher among HPV-negative patients. Fifty-four percent of HPV-positive patients self-identified as never smokers, compared with only 12% of HPV-negative patients (P rate of at least 5 missed days (24% vs 10%; P = .04), and higher prevalences of COPD (12% vs 7%; P = .37) and anxiety disorder (12% vs 6%; P = .35). Pronounced differences exist in lifestyle habits between patients with HPV-negative and HPV-positive oropharyngeal cancer at diagnosis. These differences, as well as those of medical and psychosocial burden, may contribute to observed discrepancies in treatment adherence and need to be considered in outcomes reporting and clinical trial design.

  18. Tumor suppressor protein p53 exerts negative transcriptional regulation on human sodium iodide symporter gene expression in breast cancer.

    Science.gov (United States)

    Kelkar, Madhura G; Thakur, Bhushan; Derle, Abhishek; Chatterjee, Sushmita; Ray, Pritha; De, Abhijit

    2017-08-01

    Aberrant expression of human sodium iodide symporter (NIS) in breast cancer (BC) is well documented but the transcription factors (TF) regulating its aberrant expression is poorly known. We identify the presence of three p53 binding sites on the human NIS promoter sequence by conducting genome-wide TF analysis, and further investigate their regulatory role. The differences in transcription and translation were measured by real-time PCR, luciferase reporter assay, site-directed mutagenesis, in vivo optical imaging, and chromatin immunoprecipitation. The relation of NIS and p53 in clinical samples was judged by TCGA data analysis and immunohistochemistry. Overexpression of wild-type p53 as a transgene or pharmacological activation by doxorubicin drug treatment shows significant suppression of NIS transcription in multiple BC cell types which also results in lowered NIS protein content and cellular iodide intake. NIS repression by activated p53 is further confirmed by non-invasive bioluminescence imaging in live cell and orthotropic tumor model. Abrogation of p53-binding sites by directional mutagenesis confirms reversal of transcriptional activity in wild-type p53-positive BC cells. We also observe direct binding of p53 to these sites on the human NIS promoter. Importantly, TCGA data analysis of NIS and p53 co-expression registers an inverse relationship between the two candidates. Our data for the first time highlight the role of p53 as a negative regulator of functional NIS expression in BC, where the latter is a potential targeted radioiodine therapy candidate. Thus, the study provides an important insight into prospective clinical application of this approach that may significantly impact the patient with mutant versus wild-type p53 profile.

  19. Non-negative matrix factorisation methods for the spectral decomposition of MRS data from human brain tumours

    Directory of Open Access Journals (Sweden)

    Ortega-Martorell Sandra

    2012-03-01

    Full Text Available Abstract Background In-vivo single voxel proton magnetic resonance spectroscopy (SV 1H-MRS, coupled with supervised pattern recognition (PR methods, has been widely used in clinical studies of discrimination of brain tumour types and follow-up of patients bearing abnormal brain masses. SV 1H-MRS provides useful biochemical information about the metabolic state of tumours and can be performed at short ( 45 ms echo time (TE, each with particular advantages. Short-TE spectra are more adequate for detecting lipids, while the long-TE provides a much flatter signal baseline in between peaks but also negative signals for metabolites such as lactate. Both, lipids and lactate, are respectively indicative of specific metabolic processes taking place. Ideally, the information provided by both TE should be of use for clinical purposes. In this study, we characterise the performance of a range of Non-negative Matrix Factorisation (NMF methods in two respects: first, to derive sources correlated with the mean spectra of known tissue types (tumours and normal tissue; second, taking the best performing NMF method for source separation, we compare its accuracy for class assignment when using the mixing matrix directly as a basis for classification, as against using the method for dimensionality reduction (DR. For this, we used SV 1H-MRS data with positive and negative peaks, from a widely tested SV 1H-MRS human brain tumour database. Results The results reported in this paper reveal the advantage of using a recently described variant of NMF, namely Convex-NMF, as an unsupervised method of source extraction from SV1H-MRS. Most of the sources extracted in our experiments closely correspond to the mean spectra of some of the analysed tumour types. This similarity allows accurate diagnostic predictions to be made both in fully unsupervised mode and using Convex-NMF as a DR step previous to standard supervised classification. The obtained results are comparable to

  20. Doxycycline inhibits proliferation and induces apoptosis of both human papillomavirus positive and negative cervical cancer cell lines.

    Science.gov (United States)

    Zhao, Yan; Wang, Xinyu; Li, Lei; Li, Changzhong

    2016-05-01

    The clinical management of cervical cancer remains a challenge and the development of new treatment strategies merits attention. However, the discovery and development of novel compounds can be a long and labourious process. Drug repositioning may circumvent this process and facilitate the rapid translation of hypothesis-driven science into the clinics. In this work, we show that a FDA-approved antibiotic, doxycycline, effectively targets human papillomavirus (HPV) positive and negative cervical cancer cells in vitro and in vivo. Doxycycline significantly inhibits proliferation of a panel of cervical cancer cell lines. It also induces apoptosis of cervical cancer cells in a time- and dose-dependent manner. In addition, the apoptosis induced by doxycycline is through caspase-dependent pathway. Mechanism studies demonstrate that doxycycline affects oxygen consumption rate, glycolysis, and reduces ATP levels in cervical cancer cells. In HeLa xenograft mouse model, doxycycline significantly inhibits growth of tumour. Our in vitro and in vivo data clearly demonstrate the inhibitory effects of doxycycline on the growth and survival of cervical cancer cells. Our work provides the evidence that doxycycline can be repurposed for the treatment of cervical cancer and targeting energy metabolism may represent a potential therapeutic strategy for cervical cancer.

  1. Human immunodeficiency virus (HIV)-negative, API2-MALT1 fusion-negative bronchus-associated lymphoid tissue (BALT) lymphoma in a young male.

    Science.gov (United States)

    Okamoto, Masashi; Inaba, Tohru; Uchida, Ryo; Fuchida, Shinichi; Ochiai, Naoya; Okano, Akira; Ashihara, Eishi; Inagaki, Hiroshi; Nakamura, Shigeo; Shimazaki, Chihiro

    2004-10-01

    A 22-year-old male presented with multiple bilateral nodular shadows in the lungs by chest radiograph. He had been asymptomatic and showed no significant abnormal findings in laboratory examinations. He underwent a diagnostic partial lobectomy, and was diagnosed as having primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma; i.e. bronchus-associated lymphoid tissue (BALT) lymphoma/BALToma. Neither t(11;18)(q21;q21) chromosomal translocation nor API2-MALT1 chimeric transcript was found at diagnosis. Epstein-Barr virus (EBV) was also not detected in lymphoma cells. He had been a nonsmoker, and had also never shown any associated autoimmune disorders, chronic inflammatory lung diseases or human immunodeficiency virus (HIV) infection. However, he had suffered from moderate atopic dermatitis on his arms from childhood. It appears necessary to clarify whether atopy might play a role in the pathogenesis of API2-MALT1(-) BALT lymphoma for HIV(-) young patients who do not exhibit any other antecedent chronic antigenic stimulations.

  2. Challenges Facing the Use of Human Rights to Address Negative Impacts of Development: the Case of Indonesia

    NARCIS (Netherlands)

    Istiningsih-Hadiprayitno, I.

    2011-01-01

    The importance of human rights in development is gaining prominence. In concrete settings and contexts, however, contesting development practices with human rights normative standards is controversial. The article outlines this controversy and complexity in Indonesia. It highlights tensions in human

  3. Feline mammary basal-like adenocarcinomas: a potential model for human triple-negative breast cancer (TNBC) with basal-like subtype.

    Science.gov (United States)

    Wiese, David A; Thaiwong, Tuddow; Yuzbasiyan-Gurkan, Vilma; Kiupel, Matti

    2013-09-03

    Breast cancer is one of the leading causes of cancer deaths. Triple-negative breast cancer (TNBC), an immunophenotype defined by the absence of immunolabeling for estrogen receptor (ER), progesterone receptor (PR) and HER2 protein, has a highly aggressive behavior. A subpopulation of TNBCs exhibit a basal-like morphology with immunohistochemical positivity for cytokeratins 5/6 (CK5/6) and/or epidermal growth factor receptor (EGFR), and have a high incidence of BRCA (breast cancer susceptibility) mutations. Feline mammary adenocarcinomas (FMAs) are highly malignant and share a similar basal-like subtype. The purpose of this study was to classify FMAs according to the current human classification of breast cancer that includes evaluation of ER, PR and HER2 status and expression of basal CK 5/6 and EGFR. Furthermore, we selected triple negative, basal-like FMAs to screen for BRCA mutations similar to those described in human TNBC. Twenty four FMAs were classified according to the current human histologic breast cancer classification including immunohistochemistry (IHC) for ER, PR HER2, CK5/6 and EGFR. Genetic alteration and loss of heterozygosity of BRCA1 and BRCA2 genes were analyzed in triple negative, basal-like FMAs. IHC for ER, PR and HER2 identified 14 of the 24 (58%) FMAs as a triple negative. Furthermore, 11 of these 14 (79%) triple negative FMAs had a basal-like subtype. However, no genetic abnormalities were detected in BRCA1 and BRCA2 by direct sequencing and loss of heterozygosity analysis. FMAs are highly aggressive neoplasms that are commonly triple negative and exhibit a basal-like morphology. This is similar to human TNBC that are also commonly classified as a basal-like subtype. While sequencing of a select number of triple negative, basal-like FMAs and testing for loss of heterozygosity of BRCA1 and BRCA2 did not identify mutations similar to those described in human TNBC, further in-depth evaluation is required to elucidate a potential role of BRCA

  4. Negative regulation of glucose metabolism in human myotubes by supraphysiological doses of 17β-estradiol or testosterone.

    Science.gov (United States)

    Garrido, Pablo; Salehzadeh, Firoozeh; Duque-Guimaraes, Daniella E; Al-Khalili, Lubna

    2014-09-01

    Exposure of skeletal muscle to high levels of testosterone or estrogen induces insulin resistance, but evidence regarding the direct role of either sex hormone on metabolism is limited. Therefore, the aim of this study was to investigate the direct effect of acute sex hormone exposure on glucose metabolism in skeletal muscle. Differentiated human skeletal myotubes were exposed to either 17β-estradiol or testosterone and metabolic characteristics were assessed. Glucose incorporation into glycogen, glucose oxidation, palmitate oxidation, and phosphorylation of key signaling proteins were determined. Treatment of myotubes with either 17β-estradiol or testosterone decreased glucose incorporation into glycogen. Exposure of myotubes to 17β-estradiol reduced glucose oxidation under basal and insulin-stimulated conditions. However, testosterone treatment enhanced basal palmitate oxidation and prevented insulin action on glucose and palmitate oxidation. Acute stimulation of myotubes with testosterone reduced phosphorylation of S6K1 and p38 MAPK. Exposure of myotubes to either 17β-estradiol or testosterone augmented phosphorylation GSK3β(Ser9) and PKCδ(Thr505), two negative regulators of glycogen synthesis. Treatment of myotubes with a PKC specific inhibitor (GFX) restored the effect of either sex hormone on glycogen synthesis. PKCδ silencing restored glucose incorporation into glycogen to baseline in response to 17β-estradiol, but not testosterone treatment. An acute exposure to supraphysiological doses of either 17β-estradiol or testosterone regulates glucose metabolism, possibly via PKC signaling pathways. Furthermore, testosterone treatment elicits additional alterations in serine/threonine kinase signaling, including the ribosomal protein S6K1 and p38 MAPK. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer.

    Science.gov (United States)

    Boér, Katalin

    2016-01-01

    Breast cancer is a heterogeneous disease with multiple subgroups based on clinical and molecular characteristics. For the largest subgroup of breast cancers, hormone receptor-positive/human epidermal growth factor 2 (HER2)-negative tumors, hormone treatment is the mainstay of therapy and is likely to result in significant improvement in disease outcomes. However, some of these cancers demonstrate de novo or acquired resistance to endocrine therapy. Despite intensive research to develop new strategies to enhance the efficacy of currently available treatment options for hormone receptor-positive breast cancer, progress has been slow, and there were few advances for a period of 10 years. In 2012, a new molecularly targeted therapeutic strategy, inhibition of mammalian target of rapamycin with everolimus, was introduced into clinical practice. Everolimus, in combination with a steroidal aromatase inhibitor, exemestane, resulted in an increase in progression-free survival, but not overall survival in patients with estrogen receptor (ER)+ve advanced disease who had progressed on hormone therapy. In 2015, the first cyclin-dependent kinases 4/6 (CDK4/6) inhibitor, palbociclib, received accelerated US Food and Drug Administration approval for use in combination with letrozole for the treatment of postmenopausal ER+ve/HER2-ve advanced breast cancer as initial, endocrine-based therapy. The addition of palbociclib to endocrine therapy resulted in longer progression-free survival than letrozole alone. One year later, palbociclib received a new indication, use in combination with fulvestrant, in both premenopausal and postmenopausal females with advanced breast cancer of the same subtype with disease progression following endocrine therapy. Adding palbociclib to fulvestrant resulted in a significantly increased median progression-free survival compared to fulvestrant monotherapy. These new combination regimens of palbociclib with endocrine agents represent an important addition

  6. Comparison of urine samples and penile swabs for detection of human papillomavirus in HIV-negative Dutch men.

    Science.gov (United States)

    Koene, Fleur; Wolffs, Petra; Brink, Antoinette; Dukers-Muijrers, Nicole; Quint, Wim; Bruggeman, Cathrien; Hoebe, Christian

    2016-09-01

    Penile swab sampling is the method of choice when testing for human papillomavirus (HPV) in men. Urine sampling is already used in routine sexually transmitted infections (STI) diagnostics and could provide a less invasive sampling method in men to detect HPV. Therefore we compared detection of HPV types in urine samples and penile swabs by the highly sensitive SPF10-LiPA25 system. First void urine and self-obtained penile swab samples were collected from 120 men, with a mean age of 29.4 years, visiting a STI clinic in South Limburg, the Netherlands. In total 111 of 120 men were included in the analysis. Broad-spectrum HPV DNA amplification and mucosal HPV genotyping were performed using the SPF10 DEIA-LiPA25 system (SPF10 HPV LiPA, V.1). In total 75 (68%) men were positive for HPV in the combined analysis. Sixty-six (59%) paired samples were concordant in being positive or negative. In 39% of the men HPV DNA was detected only in the penile swab. In 2% of the men HPV DNA was detected only in the urine sample. Considering penile swabs as the gold standard, a sensitivity of 41% (95% CI 30% to 53%) and a specificity of 95% (95% CI 81% to 99%) was found. In 6 (5%) urines high risk types were repeatedly found that were not detected in the matching swab. Urine samples are not comparable to penile swabs in the detection of HPV in men. However, the addition of urine samples to penile swabs could be of use in epidemiological or clearance studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  7. Human lipoproteins have divergent neutralizing effects on E. coli LPS, N. meningitidis LPS, and complete Gram-negative bacteria.

    NARCIS (Netherlands)

    Sprong, T.; Netea, M.G.; Ley, P. van der; Verver-Jansen, T.J.G.; Jacobs, L.E.; Stalenhoef, A.F.H.; Meer, J.W.M. van der; Deuren, M. van

    2004-01-01

    The use of lipoproteins has been suggested as a treatment for Gram-negative sepsis because they inhibit lipopolysaccharide (LPS)-mediated cytokine production. However, little is known about the neutralizing effects of lipoproteins on cytokine production by meningococcal LPS or whole Gram-negative

  8. Humanizing online brand communications in response to negative word of mouth: the effects of proactive and reactive webcare

    NARCIS (Netherlands)

    van Noort, G.; Willemsen, L.M.; Eisend, M.; Langner, T.

    2011-01-01

    By means of an experiment, we study the most effective means for companies to counter complaints as expressed in negative electronic word of mouth (NWOM). The results show that negative brand evaluations engendered by NWOM, can be attenuated by webcare interventions dependent on type of strategy

  9. Correlates of Human Immunodeficiency Virus/Sexually Transmitted Infection (HIV/STI) Testing and Disclosure among HIV-Negative Collegiate Men Who Have Sex with Men

    Science.gov (United States)

    Wilkerson, J. Michael; Fuchs, Erika L.; Brady, Sonya S.; Jones-Webb, Rhonda; Rosser, B. R. Simon

    2014-01-01

    Objective: To determine the extent to which personal, behavioral, and environmental factors are associated with human immunodeficiency virus/sexually transmitted infection (HIV/STI) testing and disclosure. Participants: Nine hundred thirty HIV-negative collegiate men who have sex with men (MSM) who completed an online survey about alcohol use and…

  10. Performance of visual inspection with acetic acid and human papillomavirus testing for detection of high-grade cervical lesions in HIV positive and HIV negative Tanzanian women

    DEFF Research Database (Denmark)

    Dartell, Myassa Arkam; Rasch, Vibeke; Iftner, Thomas

    2014-01-01

    The aim of this cross sectional study was to assess type distribution of human papillomavirus (HPV) among HIV positive and HIV negative women who underwent cervical cancer screening, and to examine the ability of visual inspection with acetic acid (VIA), the standard detection method in Tanzania...

  11. Detection of oncogenic genital human papillomavirus (HPV) among HPV negative older and younger women after 7 years of follow-up

    DEFF Research Database (Denmark)

    Brogaard, Kim Agerholm; Munk, Christian; Iftner, Thomas

    2014-01-01

    The knowledge on risk factors of being human papillomavirus (HPV)-positive among older women is sparse. The aim was to determine the frequency of oncogenic HPV appearance after 7 years among initially HPV-negative women and to examine potential risk factors that influence the occurrence of HPV...

  12. Sexual Transmission of Hepatitis C Virus in Human Immunodeficiency Virus-Negative Men Who Have Sex With Men: A Series of Case Reports

    NARCIS (Netherlands)

    van de Laar, Thijs J. W.; Paxton, William A.; Zorgdrager, Fokla; Cornelissen, Marion; de Vries, Henry J. C.

    2011-01-01

    Hepatitis C Virus (HCV) has recently emerged as sexual transmitted infection among (human immunodeficiency virus) HIV-positive but not HIV-negative men who have sex with men (MSM). We present 4 case reports showing that HIV-infection is not an absolute prerequisite for sexual HCV transmission in

  13. Impact of palbociclib combinations on treatment of advanced estrogen receptor-positive/human epidermal growth factor 2-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Boér K

    2016-10-01

    Full Text Available Katalin Boér Department of Medical Oncology, Szent Margit Hospital, Budapest, Hungary Abstract: Breast cancer is a heterogeneous disease with multiple subgroups based on clinical and molecular characteristics. For the largest subgroup of breast cancers, hormone receptor-positive/human epidermal growth factor 2 (HER2-negative tumors, hormone treatment is the mainstay of therapy and is likely to result in significant improvement in disease outcomes. However, some of these cancers demonstrate de novo or acquired resistance to endocrine therapy. Despite intensive research to develop new strategies to enhance the efficacy of currently available treatment options for hormone receptor-positive breast cancer, progress has been slow, and there were few advances for a period of 10 years. In 2012, a new molecularly targeted therapeutic strategy, inhibition of mammalian target of rapamycin with everolimus, was introduced into clinical practice. Everolimus, in combination with a steroidal aromatase inhibitor, exemestane, resulted in an increase in progression-free survival, but not overall survival in patients with estrogen receptor (ER+ve advanced disease who had progressed on hormone therapy. In 2015, the first cyclin-dependent kinases 4/6 (CDK4/6 inhibitor, palbociclib, received accelerated US Food and Drug Administration approval for use in combination with letrozole for the treatment of postmenopausal ER+ve/HER2-ve advanced breast cancer as initial, endocrine-based therapy. The addition of palbociclib to endocrine therapy resulted in longer progression-free survival than letrozole alone. One year later, palbociclib received a new indication, use in combination with fulvestrant, in both premenopausal and postmenopausal females with advanced breast cancer of the same subtype with disease progression following endocrine therapy. Adding palbociclib to fulvestrant resulted in a significantly increased median progression-free survival compared to fulvestrant

  14. Associations Between Exposure to and Expression of Negative Opinions About Human Papillomavirus Vaccines on Social Media: An Observational Study

    National Research Council Canada - National Science Library

    Dunn, Adam G; Leask, Julie; Zhou, Xujuan; Mandl, Kenneth D; Coiera, Enrico

    2015-01-01

    Groups and individuals that seek to negatively influence public opinion about the safety and value of vaccination are active in online and social media and may influence decision making within some communities...

  15. Polymerase Chain Reaction Human Papillomavirus (HPV) Detection and HPV Genotyping in Invasive Cervical Cancers With Prior Negative HC2 Test Results.

    Science.gov (United States)

    Tao, Xiang; Zheng, Baowen; Yin, Fufen; Zeng, Zhengyu; Li, Zaibo; Griffith, Christopher C; Luo, Bing; Ding, Xiangdong; Zhou, Xianrong; Zhao, Chengquan

    2017-05-01

    Recently, three large Chinese cohort studies showed that 7.5% to 15.5% of patients with cervical carcinoma had negative high-risk human papillomavirus (hrHPV) test results on prior cytology specimens. These studies raise the question as to whether these negative hrHPV results represent truly hrHPV-negative carcinomas or false-negative hrHPV test results due to limitations in the testing of cytology specimens. This is increasingly an important question with increasing push to use hrHPV testing alone to screen for cervical cancer. We investigated the hrHPV status on the surgical specimens from these same patients with cervical carcinoma using three polymerase chain reaction methods and a linear assay genotyping method. A variety of HPV genotypes were detected in 28 (45.9%) of 61 cases, all belonging to carcinogenic or possibly carcinogenic categories. HPV 16 was the most common genotype detected in positive cases (66.7%). HPV was detected in 25 (50%) of 50 squamous cell carcinomas and two (66.7%) of three adenosquamous carcinomas and only one (12.5%) of eight endocervical adenocarcinomas. Our findings demonstrate that negative hrHPV testing on cervicovaginal cytology specimens in women later diagnosed with cervical carcinoma can be explained by the occurrence of truly HPV-negative carcinomas in more than half of patients. These results should be considered in the development of future cervical cancer screening guidelines.

  16. Management of serology negative human hepatic hydatidosis (caused by Echinococcus granulosus) in a young woman from Bangladesh in a resource-rich setting: A case report.

    Science.gov (United States)

    Griffin, Daniel O; Donaghy, Henry J; Edwards, Barbara

    2014-01-01

    Human cystic echinococcosis (hydatidosis) is a parasitic zoonosis with almost complete worldwide distribution. Echinococcus granulosus, the dog tapeworm, causes hydatidosis which accounts for 95% of human echinococcosis. Although this tapeworm is found in dogs as a definitive host and a number of intermediate hosts, humans are often infected from close contact with infected dogs. Humans are not part of the parasitic lifecycle and serve as accidental hosts. Hydatidosis is an important consideration in the differential diagnosis of hepatic cysts in individuals from endemic areas. Clinicians should be aware of the long incubation period, the high frequency of negative serological tests, and the possibility of intraoperative evaluations of the cyst aspirate being non-diagnostic. We describe a case of serology negative hydatidosis that came to medical attention as an incidental finding in a young woman from Bangladesh. The patient underwent imaging and was then started on albendazole. After several weeks of albendazole, the cyst was punctured, aspirated, injected with hypertonic saline, re-aspirated, and then fully excised. Diagnosis was confirmed by microscopic evaluation of the cyst aspirate. Serological tests for hydatidosis may be negative in patients with early disease and thus should not be used to rule out this disease. Consideration of this diagnosis allows clinicians to avoid the catastrophic spillage of cystic contents risking an anaphylactic reaction, which might prove fatal. Despite World Health Organization hydatidosis staging being based on ultrasound, radiologists in resource-rich setting may prefer MRI in the management and staging of cystic echinococcosis.

  17. FA1 immunoreactivity in endocrine tumours and during development of the human fetal pancreas; negative correlation with glucagon expression

    DEFF Research Database (Denmark)

    Tornehave, D; Jensen, Charlotte Harken; Teisner, B

    1996-01-01

    tumours. A negative correlation between FA1 and glucagon immunoreactants in these tumours prompted a reexamination of FA1 immunoreactants during fetal pancreatic development. At the earliest stages of development, FA1 was expressed by most of the non-endocrine parenchymal cells and, with ensuing...... development, gradually disappeared from these cells and became restricted to insulin-producing beta cells. Throughout development FA1 was not detected in endocrine glucagon, somatostatin or pancreatic polypeptide cells. Moreover, developing insulin cells that coexpressed glucagon were negative for FA1. Thus......, there was a negative correlation between FA1 and glucagon both in tumours and during development. These results, together with FA1/dlk's similarity with homeotic proteins, point to a role of FA1 in islet cell differentiation. Udgivelsesdato: 1996-Dec...

  18. Risk Factors for High-Risk Human Papillomavirus Detection Among HIV-Negative and HIV-Positive Women From Tanzania

    DEFF Research Database (Denmark)

    Dartell, Myassa Arkam; Rasch, Vibeke; Munk, Christian

    2013-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The prevalence is dependent on several known factors notably sexual behavior and age, and factors still under scrutiny.......Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The prevalence is dependent on several known factors notably sexual behavior and age, and factors still under scrutiny....

  19. Of Men Not Mice: Bactericidal/Permeability-Increasing Protein Expressed in Human Macrophages Acts as a Phagocytic Receptor and Modulates Entry and Replication of Gram-Negative Bacteria

    Science.gov (United States)

    Balakrishnan, Arjun; Schnare, Markus; Chakravortty, Dipshikha

    2016-01-01

    Macrophages as immune cells prevent the spreading of pathogens by means of active phagocytosis and killing. We report here the presence of an antimicrobial protein, bactericidal/permeability-increasing protein (BPI) in human macrophages, which actively participates in engulfment and killing of Gram-negative pathogens. Our studies revealed increased expression of BPI in human macrophages during bacterial infection and upon stimulation with various pathogen-associated molecular patterns, viz., LPS and flagellin. Furthermore, during the course of an infection, BPI interacted with Gram-negative bacteria, resulting in enhanced phagocytosis and subsequent control of the bacterial replication. However, it was observed that bacteria which can maintain an active replicating niche (Salmonella Typhimurium) avoid the interaction with BPI during later stages of infection. On the other hand, Salmonella mutants, which cannot maintain a replicating niche, as well as Shigella flexneri, which quit the endosomal vesicle, showed interaction with BPI. These results propose an active role of BPI in Gram-negative bacterial clearance by human macrophages. PMID:27822215

  20. Determinants of Human Immunodeficiency Virus (HIV prevalence in homosexual and bisexual men screened for admission to a cohort study of HIV negatives in Belo Horizonte, Brazil: Project Horizonte

    Directory of Open Access Journals (Sweden)

    Carneiro Mariângela

    2003-01-01

    Full Text Available Project Horizonte, an open cohort of homosexual and bisexual human immunodeficiency virus (HIV-1 negative men, is a component of the AIDS Vaccine Program, in Belo Horizonte, Minas Gerais, Brazil. The objective of this study was to compare volunteers testing HIV positive at cohort entry with a sample of those who tested HIV negative in order to identify risk factors for prevalent HIV infection, in a population being screened for enrollment at Project Horizonte. A nested case-control study was conducted. HIV positive volunteers at entry (cases were matched by age and admission date to three HIV negative controls each. Selected variables used for the current analysis included demographic factors, sexual behavior and other risk factors for HIV infection. During the study period (1994-2001, among the 621 volunteers screened, 61 tested positive for HIV. Cases were matched to 183 HIV negative control subjects. After adjustments, the main risk factors associated with HIV infection were unprotected sex with an occasional partners, OR = 3.7 (CI 95% 1.3-10.6, receptive anal intercourse with an occasional partner, OR = 2.8 (95% CI 0.9-8.9 and belonging to the negro racial group, OR = 3.4 (CI 95% 1.1-11.9. These variables were associated with an increase in the risk of HIV infection among men who have sex with men at the screening for admission to an open HIV negative cohort.

  1. Human leukocyte antigen Class II associations in serum antimitochondrial antibodies (AMA)-positive and AMA-negative primary biliary cirrhosis.

    Science.gov (United States)

    Stone, Julianne; Wade, Judy A; Cauch-Dudek, Karen; Ng, Chang; Lindor, Keith D; Heathcote, E Jenny

    2002-01-01

    An association of Class II HLA-DR8 antigen is reported in patients with serum antimitochondrial antibodies (AMA)-positive primary biliary cirrhosis (PBC); no information exists as to an association with AMA-negative PBC. We compared the frequency of HLA Class II genes in AMA-positive and AMA-negative PBC patients and healthy controls. Genomic DNA was extracted from the blood of 154 AMA-positive and 26 AMA-negative Caucasian PBC patients and from 216 healthy Caucasian controls and tested for the alleles at two HLA Class II loci, DRbeta1 and DQbeta1. Higher allele frequencies of HLA-DRbeta1*08 and DQbeta1*04 were found in the AMA-positive PBC patients versus controls (14.9% vs. 6.5%, odds ratio (OR)=3.3, global P=0.03 and 14.4% vs. 6.5%, OR=2.6, global P=0.002). All patients positive for DRbeta1*0801 were positive for the DQbeta1*0402 allele, delta score=22 for AMA-positive patients, 11 for controls. In AMA-negative PBC, the frequency of DRbeta1*08 and DQbeta1*04 was 0%, significantly different from the AMA-positive patients (P=0.05, P=0.05). AMA response may identify a group of PBC patients with a distinctive expression of the disease with the response associated with a gene(s) in the class II region of the major histocompatibility complex on the short arm of chromosome 6.

  2. Glucocorticoids induce CCN5/WISP-2 expression and attenuate invasion in oestrogen receptor-negative human breast cancer cells.

    Science.gov (United States)

    Ferrand, Nathalie; Stragier, Emilien; Redeuilh, Gérard; Sabbah, Michèle

    2012-10-01

    CCN5 (cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed 5)/WISP-2 [WNT1 (wingless-type MMTV integration site family, member 1)-inducible signalling pathway protein 2] is an oestrogen-regulated member of the CCN family. CCN5 is a transcriptional repressor of genes associated with the EMT (epithelial-mesenchymal transition) and plays an important role in maintenance of the differentiated phenotype in ER (oestrogen receptor)-positive breast cancer cells. In contrast, CCN5 is undetectable in more aggressive ER-negative breast cancer cells. We now report that CCN5 is induced in ER-negative breast cancer cells such as MDA-MB-231 following glucocorticoid exposure, due to interaction of the endogenous glucocorticoid receptor with a functional glucocorticoid-response element in the CCN5 gene promoter. Glucocorticoid treatment of MDA-MB-231 cells is accompanied by morphological alterations, decreased invasiveness and attenuated expression of mesenchymal markers, including vimentin, cadherin 11 and ZEB1 (zinc finger E-box binding homeobox 1). Interestingly, glucocorticoid exposure did not increase CCN5 expression in ER-positive breast cancer cells, but rather down-regulated ER expression, thereby attenuating oestrogen pathway signalling. Taken together, our results indicate that glucocorticoid treatment of ER-negative breast cancer cells induces high levels of CCN5 expression and is accompanied by the appearance of a more differentiated and less invasive epithelial phenotype. These findings propose a novel therapeutic strategy for high-risk breast cancer patients.

  3. Evaluation of the in vitro growth of urinary tract infection-causing gram-negative and gram-positive bacteria in a proposed synthetic human urine (SHU) medium.

    Science.gov (United States)

    Ipe, Deepak S; Ulett, Glen C

    2016-08-01

    Bacteriuria is a hallmark of urinary tract infection (UTI) and asymptomatic bacteriuria (ABU), which are among the most frequent infections in humans. A variety of gram-negative and gram-positive bacteria are associated with these infections but Escherichia coli contributes up to 80% of cases. Multiple bacterial species including E. coli can grow in human urine as a means to maintain colonization during infections. In vitro bacteriuria studies aimed at modeling microbial growth in urine have utilized various compositions of synthetic human urine (SHU) and a Composite SHU formulation was recently proposed. In this study, we sought to validate the recently proposed Composite SHU as a medium that supports the growth of several bacterial species that are known to grow in normal human urine and/or artificial urine. Comparative growth assays of gram-negative and gram-positive bacteria E. coli, Pseudomonas aeruginosa, Proteus mirabilis, Streptococcus agalactiae, Staphylococcus saprophyticus and Enterococcus faecalis were undertaken using viable bacterial count and optical density measurements over a 48h culture period. Three different SHU formulations were tested in various culture vessels, shaking conditions and volumes and showed that Composite SHU can support the robust growth of gram-negative bacteria but requires supplementation with 0.2% yeast extract to support the growth of gram-positive bacteria. Experiments are also presented that show an unexpected but major influence of P. mirabilis towards the ability to measure bacterial growth in generally accepted multiwell assays using absorbance readings, predicted to have a basis in the release of volatile organic compound(s) from P. mirabilis during growth in Composite SHU medium. This study represents an essential methodological validation of a more chemically defined type of synthetic urine that can be applied to study mechanisms of bacteriuria and we conclude will offer a useful in vitro model to investigate the

  4. Positive or negative feedback of optokinetic signals: degree of the misrouted optic flow determines system dynamics of human ocular motor behavior.

    Science.gov (United States)

    Chen, Chien-Cheng; Bockisch, Christopher J; Olasagasti, Itsaso; Weber, Konrad P; Straumann, Dominik; Huang, Melody Ying-Yu

    2014-04-09

    The optokinetic system in healthy humans is a negative-feedback system that stabilizes gaze: slow-phase eye movements (i.e., the output signal) minimize retinal slip (i.e., the error signal). A positive-feedback optokinetic system may exist due to the misrouting of optic fibers. Previous studies have shown that, in a zebrafish mutant with a high degree of the misrouting, the optokinetic response (OKR) is reversed. As a result, slow-phase eye movements amplify retinal slip, forming a positive-feedback optokinetic loop. The positive-feedback optokinetic system cannot stabilize gaze, thus leading to spontaneous eye oscillations (SEOs). Because the misrouting in human patients (e.g., with a condition of albinism or achiasmia) is partial, both positive- and negative-feedback loops co-exist. How this co-existence affects human ocular motor behavior remains unclear. We presented a visual environment consisting of two stimuli in different parts of the visual field to healthy subjects. One mimicked positive-feedback optokinetic signals and the other preserved negative-feedback optokinetic signals. By changing the ratio and position of the visual field of these visual stimuli, various optic nerve misrouting patterns were simulated. Eye-movement responses to stationary and moving stimuli were measured and compared with computer simulations. The SEOs were correlated with the magnitude of the virtual positive-feedback optokinetic effect. We found a correlation among the simulated misrouting, the corresponding OKR, and the SEOs in humans. The proportion of the simulated misrouting needed to be greater than 50% to reverse the OKR and at least greater than or equal to 70% to evoke SEOs. Once the SEOs were evoked, the magnitude positively correlated to the strength of the positive-feedback OKR. This study provides a mechanism of how the misrouting of optic fibers in humans could lead to SEOs, offering a possible explanation for a subtype of infantile nystagmus syndrome (INS).

  5. Myostatin acts as an autocrine/paracrine negative regulator in myoblast differentiation from human induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Fei; Kishida, Tsunao; Ejima, Akika [Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto (Japan); Gojo, Satoshi [Department of Cardiac Support, Kyoto Prefectural University of Medicine, Kyoto (Japan); Mazda, Osam, E-mail: mazda@koto.kpu-m.ac.jp [Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto (Japan)

    2013-02-08

    Highlights: ► iPS-derived cells express myostatin and its receptor upon myoblast differentiation. ► Myostatin inhibits myoblast differentiation by inhibiting MyoD and Myo5a induction. ► Silencing of myostatin promotes differentiation of human iPS cells into myoblasts. -- Abstract: Myostatin, also known as growth differentiation factor (GDF-8), regulates proliferation of muscle satellite cells, and suppresses differentiation of myoblasts into myotubes via down-regulation of key myogenic differentiation factors including MyoD. Recent advances in stem cell biology have enabled generation of myoblasts from pluripotent stem cells, but it remains to be clarified whether myostatin is also involved in regulation of artificial differentiation of myoblasts from pluripotent stem cells. Here we show that the human induced pluripotent stem (iPS) cell-derived cells that were induced to differentiate into myoblasts expressed myostatin and its receptor during the differentiation. An addition of recombinant human myostatin (rhMyostatin) suppressed induction of MyoD and Myo5a, resulting in significant suppression of myoblast differentiation. The rhMyostatin treatment also inhibited proliferation of the cells at a later phase of differentiation. RNAi-mediated silencing of myostatin promoted differentiation of human iPS-derived embryoid body (EB) cells into myoblasts. These results strongly suggest that myostatin plays an important role in regulation of myoblast differentiation from iPS cells of human origin. The present findings also have significant implications for potential regenerative medicine for muscular diseases.

  6. Leukocyte-associated immunoglobulin-like receptor-1 is expressed on human megakaryocytes and negatively regulates the maturation of primary megakaryocytic progenitors and cell line

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Jiangnan, E-mail: xuejinagnan@263.net [Department of Immunology, Binzhou Medical University, Yantai 264003 (China); Zhang, Xiaoshu; Zhao, Haiya; Fu, Qiang; Cao, Yanning; Wang, Yuesi; Feng, Xiaoying; Fu, Aili [Department of Immunology, Binzhou Medical University, Yantai 264003 (China)

    2011-02-04

    Research highlights: {yields} LAIR-1 is expressed on human megakaryocytes from an early stage. {yields} Up-regulation of LAIR-1 negatively regulates megakaryocytic differentiation of cell line. {yields} LAIR-1 negatively regulates the differentiation of primary megakaryocytic progenitors. -- Abstract: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory collagen receptor which belongs to the immunoglobulin (Ig) superfamily. Although the inhibitory function of LAIR-1 has been extensively described in multiple leukocytes, its role in megakaryocyte (MK) has not been explored so far. Here, we show that LAIR-1 is expressed on human bone marrow CD34{sup +}CD41a{sup +} and CD41a{sup +}CD42b{sup +} cells. LAIR-1 is also detectable in a fraction of human cord blood CD34{sup +} cell-derived MK that has morphological characteristics of immature MK. In megakaryoblastic cell line Dami, the membrane protein expression of LAIR-1 is up-regulated significantly when cells are treated with phorbol ester phorbol 12-myristate 13-acetate (PMA). Furthermore, cross-linking of LAIR-1 in Dami cells with its natural ligand or anti-LAIR-1 antibody leads to the inhibition of cell proliferation and PMA-promoted differentiation when examined by the MK lineage-specific markers (CD41a and CD42b) and polyploidization. In addition, we also observed that cross-linking of LAIR-1 results in decreased MK generation from primary human CD34{sup +} cells cultured in a cytokines cocktail that contains TPO. These results suggest that LAIR-1 is a likely candidate for an early marker of MK differentiation, and provide initial evidence indicating that LAIR-1 serves as a negative regulator of megakaryocytopoiesis.

  7. Histological characteristics of human papilloma-virus-positive and -negative invasive and in situ squamous cell tumours of the penis

    DEFF Research Database (Denmark)

    Krustrup, Dorrit; Jensen, Helle Lone; van den Brule, Adriaan J C

    2009-01-01

    A high prevalence of cervical cancer associated high-risk types of human papillomavirus (hrHPV) has been demonstrated in premalignant and invasive squamous cell lesions of the penis, but large studies correlating histological characteristics with HPV status are few in number. Tumour tissues from...

  8. Anal and penile high-risk human papillomavirus prevalence in HIV-negative and HIV-infected MSM

    NARCIS (Netherlands)

    van Aar, Fleur; Mooij, Sofie H.; van der Sande, Marianne A. B.; Speksnijder, Arjen G. C. L.; Stolte, Ineke G.; Meijer, Chris J. L. M.; Verhagen, Dominique W. M.; King, Audrey J.; de Vries, Henry J. C.; Schim van der Loeff, Maarten F.

    2013-01-01

    Anal and penile high-risk human papillomavirus (HPV) infection is associated with anogenital cancer, which is especially common in HIV-infected MSM. We assessed HPV prevalence and determinants in MSM. Analysis of baseline data from a prospective cohort study. MSM aged 18 years or older were

  9. Human RNF169 is a negative regulator of the ubiquitin-dependent response to DNA double-strand breaks

    DEFF Research Database (Denmark)

    Poulsen, Maria; Lukas, Claudia; Lukas, Jiri

    2012-01-01

    Nonproteolytic ubiquitylation of chromatin surrounding deoxyribonucleic acid double-strand breaks (DSBs), mediated by the RNF8/RNF168 ubiquitin ligases, plays a key role in recruiting repair factors, including 53BP1 and BRCA1, to reestablish genome integrity. In this paper, we show that human RNF...

  10. Negative ... concord?

    NARCIS (Netherlands)

    Giannakidou, A

    The main claim of this paper is that a general theory of negative concord (NC) should allow for the possibility of NC involving scoping of a universal quantifier above negation. I propose that Greek NC instantiates this option. Greek n-words will be analyzed as polarity sensitive universal

  11. Subminimal negation

    NARCIS (Netherlands)

    Colacito, A.; de Jongh, D.; Vargas Sandoval, A.L.

    Minimal logic, i.e., intuitionistic logic without the ex falso principle, is investigated in its original form with a negation symbol instead of a symbol denoting the contradiction. A Kripke semantics is developed for minimal logic and its sublogics with a still weaker negation by introducing a

  12. Negative Leadership

    Science.gov (United States)

    2013-03-01

    Negative Leadership by Colonel David M. Oberlander United States Army United States Army War...SUBTITLE Negative Leadership 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Colonel David M...Dr. Richard C. Bullis Department of Command Leadership , and Management 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING

  13. Reducing the negative human-health impacts of bioenergy crop emissions through region-specific crop selection

    OpenAIRE

    Guenther, Alex; Lamarque, Jean-Francois; Barsanti, Kelley; Porter, William C.; Rosenstiel, Todd N.

    2015-01-01

    An expected global increase in bioenergy-crop cultivation as an alternative to fossil fuels will have consequences on both global climate and local air quality through changes in biogenic emissions of volatile organic compounds (VOCs). While greenhouse gas emissions may be reduced through the substitution of next-generation bioenergy crops such as eucalyptus, giant reed, and switchgrass for fossil fuels, the choice of species has important ramifications for human health, potentially reducing ...

  14. Anti-CD20 Monoclonal Antibody Treatment of Human Herpesvirus 8-Associated, Body Cavity-Based Lymphoma with an Unusual Phenotype in a Human Immunodeficiency Virus-Negative Patient

    Science.gov (United States)

    Pérez, Celeste L.; Rudoy, Silvia

    2001-01-01

    Human herpesvirus 8 (HHV-8), or Kaposi's sarcoma-associated herpesvirus, is a gammaherpesvirus first detected in Kaposi's sarcoma tumor cells and subsequently in primary effusion lymphoma (PEL) tumor cells and peripheral blood mononuclear cells from PEL patients. PEL has been recognized as an individual nosologic entity based on its distinctive features and consistent association with HHV-8 infection. PEL is an unusual form of body cavity-based B-cell lymphoma (BCBL). It occurs predominantly in human immunodeficiency virus (HIV)-positive patients but occasionally also in elderly HIV-negative patients. We describe a case of PEL, with ascites, bilateral pleural effusions, and a small axillary lymphadenopathy, in a 72-year-old HIV-negative man. PCR performed on a lymph node specimen and in liquid effusion was positive for HHV-8 and negative for Epstein-Barr virus. The immunophenotype of the neoplastic cells was B CD19+ CD20+ CD22+ with coexpression of CD10 and CD23 and with clonal kappa light chain rearrangement. The patient was treated with Rituximab, a chimeric (human-mouse) anti-CD20 monoclonal antibody. Thirteen months later, the patient continued in clinical remission. This is the first report of an HHV-8-associated BCBL in an HIV-negative patient in Argentina. PMID:11527816

  15. Correlation of LMP10 expression and clinical outcome in Human Papillomavirus (HPV positive and HPV-Negative tonsillar and base of tongue cancer.

    Directory of Open Access Journals (Sweden)

    Nikolaos Tertipis

    Full Text Available To examine LMP10 expression and its possible impact on clinical outcome in human papillomavirus (HPV positive and HPV-negative tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC.Outcome is better in HPV-positive TSCC and BOTSCC compared to matching HPV-negative tumours, with roughly 80% vs. 40% 5-year disease free survival (DFS with less aggressive treatment than today's chemoradiotherapy. Since current treatment often results in harmful side effects, less intensive therapy, with sustained patient survival would be an attractive alternative. However, other markers together with HPV status are necessary to select patients and for this purpose LMP10 expression is investigated here in parallel to HPV status and clinical outcome.From 385 patients diagnosed between 2000 and 2007 at the Karolinska University Hospital, 278 formalin fixed paraffin embedded TSCC and BOTSCC biopsies, with known HPV DNA status, were tested for LMP10 nuclear and cytoplasmic expression (fraction of positive cells and staining intensity. The data was then correlated to clinical outcome.An absent/low compared to a moderate/high LMP10 nuclear fraction of positive cells was correlated to a better 3-year DFS in the HPV-positive group of patients (log-rank p = 0.005, but not in the HPV-negative group. In the HPV-negative group of patients, in contrast to the HPV-positive group, moderate/high LMP10 cytoplasmic fraction and weak/moderate/high LMP10 cytoplasmic intensity correlated to a better 3-year DFS (p = 0.003 and p = 0.001 and 3-year overall survival (p = 0.001 and 0.009.LMP10 nuclear expression in the HPV-positive group and LMP10 cytoplasmic expression in the HPV-negative group of patients correlated to better clinical outcome.

  16. Correlation of LMP10 expression and clinical outcome in Human Papillomavirus (HPV) positive and HPV-Negative tonsillar and base of tongue cancer.

    Science.gov (United States)

    Tertipis, Nikolaos; Haeggblom, Linnea; Nordfors, Cecilia; Grün, Nathalie; Näsman, Anders; Vlastos, Andrea; Dalianis, Tina; Ramqvist, Torbjörn

    2014-01-01

    To examine LMP10 expression and its possible impact on clinical outcome in human papillomavirus (HPV) positive and HPV-negative tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC). Outcome is better in HPV-positive TSCC and BOTSCC compared to matching HPV-negative tumours, with roughly 80% vs. 40% 5-year disease free survival (DFS) with less aggressive treatment than today's chemoradiotherapy. Since current treatment often results in harmful side effects, less intensive therapy, with sustained patient survival would be an attractive alternative. However, other markers together with HPV status are necessary to select patients and for this purpose LMP10 expression is investigated here in parallel to HPV status and clinical outcome. From 385 patients diagnosed between 2000 and 2007 at the Karolinska University Hospital, 278 formalin fixed paraffin embedded TSCC and BOTSCC biopsies, with known HPV DNA status, were tested for LMP10 nuclear and cytoplasmic expression (fraction of positive cells and staining intensity). The data was then correlated to clinical outcome. An absent/low compared to a moderate/high LMP10 nuclear fraction of positive cells was correlated to a better 3-year DFS in the HPV-positive group of patients (log-rank p = 0.005), but not in the HPV-negative group. In the HPV-negative group of patients, in contrast to the HPV-positive group, moderate/high LMP10 cytoplasmic fraction and weak/moderate/high LMP10 cytoplasmic intensity correlated to a better 3-year DFS (p = 0.003 and p = 0.001) and 3-year overall survival (p = 0.001 and 0.009). LMP10 nuclear expression in the HPV-positive group and LMP10 cytoplasmic expression in the HPV-negative group of patients correlated to better clinical outcome.

  17. The epidemiology of human papillomavirus infection in HIV-positive and HIV-negative high-risk women in Kigali, Rwanda

    Directory of Open Access Journals (Sweden)

    Veldhuijzen Nienke J

    2011-12-01

    Full Text Available Abstract Background The prevalence, incidence and persistence of human papillomavirus (HPV types in sub-Saharan Africa are not well established. The objectives of the current study are to describe (predictors of the epidemiology of HPV among high-risk women in Kigali, Rwanda. Methods HIV-negative, high-risk women were seen quarterly for one year, and once in Year 2. HIV serostatus, clinical, and behavioral information were assessed at each visit, HPV types at Month 6 and Year 2, and other sexually transmitted infections (STI at selected visits. HPV prevalence was also assessed in HIV-positive, high-risk women. Results Prevalence of any HPV was 47.0% in HIV-negative women (median age 25 years compared to 72.2% in HIV-positive women (median age 27 years; OR 2.9, 95% CI 1.9-4.6. Among HIV-negative women, cumulative incidence of high-risk (HR-HPV was 28.0% and persistence 32.0% after a mean period of 16.6 and 16.9 months, respectively. Prior Chlamydia trachomatis and Neisseria gonorrhoeae infection, concurrent low-risk (LR-HPV infection and incident HSV-2 were associated with HR-HPV prevalence among HIV-negative women; prior C. trachomatis infection and co-infection with LR-HPV and HPV16-related HPV types with HR-HPV acquisition. HPV16-related types were the most prevalent and persistent. Conclusions High HPV prevalence, incidence and persistence were found among high-risk women in Kigali. HPV52 had the highest incidence; and, together with HPV33 and HPV58, were strongly associated with acquisition of other HR-HPV types in HIV-negative women.

  18. Arsenic induces functional re-expression of estrogen receptor α by demethylation of DNA in estrogen receptor-negative human breast cancer.

    Science.gov (United States)

    Du, Juan; Zhou, Nannan; Liu, Hongxia; Jiang, Fei; Wang, Yubang; Hu, Chunyan; Qi, Hong; Zhong, Caiyun; Wang, Xinru; Li, Zhong

    2012-01-01

    Estrogen receptor α (ERα) is a marker predictive for response of breast cancers to endocrine therapy. About 30% of breast cancers, however, are hormone- independent because of lack of ERα expression. New strategies are needed for re-expression of ERα and sensitization of ER-negative breast cancer cells to selective ER modulators. The present report shows that arsenic trioxide induces reactivated ERα, providing a target for therapy with ER antagonists. Exposure of ER-negative breast cancer cells to arsenic trioxide leads to re-expression of ERα mRNA and functional ERα protein in in vitro and in vivo. Luciferase reporter gene assays and 3-(4,5-dimethylthiazol-2-yl)- 5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays show that, upon exposure to arsenic trioxide, formerly unresponsive, ER-negative MDA-MB-231 breast cancer cells become responsive to ER antagonists, 4-hydroxytamoxifen and ICI 182,780. Furthermore, methylation- specific PCR and bisulfite-sequencing PCR assays show that arsenic trioxide induces partial demethylation of the ERα promoter. A methyl donor, S-adenosylmethionine (SAM), reduces the degree of arsenic trioxide-induced re-expression of ERα and demethylation. Moreover, Western blot and ChIP assays show that arsenic trioxide represses expression of DNMT1 and DNMT3a along with partial dissociation of DNMT1 from the ERα promoter. Thus, arsenic trioxide exhibits a previously undefined function which induces re-expression ERα in ER-negative breast cancer cells through demethylation of the ERα promoter. These findings could provide important information regarding the application of therapeutic agents targeting epigenetic changes in breast cancers and potential implication of arsenic trioxide as a new drug for the treatment of ER-negative human breast cancer.

  19. Arsenic induces functional re-expression of estrogen receptor α by demethylation of DNA in estrogen receptor-negative human breast cancer.

    Directory of Open Access Journals (Sweden)

    Juan Du

    Full Text Available Estrogen receptor α (ERα is a marker predictive for response of breast cancers to endocrine therapy. About 30% of breast cancers, however, are hormone- independent because of lack of ERα expression. New strategies are needed for re-expression of ERα and sensitization of ER-negative breast cancer cells to selective ER modulators. The present report shows that arsenic trioxide induces reactivated ERα, providing a target for therapy with ER antagonists. Exposure of ER-negative breast cancer cells to arsenic trioxide leads to re-expression of ERα mRNA and functional ERα protein in in vitro and in vivo. Luciferase reporter gene assays and 3-(4,5-dimethylthiazol-2-yl- 5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium (MTS assays show that, upon exposure to arsenic trioxide, formerly unresponsive, ER-negative MDA-MB-231 breast cancer cells become responsive to ER antagonists, 4-hydroxytamoxifen and ICI 182,780. Furthermore, methylation- specific PCR and bisulfite-sequencing PCR assays show that arsenic trioxide induces partial demethylation of the ERα promoter. A methyl donor, S-adenosylmethionine (SAM, reduces the degree of arsenic trioxide-induced re-expression of ERα and demethylation. Moreover, Western blot and ChIP assays show that arsenic trioxide represses expression of DNMT1 and DNMT3a along with partial dissociation of DNMT1 from the ERα promoter. Thus, arsenic trioxide exhibits a previously undefined function which induces re-expression ERα in ER-negative breast cancer cells through demethylation of the ERα promoter. These findings could provide important information regarding the application of therapeutic agents targeting epigenetic changes in breast cancers and potential implication of arsenic trioxide as a new drug for the treatment of ER-negative human breast cancer.

  20. Naringin inhibits growth potential of human triple-negative breast cancer cells by targeting β-catenin signaling pathway.

    Science.gov (United States)

    Li, Hongzhong; Yang, Bing; Huang, Jing; Xiang, Tingxiu; Yin, Xuedong; Wan, Jingyuan; Luo, Fuling; Zhang, Li; Li, Hongyuan; Ren, Guosheng

    2013-07-18

    Triple-negative (ER-/PR-/HER2-) breast cancer (TNBC) is a severe clinical problem because of its relatively poorer prognosis, aggressive behavior and lack of targeted therapies. Naringin, a major flavonoid extracted from citrus fruits, has been reported to exert promising anticancer activities. However, the detailed antitumor mechanism of naringin still remains enigmatic. In this study, TNBC cell lines-based in vitro and in vivo models were used to explore the anticancer effect and mechanism of naringin. Our data demonstrated that naringin inhibited cell proliferation, and promoted cell apoptosis and G1 cycle arrest, accompanied by increased p21 and decreased survivin. Meanwhile, β-catenin signaling pathway was found to be suppressed by naringin. In contrast, over-expressing β-catenin by adenoviral vector system in TNBC cells reversed the antitumor activity of naringin, and regulated p21 and survivin. Correspondingly, the antitumor potential of naringin was also observed in naringin-treated MDA-MB-231 xenograft mice, while immunohistochemical analysis of tumors from naringin-treated mice showed higher expression of p21 and lower expression of survivin and active β-catenin. Taken together, these results indicate that naringin could inhibit growth potential of TNBC cells by modulating β-catenin pathway, which suggests naringin might be used as a potential supplement for the prevention and treatment of breast cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Positive and negative regulation of cell proliferation by E2F-1: influence of protein level and human papillomavirus oncoproteins

    DEFF Research Database (Denmark)

    Melillo, R M; Helin, K; Lowy, D R

    1994-01-01

    that is defective for immortalization and binding of pRB and pRB-related proteins. By contrast, E2F-1 was unable to complement two other E7 mutants, p2PRO and p31/32ARG/PRO, which are also defective in the immortalization assay, although their proteins display wild-type binding of pRB in vitro. Since the binding...... levels of E2F-1, produced by transfection of the E2F-1 cDNA under the control of a strong promoter, reduced colony formation in normal human foreskin keratinocytes (NHFKs). This inhibition could not be overcome by wild-type human papillomavirus type 16 (HPV16) E6 and E7, two proteins which cooperate...... to immortalize NHFKs, or by a transdominant p53 mutant. High levels of E2F-1 also inhibited growth of primary and established fibroblasts. The growth-inhibitory activity required the DNA binding function of E2F-1 but not its transactivation or pRB binding activities. A positive role for lower levels of E2F-1...

  2. Tensin3 is a negative regulator of cell migration and all four Tensin family members are downregulated in human kidney cancer.

    Directory of Open Access Journals (Sweden)

    Danuta Martuszewska

    Full Text Available The Tensin family of intracellular proteins (Tensin1, -2, -3 and -4 are thought to act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Dysregulation of Tensin expression has previously been implicated in human cancer. Here, we have for the first time evaluated the significance of all four Tensins in a study of human renal cell carcinoma (RCC, as well as probed the biological function of Tensin3.Expression of Tensin2 and Tensin3 at mRNA and protein levels was largely absent in a panel of diverse human cancer cell lines. Quantitative RT-PCR analysis revealed mRNA expression of all four Tensin genes to be significantly downregulated in human kidney tumors (50-100% reduction versus normal kidney cortex; P<0.001. Furthermore, the mRNA expressions of Tensins mostly correlated positively with each other and negatively with tumor grade, but not tumor size. Immunohistochemical analysis revealed Tensin3 to be present in the cytoplasm of tubular epithelium in normal human kidney sections, whilst expression was weaker or absent in 41% of kidney tumors. A subset of tumor sections showed a preferential plasma membrane expression of Tensin3, which in clear cell RCC patients was correlated with longer survival. Stable expression of Tensin3 in HEK 293 cells markedly inhibited both cell migration and matrix invasion, a function independent of putative phosphatase activity in Tensin3. Conversely, siRNA knockdown of endogenous Tensin3 in human cancer cells significantly increased their migration.Our findings indicate that the Tensins may represent a novel group of metastasis suppressors in the kidney, the loss of which leads to greater tumor cell motility and consequent metastasis. Moreover, tumorigenesis in the human kidney may be facilitated by a general downregulation of Tensins. Therefore, anti-metastatic therapies may benefit from restoring or preserving Tensin expression in primary

  3. Comparison of Heterologous Prime-Boost Strategies against Human Immunodeficiency Virus Type 1 Gag Using Negative Stranded RNA Viruses.

    Science.gov (United States)

    Lawrence, Tessa M; Wanjalla, Celestine N; Gomme, Emily A; Wirblich, Christoph; Gatt, Anthony; Carnero, Elena; García-Sastre, Adolfo; Lyles, Douglas S; McGettigan, James P; Schnell, Matthias J

    2013-01-01

    This study analyzed a heterologous prime-boost vaccine approach against HIV-1 using three different antigenically unrelated negative-stranded viruses (NSV) expressing HIV-1 Gag as vaccine vectors: rabies virus (RABV), vesicular stomatitis virus (VSV) and Newcastle disease virus (NDV). We hypothesized that this approach would result in more robust cellular immune responses than those achieved with the use of any of the vaccines alone in a homologous prime-boost regimen. To this end, we primed BALB/c mice with each of the NSV-based vectors. Primed mice were rested for thirty-five days after which we administered a second immunization with the same or heterologous NSV-Gag viruses. The magnitude and quality of the Gag-specific CD8(+) T cells in response to these vectors post boost were measured. In addition, we performed challenge experiments using vaccinia virus expressing HIV-1 Gag (VV-Gag) thirty-three days after the boost inoculation. Our results showed that the choice of the vaccine used for priming was important for the detected Gag-specific CD8(+) T cell recall responses post boost and that NDV-Gag appeared to result in a more robust recall of CD8(+) T cell responses independent of the prime vaccine used. However, the different prime-boost strategies were not distinct for the parameters studied in the challenge experiments using VV-Gag but did indicate some benefits compared to single immunizations. Taken together, our data show that NSV vectors can individually stimulate HIV-Gag specific CD8(+) T cells that are effectively recalled by other NSV vectors in a heterologous prime-boost approach. These results provide evidence that RABV, VSV and NDV can be used in combination to develop vaccines needing prime-boost regimens to stimulate effective immune responses.

  4. Comparison of Heterologous Prime-Boost Strategies against Human Immunodeficiency Virus Type 1 Gag Using Negative Stranded RNA Viruses.

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    Tessa M Lawrence

    Full Text Available This study analyzed a heterologous prime-boost vaccine approach against HIV-1 using three different antigenically unrelated negative-stranded viruses (NSV expressing HIV-1 Gag as vaccine vectors: rabies virus (RABV, vesicular stomatitis virus (VSV and Newcastle disease virus (NDV. We hypothesized that this approach would result in more robust cellular immune responses than those achieved with the use of any of the vaccines alone in a homologous prime-boost regimen. To this end, we primed BALB/c mice with each of the NSV-based vectors. Primed mice were rested for thirty-five days after which we administered a second immunization with the same or heterologous NSV-Gag viruses. The magnitude and quality of the Gag-specific CD8(+ T cells in response to these vectors post boost were measured. In addition, we performed challenge experiments using vaccinia virus expressing HIV-1 Gag (VV-Gag thirty-three days after the boost inoculation. Our results showed that the choice of the vaccine used for priming was important for the detected Gag-specific CD8(+ T cell recall responses post boost and that NDV-Gag appeared to result in a more robust recall of CD8(+ T cell responses independent of the prime vaccine used. However, the different prime-boost strategies were not distinct for the parameters studied in the challenge experiments using VV-Gag but did indicate some benefits compared to single immunizations. Taken together, our data show that NSV vectors can individually stimulate HIV-Gag specific CD8(+ T cells that are effectively recalled by other NSV vectors in a heterologous prime-boost approach. These results provide evidence that RABV, VSV and NDV can be used in combination to develop vaccines needing prime-boost regimens to stimulate effective immune responses.

  5. Allogeneic Human Double Negative T Cells as a Novel Immunotherapy for Acute Myeloid Leukemia and Its Underlying Mechanisms.

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    Lee, JongBok; Minden, Mark D; Chen, Weihsu C; Streck, Elena; Chen, Branson; Kang, Hyeonjeong; Arruda, Andrea; Ly, Dalam; Der, Sandy D; Kang, Sohyeong; Achita, Paulina; D'Souza, Cheryl; Li, Yueyang; Childs, Richard W; Dick, John E; Zhang, Li

    2017-10-26

    Purpose: To explore the potential of ex vivo expanded healthy donor-derived allogeneic CD4 and CD8 double-negative cells (DNT) as a novel cellular immunotherapy for leukemia patients.Experimental Design: Clinical-grade DNTs from peripheral blood of healthy donors were expanded and their antileukemic activity and safety were examined using flow cytometry-based in vitro killing assays and xenograft models against AML patient blasts and healthy donor-derived hematopoietic cells. Mechanism of action was investigated using antibody-mediated blocking assays and recombinant protein treatment assays.Results: Expanded DNTs from healthy donors target a majority (36/46) of primary AML cells, including 9 chemotherapy-resistant patient samples in vitro, and significantly reduce the leukemia load in patient-derived xenograft models in a DNT donor-unrestricted manner. Importantly, allogeneic DNTs do not attack normal hematopoietic cells or affect hematopoietic stem/progenitor cell engraftment and differentiation, or cause xenogeneic GVHD in recipients. Mechanistically, DNTs express high levels of NKG2D and DNAM-1 that bind to cognate ligands preferentially expressed on AML cells. Upon recognition of AML cells, DNTs rapidly release IFNγ, which further increases NKG2D and DNAM-1 ligands' expression on AML cells. IFNγ pretreatment enhances the susceptibility of AML cells to DNT-mediated cytotoxicity, including primary AML samples that are otherwise resistant to DNTs, and the effect of IFNγ treatment is abrogated by NKG2D and DNAM-1-blocking antibodies.Conclusions: This study supports healthy donor-derived allogeneic DNTs as a therapy to treat patients with chemotherapy-resistant AML and also reveals interrelated roles of NKG2D, DNAM-1, and IFNγ in selective targeting of AML by DNTs. Clin Cancer Res; 1-13. ©2017 AACR. ©2017 American Association for Cancer Research.

  6. GTP-bound Rab3A exhibits consecutive positive and negative roles during human sperm dense-core granule exocytosis.

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    Bustos, Matías A; Roggero, Carlos M; De la Iglesia, Paola X; Mayorga, Luis S; Tomes, Claudia N

    2014-08-01

    Exocytosis of mammalian sperm dense-core secretory granule relies on the same fusion molecules as all other secretory cells; one such molecule is the small GTPase Rab3A. Here, we report an in-depth biochemical characterization of the role of Rab3A in secretion by scrutinizing the exocytotic response of streptolysin O-permeabilized human sperm to the acute application of a number of Rab3A-containing constructs and correlating the findings with those gathered with the endogenous protein. Full length, geranylgeranylated, and active Rab3A elicited human sperm exocytosis per se. With Rab3A/Rab22A chimeric proteins, we demonstrated that the carboxy-terminal domain of the Rab3A molecule was necessary and sufficient to promote exocytosis, whereas its amino-terminus prevented calcium-triggered secretion. Interestingly, full length Rab3A halted secretion when added after the docking of the acrosome to the plasma membrane. This effect depended on the inability of Rab3A to hydrolyze GTP. We combined modified immunofluorescence and acrosomal staining protocols to detect membrane fusion and the activation status of endogenous Rab3 simultaneously in individual cells, and found that GTP hydrolysis on endogenous Rab3 was mandatory for fusion pores to open. Our findings contribute to establishing that Rab3 modulates regulated exocytosis differently depending on the nucleotide bound and the exocytosis stage under study. © The Author (2014). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

  7. Diffuse glomerular nodular lesions in diabetic pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha, an inheritant diabetic gene in humans.

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    Satoshi Hara

    Full Text Available Glomerular nodular lesions, known as Kimmelstiel-Wilson nodules, are a pathological hallmark of progressive human diabetic nephropathy. We have induced severe diabetes in pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha (HNF1α P291fsinsC, a maturity-onset diabetes of the young type-3 (MODY3 gene in humans. In this model, glomerular pathology revealed that formation of diffuse glomerular nodules commenced as young as 1 month of age and increased in size and incidence until the age of 10 months, the end of the study period. Immunohistochemistry showed that the nodules consisted of various collagen types (I, III, IV, V and VI with advanced glycation end-product (AGE and Nε-carboxymethyl-lysine (CML deposition, similar to those in human diabetic nodules, except for collagen type I. Transforming growth factor-beta (TGF-β was also expressed exclusively in the nodules. The ultrastructure of the nodules comprised predominant interstitial-type collagen deposition arising from the mesangial matrices. Curiously, these nodules were found predominantly in the deep cortex. However, diabetic pigs failed to show any of the features characteristic of human diabetic nephropathy; e.g., proteinuria, glomerular basement membrane thickening, exudative lesions, mesangiolysis, tubular atrophy, interstitial fibrosis, and vascular hyalinosis. The pigs showed only Armanni-Ebstein lesions, a characteristic tubular manifestation in human diabetes. RT-PCR analysis showed that glomeruli in wild-type pigs did not express endogenous HNF1α and HNF1β, indicating that mutant HNF1α did not directly contribute to glomerular nodular formation in diabetic pigs. In conclusion, pigs harboring the dominant-negative mutant human MODY3 gene showed reproducible and distinct glomerular nodules, possibly due to AGE- and CML-based collagen accumulation. Although the pathology differed in several respects from that of human glomerular nodular lesions, the

  8. Gram-positive and gram-negative bacteria induce different patterns of cytokine production in human mononuclear cells irrespective of taxonomic relatedness.

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    Skovbjerg, Susann; Martner, Anna; Hynsjö, Lars; Hessle, Christina; Olsen, Ingar; Dewhirst, Floyd E; Tham, Wilhelm; Wold, Agnes E

    2010-01-01

    Upon bacterial stimulation, tissue macrophages produce a variety of cytokines that orchestrate the immune response that clears the infection. We have shown that Gram-positives induce higher levels of interleukin-12 (IL-12), interferon-gamma (IFN-gamma), and tumor necrosis factor (TNF) from human peripheral blood mononuclear cells (PBMCs) than do Gram-negatives, which instead induce more of IL-6, IL-8, and IL-10. Here, we study whether these patterns follows or crosses taxonomic borders. PBMCs from blood donors were incubated with UV-inactivated bacteria representing 37 species from five phyla. IL-12, TNF, IL-1beta, IL-6, IL-8, and IL-10 were measured in the supernatants after 24 h and IFN-gamma after 5 days. Irrespective of phylogenetic position, Gram-positive bacteria induced much more IL-12 (nine times more on average) and IFN-gamma (seven times), more TNF (three times), and slightly more IL-1beta (1.5 times) than did Gram-negatives, which instead induced more IL-6 (1.5 times), IL-8 (1.9 times), and IL-10 (3.3 times) than did Gram-positives. A notable exception was the Gram-positive Listeria monocytogenes, which induced very little IL-12, IFN-gamma, and TNF. The results confirm the fundamental difference in innate immune responses to Gram-positive and Gram-negative bacteria, which crosses taxonomic borders and probably reflects differences in cell wall structure.

  9. Human papillomavirus 16 (HPV16 enhances tumor growth and cancer stemness of HPV-negative oral/oropharyngeal squamous cell carcinoma cells via miR-181 regulation

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    Sung Hee Lee

    2015-12-01

    Full Text Available High-risk human papillomaviruses (e. g., HPV16, HPV18 are closely associated with the development of head and neck cancers including oral/oropharyngeal squamous cell carcinoma (OSCC. We previously demonstrated immortalization of normal human oral keratinocytes by introducing high-risk HPV whole genome, suggesting that HPV infection plays an important role in the early stage of oral carcinogenesis. Although HPV infection may occur in different stages of cancer development, roles of HPV in exacerbating malignant phenotypes in already-transformed cells in the context of cancer stemness are not clearly defined. In this study, we investigated the role of HPV16 in promoting the virulence of HPV-negative OSCC. Introducing HPV16 whole genome in HPV-negative OSCC increased malignant growth and self-renewal capacity, a key characteristic of cancer stem cells (CSCs. HPV16 also enhanced other CSC properties, including aldehyde dehydrogenase 1 (ALDH1 activity, migration/invasion, and CSC-related factor expression. Mechanistically, we found that HPV16 inhibited the expression of miR-181a and miR-181d (miR-181a/d at the transcriptional level. Ectopic expression of miR-181a/d decreased anchorage independent growth and CSC phenotype of HPV16-transfected OSCC. Furthermore, silencing of miR-181a/d target genes, i. e., K-ras and ALDH1, abrogated the effects of HPV16 in HPV16-transfected OSCC, supporting the functional importance of HPV16/miR-181a/d axis in HPV-mediated oral carcinogenesis. Our study suggests that high-risk HPV infection further promotes malignancy in HPV-negative OSCC by enhancing cancer stemness via miR-181a/d regulation. Consequently, miR-181a/d may represent a novel therapeutic agent for the treatment of HPV-positive OSCC. Keywords: HPV, OSCC, cancer stem cells, miR-181

  10. TRAIL-R1 is a negative regulator of pro-inflammatory responses and modulates long-term sequelae resulting from Chlamydia trachomatis infections in humans.

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    Mufadhal Al-Kuhlani

    Full Text Available The immune system eliminates Chlamydia trachomatis infection through inflammation. However, uncontrolled inflammation can enhance pathology. In mice, TNF-related apoptosis-inducing ligand receptor (TRAIL-R, known for its effects on apoptosis, also regulates inflammation. In humans, the four homologues of TRAIL-R had never been investigated for effects on inflammation. Here, we examined whether TRAIL-R regulates inflammation during chlamydial infection. We examined TRAIL-R1 single nucleotide polymorphisms (SNPs in an Ecuadorian cohort with and without C. trachomatis infections. There was a highly significant association for the TRAIL+626 homozygous mutant GG for infection vs no infection in this population. To confirm the results observed in the human population, primary lung fibroblasts and bone marrow-derived macrophages (BMDMs were isolated from wildtype (WT and TRAIL-R-deficient mice, and TRAIL-R1 levels in human cervical epithelial cells were depleted by RNA interference. Infection of BMDMs and primary lung fibroblasts with C. trachomatis strain L2, or the murine pathogen C. muridarum, led to higher levels of MIP2 mRNA expression or IL-1β secretion from TRAIL-R-deficient cells than WT cells. Similarly, depletion of TRAIL-R1 expression in human epithelial cells resulted in a higher level of IL-8 mRNA expression and protein secretion during C. trachomatis infection. We conclude that human TRAIL-R1 SNPs and murine TRAIL-R modulate the innate immune response against chlamydial infection. This is the first evidence that human TRAIL-R1 is a negative regulator of inflammation and plays a role in modulating Chlamydia pathogenesis.

  11. Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.

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    Ailin Lepletier

    2014-10-01

    Full Text Available The protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironmental and lymphoid compartments. Acute infection results in severe atrophy of the organ and early release of immature thymocytes into the periphery. To date, the pathophysiological effects of thymic changes promoted by parasite-inducing premature release of thymocytes to the periphery has remained elusive. Herein, we show that sphingosine-1-phosphate (S1P, a potent mediator of T cell chemotaxis, plays a role in the exit of immature double-negative thymocytes in experimental Chagas disease. In thymuses from T. cruzi-infected mice we detected reduced transcription of the S1P kinase 1 and 2 genes related to S1P biosynthesis, together with increased transcription of the SGPL1 sphingosine-1-lyase gene, whose product inactivates S1P. These changes were associated with reduced intrathymic levels of S1P kinase activity. Interestingly, double-negative thymocytes from infected animals expressed high levels of the S1P receptor during infection, and migrated to lower levels of S1P. Moreover, during T. cruzi infection, this thymocyte subset expresses high levels of IL-17 and TNF-α cytokines upon polyclonal stimulation. In vivo treatment with the S1P receptor antagonist FTY720 resulted in recovery the numbers of double-negative thymocytes in infected thymuses to physiological levels. Finally, we showed increased numbers of double-negative T cells in the peripheral blood in severe cardiac forms of human Chagas disease.

  12. Impact of age on the false negative rate of human papillomavirus DNA test in patients with atypical squamous cells of undetermined significance.

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    Won, Kyu-Hee; Lee, Jae Yeon; Cho, Hye-Yon; Suh, Dong Hoon; No, Jae Hong; Kim, Yong-Beom

    2015-03-01

    Human papillomavirus (HPV) test was incorporated into the triage of lesser abnormal cervical cytologies: atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL). This study aimed to evaluate the impact of age on the efficacy of HPV testing in patients with lesser abnormal cervical cytologies. A total of 439 patients with ASCUS or LSIL were included. The association between age groups and the diagnostic performances of HPV test for high-grade cervical intraepithelial neoplasia (CIN2+) was evaluated. Median age was 44 years (range, 17 to 75 years). ASCUS was more frequently observed in older patients while LSIL was more common in younger patients (P=0.002). CIN2+ was found in 11.3% (32/284) of the ASCUS patients and 12.9% (20/155) of patients with LSIL. Older patients with ASCUS showed lower HPV infection rates (P=0.025), but not LSIL (P=0.114). However, the prevalence of CIN2+ was similar between the age groups with ASCUS or LSIL. In patients with ASCUS, the false negative rate of HPV test for CIN2+ was 6.2%. The false negative rate of the HPV test became higher with increasing of the age after the age of 50 (P=0.034). Our findings suggest that false negative rate of the HPV test for CIN2+ in ASCUS patients older than 50 years might become higher with increasing of the age. Negative HPV results in patients of the age >50 years with ASCUS should be carefully interpreted.

  13. Equol as a potent radiosensitizer in estrogen receptor-positive and -negative human breast cancer cell lines.

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    Taghizadeh, Bita; Ghavami, Laleh; Nikoofar, Alireza; Goliaei, Bahram

    2015-07-01

    Breast cancer is the most common cause of cancer death among women worldwide, and diet plays an important role in its prevention and progression. Radiotherapy has a limited but important role in the management of nearly every stage of breast cancer. We studied whether equol, the major metabolite of the soybean isoflavone daidzein, could enhance radiosensitivity in two human breast cancer cell lines (T47D and MDA-MB-231). MTT assay was used to examine equol's effect on cell viability. Sensitivity of cells to equol, radiation and a combination of both was determined by colonogenic assays. Induction of apoptosis by equol, radiation and the combination of both was also determined by acridine orange/ethidium bromide double staining fluorescence microscopy. DNA strand breaks were assessed by Comet assay. MTT assay showed that equol (0.1-350 μM) inhibited MDA-MB-231 and T47D cell growth in a time- and dose-dependent manner. Treatment of cells with equol for 72 h (MDA-MB-231) and 24 h (T47D) was found to inhibit cell growth with IC50 values of 252 μM and 228 μM, respectively. Furthermore, pretreatment of cells with 50 μM equol for 72 h (MDA-MB-231) and 24 h (T47D) sensitized the cells to irradiation. Equol was also found to enhance radiation-induced apoptosis. Comet assay results showed that the radiosensitizing effect of equol was accompanied by increased radiation-induced DNA damages. These results suggest for the first time that equol can be considered as a radiosensitizing agent and its effects may be due to increasing cell death following irradiation, increasing the remaining radiation-induced DNA damage and thus reducing the surviving fraction of irradiated cells.

  14. Human and Murine IFIT1 Proteins Do Not Restrict Infection of Negative-Sense RNA Viruses of the Orthomyxoviridae, Bunyaviridae, and Filoviridae Families

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    Pinto, Amelia K.; Williams, Graham D.; Szretter, Kristy J.; White, James P.; Proença-Módena, José Luiz; Liu, Gai; Olejnik, Judith; Brien, James D.; Ebihara, Hideki; Mühlberger, Elke; Amarasinghe, Gaya; Diamond, Michael S.; Boon, Adrianus C. M.; Doms, R. W.

    2015-07-08

    Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) is a host protein with reported cell-intrinsic antiviral activity against several RNA viruses. The proposed basis for the activity against negative-sense RNA viruses is the binding to exposed 5'-triphosphates (5'-ppp) on the genome of viral RNA. However, recent studies reported relatively low binding affinities of IFIT1 for 5'-ppp RNA, suggesting that IFIT1 may not interact efficiently with this moiety under physiological conditions. To evaluate the ability of IFIT1 to have an impact on negative-sense RNA viruses, we infectedIfit1-/-and wild-type control mice and primary cells with four negative-sense RNA viruses (influenza A virus [IAV], La Crosse virus [LACV], Oropouche virus [OROV], and Ebola virus) corresponding to three distinct families. Unexpectedly, a lack ofIfit1gene expression did not result in increased infection by any of these viruses in cell culture. Analogously, morbidity, mortality, and viral burdens in tissues were identical betweenIfit1-/-and control mice after infection with IAV, LACV, or OROV. Finally, deletion of the human IFIT1 protein in A549 cells did not affect IAV replication or infection, and reciprocally, ectopic expression of IFIT1 in HEK293T cells did not inhibit IAV infection. To explain the lack of antiviral activity against IAV, we measured the binding affinity of IFIT1 for RNA oligonucleotides resembling the 5' ends of IAV gene segments. The affinity for 5'-ppp RNA was approximately 10-fold lower than that for non-2'-O-methylated (cap 0) RNA oligonucleotides. Based on this analysis, we conclude that IFIT1 is not a dominant restriction factor against negative-sense RNA viruses.

    IMPORTANCENegative-sense RNA viruses, including influenza virus and Ebola virus, have been responsible for some of the most deadly outbreaks in recent

  15. UVB induces a genome-wide acting negative regulatory mechanism that operates at the level of transcription initiation in human cells.

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    Akos Gyenis

    2014-07-01

    Full Text Available Faithful transcription of DNA is constantly threatened by different endogenous and environmental genotoxic effects. Transcription coupled repair (TCR has been described to stop transcription and quickly remove DNA lesions from the transcribed strand of active genes, permitting rapid resumption of blocked transcription. This repair mechanism has been well characterized in the past using individual target genes. Moreover, numerous efforts investigated the fate of blocked RNA polymerase II (Pol II during DNA repair mechanisms and suggested that stopped Pol II complexes can either backtrack, be removed and degraded or bypass the lesions to allow TCR. We investigated the effect of a non-lethal dose of UVB on global DNA-bound Pol II distribution in human cells. We found that the used UVB dose did not induce Pol II degradation however surprisingly at about 93% of the promoters of all expressed genes Pol II occupancy was seriously reduced 2-4 hours following UVB irradiation. The presence of Pol II at these cleared promoters was restored 5-6 hours after irradiation, indicating that the negative regulation is very dynamic. We also identified a small set of genes (including several p53 regulated genes, where the UVB-induced Pol II clearing did not operate. Interestingly, at promoters, where Pol II promoter clearance occurs, TFIIH, but not TBP, follows the behavior of Pol II, suggesting that at these genes upon UVB treatment TFIIH is sequestered for DNA repair by the TCR machinery. In agreement, in cells where the TCR factor, the Cockayne Syndrome B protein, was depleted UVB did not induce Pol II and TFIIH clearance at promoters. Thus, our study reveals a UVB induced negative regulatory mechanism that targets Pol II transcription initiation on the large majority of transcribed gene promoters, and a small subset of genes, where Pol II escapes this negative regulation.

  16. Prevalence and risk factors of anal human papillomavirus infection among HIV-negative men who have sex with men in Urumqi city of Xinjiang Uyghur Autonomous Region, China.

    Science.gov (United States)

    Tian, Tian; Mijiti, Peierdun; Bingxue, Huang; Fadong, Zhang; Ainiwaer, Abidan; Guoyao, Sang; Zhanlin, Zhang; Mahan, Yeledan; Xiaoqin, Tuo; Zheng, Gong; Jianghong, Dai

    2017-01-01

    Infection with human papillomavirus (HPV) is the most common sexually transmitted infection among men who have sex with men (MSM). Study on prevalence and risk factors of anal HPV infection among HIV-negative MSM in Northwestern China was rare. We performed a cross-sectional study of HPV prevalence using anal swab specimens among HIV-negative MSM in Urumqi city of Xinjiang Uyghur Autonomous Region, China between April 1st and October 30th in 2016. Prevalence of any anal HPV infection, high-risk and low-risk HPV infection was estimated. Risk factors associated with any anal HPV infection was analyzed using univariate and multivariate logistic regression models. Among 538 potential participants, 500(92.9%) were recruited in this study. The genotyping results of anal HPV infection were available for all. Of them, 259 (51.8%), 190 (38.0%) and 141(28.2%) were positive for at least one of the targeted 37 HPV genotypes, high-risk HPV genotypes, and any low-risk HPV genotypes. The most prevalent anal HPV genotype was HPV 6(11.8%), followed by HPV 16(11.2%), HPV 11(10.8%), HPV 51(7.0%) and HPV 18(5.4%).Among those infected with at least one of the targeted 37 anal HPV genotypes, 75(29.0%), 155(59.8%) and 191(73.7%) were infected with 2-valent, quadrivalent and 9-valent HPV vaccine-covered genotypes. Receptive anal intercourse in the past year was the only predictor of any anal HPV infection in multivariate logistic regression model. Prevalence of any anal HPV infection and high-risk HPV infection among HIV-negative MSM in Urumqi city of Xinjiang is high. The majority of genotypes detected in our study were covered by quadrivalent and 9-valent HPV vaccines. Regular anal exams and early HPV vaccination among MSM may be considered in future HPV prevention programs in Xinjiang, China.

  17. Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

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    Abdel-Razeq H

    2016-10-01

    Full Text Available Hikmat Abdel-RazeqDepartment of Internal Medicine, King Hussein Cancer Center, Amman, JordanI read with great interest the review written elegantly by Gradishar addressing the challenges that community oncologists face in treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor-2 (HER2-negative advanced breast cancer in your journal.1As the author correctly stated, resistance to endocrine therapy in women with hormone receptor-positive disease is very frequent and almost inevitable.Understanding the multiple known mechanisms for endocrine resistance has helped physicians and researchers target these pathways.2 Many of the recently introduced drugs, such as the mTOR inhibitor everolimus3 and the cyclin-dependent kinase (CDK 4/6 inhibitor palbociclib,4 are in clinical practice and have been already incorporated in international guidelines.5View original paper by Gradishar.

  18. Prevalence of enteric protozoa in human immunodeficiency virus (HIV)-positive and HIV-negative men who have sex with men from Sydney, Australia.

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    Stark, Damien; Fotedar, Rashmi; van Hal, Sebastian; Beebe, Nigel; Marriott, Deborah; Ellis, John T; Harkness, John

    2007-03-01

    A prospective, comparative study of the prevalence of enteric protozoa was determined among human immunodeficiency virus (HIV)- positive and HIV-negative men who have sex with men (MSM) in Sydney, Australia. A total of 1,868 patients submitted stool specimens; 1,246 were from MSM (628 HIV positive and 618 HIV positive) and 622 from non-MSM were examined over a 36-month period. A total of 651 (52.2%) stool specimens from MSM were positive for protozoa compared with 85 (13%) from non-MSM. There was a significant difference in the prevalence of Blastocystis hominis, Endolimax nana, Entamoeba histolytica/dispar complex, Entamoeba hartmanni, Iodamoeba butschlii, and Enteromonas hominis detected between MSM and non-MSM (P<0.001). The only notable difference between HIV-negative and HIV-positive MSM was that HIV-infected MSM were found to more likely have a Cryptosporidium parvum infection. Entamoeba histolytica was found in 3 patients, E. dispar in 25, and E. moshkovskii in 17, all of whom were MSM. When compared with a control group, MSM were significantly more likely to harbor intestinal protozoa and have multiple parasites present. The results of this study show high rates of enteric parasites persist in MSM and highlight the importance of testing for intestinal parasites in MSM. This is the first report of E. moshkovskii from MSM.

  19. Study of clinical profile of herpes zoster in human immunodeficiency virus positive and negative patients at a rural-based tertiary care center, Gujarat.

    Science.gov (United States)

    Vora, Rita V; Anjaneyan, Gopikrishnan; Kota, Rahul Krishna S; Pilani, Abhishek P; Diwan, Nilofar G; Patel, Nidhi N

    2017-01-01

    Herpes zoster usually presents with typically grouped vesicles on erythematous base involving single dermatome with self-limiting nature in immunocompetent individuals while it may present in extensive form involving multiple dermatomes involvement or disseminated form in immunocompromised, especially in human immunodeficiency virus (HIV). The aim of this study was to study the prevalence of HIV in patients of herpes zoster, to compare the clinical presentation of herpes zoster in HIV-infected and noninfected patient. The study was carried out in the Department of Dermatology in a Teaching Institute of Gujarat, from June 2008 to May 2014 after ethical clearance. The study population included all the patients with a clinical diagnosis of herpes zoster. All the patients were investigated for HIV infection after written consent. Out of total 688 patients of herpes zoster, 35 (5.1%) were HIV-positive, 26 (74.3%) were males and 9 (25.7%) were females. Among HIV-positive patients, 29 (82.85%) patients had localized dermatomal involvement, 4 (11.42%) patients had multiple dermatomal involvement, and only 2 (5.71%) had disseminated zoster while among HIV-negative, 636 (97.40%) had localized dermatomal involvement, 14 (2.14%) patients had multiple dermatomal involvement, and 3 (0.45%) had disseminated zoster. Cervical dermatome was most commonly involved dermatome in patients of HIV. Disseminated and multiple dermatomal involvement was more commonly involved among HIV-positive patients when compared to HIV-negative patients.

  20. The human being's spiritual experiences in a mental healthcare context; their positive and negative meaning and impact on health--a hermeneutic approach.

    Science.gov (United States)

    Koslander, Tiburtius; Lindström, Unni Å; Barbosa da Silva, António

    2013-09-01

    The study aims at describing different meanings of patients' spiritual experiences and their impact on patients' health in mental healthcare. The different contents of patients' spiritual experiences are often understood by caregivers as the expressions of patients' religious speculation. The study has a hermeneutic approach, inspired by Gadamer. Its theoretical pre-understanding is Caring Science perspective, according to which the human being is a unity of body, psyche and spirit. The sources are 32 stories selected from William James' book (1956) The Varieties of Religious Experience. They are hermeneutically interpreted and discussed in the light of international research on patients' spirituality to gain a deeper understanding. The results are three main themes: (i) the positive meanings of spirituality, (ii) the negative meanings of spirituality and (iii) the both negative and positive meaning of spirituality. Therefore, it is a very important task for mental caregivers to address patients' spiritual dimension to help them adequately. © 2012 The Authors. Scandinavian Journal of Caring Sciences © 2012 Nordic College of Caring Science.

  1. Immunoregulatory mechanisms and CD4-CD8- (double negative) T cell subpopulations in human cutaneous leishmaniasis: a balancing act between protection and pathology

    Science.gov (United States)

    Gollob, Kenneth J.; Antonelli, Lis R. V.; Faria, Daniela R.; Keesen, Tatjana S.L.; Dutra, Walderez O.

    2013-01-01

    Cellular immune responses directed against protozoan parasites are key for controlling pathogen replication and disease resolution. However, an uncontrolled, or improperly controlled, response can be deleterious to the host in terms of both allowing for the establishment of pathology, as well as less effective establishment of memory responses. Human cutaneous leishmaniasis is a disease caused by the infection with Leishmania spp. following a bite from the sandfly, the natural vector of this disease. Tens of millions worldwide are currently infected with Leishmania and no effective vaccines have been developed to date. In the face of the complexity presented by the interaction between a host (humans) with the parasite, Leishmania, and the fact that this parasite is inoculated by another complex, biologically active, vector, the sandfly, it is clearly important to study the immunoregulatory mechanisms that are induced in humans naturally infected by this parasite if we hope to develop effective vaccines and immunotherapeutic treatments in the future. Our laboratory has focused over the years on the study of the local and systemic T cell response during the first episode of cutaneous leishmaniasis suffered by individuals before they undergo antimony treatment. The goal of this review is to briefly outline our findings with hopes of putting our most recent studies concerning the dichotomy between alpha/beta TCR and gamma/delta TCR expressing, CD4- CD8- (double negative-DN) T cells in the context of a balanced immune response against Leishmania and to discuss the implications of these findings toward our understanding of human leishmaniasis. PMID:18687296

  2. Human Colon Tumors Express a Dominant-Negative Form of SIGIRR That Promotes Inflammation and Colitis-Associated Colon Cancer in Mice.

    Science.gov (United States)

    Zhao, Junjie; Bulek, Katarzyna; Gulen, Muhammet F; Zepp, Jarod A; Karagkounis, Georgio; Martin, Bradley N; Zhou, Hao; Yu, Minjia; Liu, Xiuli; Huang, Emina; Fox, Paul L; Kalady, Matthew F; Markowitz, Sanford D; Li, Xiaoxia

    2015-12-01

    Single immunoglobulin and toll-interleukin 1 receptor (SIGIRR), a negative regulator of the Toll-like and interleukin-1 receptor (IL-1R) signaling pathways, controls intestinal inflammation and suppresses colon tumorigenesis in mice. However, the importance of SIGIRR in human colorectal cancer development has not been determined. We investigated the role of SIGIRR in development of human colorectal cancer. We performed RNA sequence analyses of pairs of colon tumor and nontumor tissues, each collected from 68 patients. Immunoblot and immunofluorescence analyses were used to determine levels of SIGIRR protein in primary human colonic epithelial cells, tumor tissues, and colon cancer cell lines. We expressed SIGIRR and mutant forms of the protein in Vaco cell lines. We created and analyzed mice that expressed full-length (control) or a mutant form of Sigirr (encoding SIGIRR(N86/102S), which is not glycosylated) specifically in the intestinal epithelium. Some mice were given azoxymethane (AOM) and dextran sulfate sodium to induce colitis-associated cancer. Intestinal tissues were collected and analyzed by immunohistochemical and gene expression profile analyses. RNA sequence analyses revealed increased expression of a SIGIRR mRNA isoform, SIGIRR(ΔE8), in colorectal cancer tissues compared to paired nontumor tissues. SIGIRR(ΔE8) is not modified by complex glycans and is therefore retained in the cytoplasm-it cannot localize to the cell membrane or reduce IL1R signaling. SIGIRR(ΔE8) interacts with and has a dominant-negative effect on SIGIRR, reducing its glycosylation, localization to the cell surface, and function. Most SIGIRR detected in human colon cancer tissues was cytoplasmic, whereas in nontumor tissues it was found at the cell membrane. Mice that expressed SIGIRR(N86/102S) developed more inflammation and formed larger tumors after administration of azoxymethane and dextran sulfate sodium than control mice; colon tissues from these mutant mice expressed

  3. Human Leukocyte Antigen (HLA Class I Down-Regulation by Human Immunodeficiency Virus Type 1 Negative Factor (HIV-1 Nef: What Might We Learn From Natural Sequence Variants?

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    Philip Mwimanzi

    2012-09-01

    Full Text Available HIV-1 causes a chronic infection in humans that is characterized by high plasma viremia, progressive loss of CD4+ T lymphocytes, and severe immunodeficiency resulting in opportunistic disease and AIDS. Viral persistence is mediated in part by the ability of the Nef protein to down-regulate HLA molecules on the infected cell surface, thereby allowing HIV-1 to evade recognition by antiviral CD8+ T lymphocytes. Extensive research has been conducted on Nef to determine protein domains that are required for its immune evasion activities and to identify critical cellular co-factors, and our mechanistic understanding of this process is becoming more complete. This review highlights our current knowledge of Nef-mediated HLA class I down-regulation and places this work in the context of naturally occurring sequence variation in this protein. We argue that efforts to fully understand the critical role of Nef for HIV-1 pathogenesis will require greater analysis of patient-derived sequences to elucidate subtle differences in immune evasion activity that may alter clinical outcome.

  4. The Negative Repetition Effect

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    Mulligan, Neil W.; Peterson, Daniel J.

    2013-01-01

    A fundamental property of human memory is that repetition enhances memory. Peterson and Mulligan (2012) recently documented a surprising "negative repetition effect," in which participants who studied a list of cue-target pairs twice recalled fewer targets than a group who studied the pairs only once. Words within a pair rhymed, and…

  5. Identification of Potential Glycoprotein Biomarkers in Estrogen Receptor Positive (ER+ and Negative (ER- Human Breast Cancer Tissues by LC-LTQ/FT-ICR Mass Spectrometry

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    Suzan M. Semaan, Xu Wang, Alan G. Marshall, Qing-Xiang Amy Sang

    2012-01-01

    Full Text Available Breast cancer is the second most fatal cancer in American women. To increase the life expectancy of patients with breast cancer new diagnostic and prognostic biomarkers and drug targets must be identified. A change in the glycosylation on a glycoprotein often causes a change in the function of that glycoprotein; such a phenomenon is correlated with cancerous transformation. Thus, glycoproteins in human breast cancer estrogen receptor positive (ER+ tissues and those in the more advanced stage of breast cancer, estrogen receptor negative (ER- tissues, were compared. Glycoproteins showing differences in glycosylation were examined by 2-dimensional gel electrophoresis with double staining (glyco- and total protein staining and identified by reversed-phase nano-liquid chromatography coupled with a hybrid linear quadrupole ion trap/ Fourier transform ion cyclotron resonance mass spectrometer. Among the identified glycosylated proteins are alpha 1 acid glycoprotein, alpha-1-antitrypsin, calmodulin, and superoxide dismutase mitochondrial precursor that were further verified by Western blotting for both ER+ and ER- human breast tissues. Results show the presence of a possible glycosylation difference in alpha-1-antitrypsin, a potential tumor-derived biomarker for breast cancer progression, which was expressed highest in the ER- samples.

  6. Decreased BECN1 mRNA Expression in Human Breast Cancer is Associated With Estrogen Receptor-Negative Subtypes and Poor Prognosis

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    Hao Tang

    2015-03-01

    Full Text Available Both BRCA1 and Beclin 1 (BECN1 are tumor suppressor genes, which are in close proximity on the human chromosome 17q21 breast cancer tumor susceptibility locus and are often concurrently deleted. However, their importance in sporadic human breast cancer is not known. To interrogate the effects of BECN1 and BRCA1 in breast cancer, we studied their mRNA expression patterns in breast cancer patients from two large datasets: The Cancer Genome Atlas (TCGA (n = 1067 and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC (n = 1992. In both datasets, low expression of BECN1 was more common in HER2-enriched and basal-like (mostly triple-negative breast cancers compared to luminal A/B intrinsic tumor subtypes, and was also strongly associated with TP53 mutations and advanced tumor grade. In contrast, there was no significant association between low BRCA1 expression and HER2-enriched or basal-like subtypes, TP53 mutations or tumor grade. In addition, low expression of BECN1 (but not low BRCA1 was associated with poor prognosis, and BECN1 (but not BRCA1 expression was an independent predictor of survival. These findings suggest that decreased mRNA expression of the autophagy gene BECN1 may contribute to the pathogenesis and progression of HER2-enriched, basal-like, and TP53 mutant breast cancers.

  7. Enhanced Metastatic Recurrence Via Lymphatic Trafficking of a High-Metastatic Variant of Human Triple-Negative Breast Cancer After Surgical Resection in Orthotopic Nude Mouse Models.

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M

    2017-03-01

    We previously developed and characterized a highly invasive and metastatic triple-negative breast cancer (TNBC) variant by serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. Eventually, a highly invasive and metastatic variant of human TNBC was isolated after lymph node metastases was harvested and orthotopically re-implanted into the mammary gland of nude mice for two cycles. The variant thereby isolated is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present report, we observed that high-metastatic MDA-MB-231H-RFP cells produced significantly larger subcutaneous tumors compared with parental MDA-MB-231 cells in nude mice. Extensive lymphatic trafficking by high-metastatic MDA-MB-231 cells was also observed. High-metastatic MDA-MB-231 developed larger recurrent tumors 2 weeks after tumor resection compared with tumors that were not resected in orthotopic models. Surgical resection of the MDA-MB-231 high-metastatic variant primary tumor in orthotopic models also resulted in rapid and enhanced lymphatic trafficking of residual cancer cells and extensive lymph node and lung metastasis that did not occur in the non-surgical mice. These results suggest that surgical resection of high metastatic TNBC can greatly increase the malignancy of residual cancer. J. Cell. Biochem. 118: 559-569, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. A profile of NSAID-targeted arachidonic acid metabolisms in human embryonic stem cells (hESCs): implication of the negative effects of NSAIDs on heart tissue regeneration.

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    Chillar, Annirudha; So, Shui-Ping; Ruan, Cheng-Huai; Shelat, Harnath; Geng, Yong-Jian; Ruan, Ke-He

    2011-08-04

    An emerging technology using human embryonic stem cells (hESCs) to regenerate infarcted heart tissue has been underdeveloped. However, because non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, are taken during the infarction, it becomes critical to know whether the NSAIDs have negative impacts on heart tissue regeneration when using hESCs. Mass spectrometry (LC/MS/MS) and high performance liquid chromatography (HPLC) analyses were used to analyze the functional presence of the elaborate prostanoids' biosynthesis and signaling systems in hESCs. The detected endogenous arachidonic acid (AA) released in the hESC membranes reflects the activity of phospholipase which directly controls the biosyntheses of the prostanoids. The complete inhibition of the endogenous prostaglandin E(2) (PGE(2)) biosynthesis by the cyclooxygenase-2 (COX-2) inhibitor, NS398, confirmed that the major prostanoids synthesized in the hESCs are mediated by the COX-2 enzyme. We also found that PGE(2) and the prostacyclin (PGI(2)) metabolite, 6-keto-PGF(1α), are present in the undifferentiated hESCs. This indicated different cyclooxygenase (COX)-downstream synthases and metabolizing enzymes are involved in the AA products' signaling through the COX-1 and COX-2 pathways. The presence of many enzymes' and receptors' [(COX-1, COX-2, microsomal prostaglandin E synthase (mPGES), cytosolic prostaglandin E synthase (cPGES), prostaglandin I synthase (PGIS), the PGE(2) subtype receptors (EP(1), EP(2), and EP(4)) and the prostacyclin receptor (IP)] involvement in the prostanoid biosynthesis and activity was confirmed by western blot. The studies implied the negative effects of NSAIDs, such as aspirin and COX-2 inhibitors, which suppress prostanoid production during tissue regeneration for infarcted heart when using hESCs. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  9. Phosphorylation of clustered serine residues in the N-terminus of BPS domain negatively regulates formation of the complex between human Grb14 and insulin receptor.

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    Taira, Junichi; Kida, Yutaka; Inatomi, Kohei; Komatsu, Hideyuki; Higashimoto, Yuichiro; Sakamoto, Hiroshi

    2017-08-01

    Growth factor receptor-bound protein 14 (Grb14) is a negative regulator of insulin receptor (IR) and is involved in a negative feedback mechanism of insulin signaling. Grb14 associates with IR and inhibits its tyrosine kinase activity through the between pleckstrin homology and Src homology-2 (BPS) domain. We previously reported that the pharmacological inhibition and knockdown of glycogen synthase kinase-3 (GSK-3) facilitates the insulin-induced complex formation of human Grb14 (hGrb14) and IR, suggesting that GSK-3 suppresses hGrb14 recruitment to IR. This study further investigated a functional phosphorylation of the serine residues in hGrb14 BPS domain, identified as putative GSK-3 targets to verify an effect of GSK-3 on the hGrb14-IR complex formation. In vitro kinase assay using the motif-derived peptides showed that the serine residues located in N-terminal (Ser358, Ser362 and Ser366) and C-terminal (Ser419 and Ser423) regions of the BPS domain were phosphorylated by GSK-3. Co-immunoprecipitation and yeast two-hybrid (Y2H) experiments suggested that the negative charges genetically introduced on the Ser358, Ser362 and Ser366 suppressed the association of hGrb14 to IR. Surface plasmon resonance experiment gave Kd values of 8 nM for recombinant hGrb14 with respect to the interaction with IR β-subunit, and this affinity was lost after the replacements of the Ser358, Ser362 and Ser366 with glutamic acid residues. Y2H experiment with the BPS domain alone; however, did not show any difference owing to the same mutations. It is therefore evident that the N-terminus of the BPS domain plays an important role in the regulation of hGrb14-IR complex formation through phosphorylation, in addition to other domains. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  10. Prevalence and risk factors of anal human papillomavirus infection among HIV-negative men who have sex with men in Urumqi city of Xinjiang Uyghur Autonomous Region, China.

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    Tian Tian

    Full Text Available Infection with human papillomavirus (HPV is the most common sexually transmitted infection among men who have sex with men (MSM. Study on prevalence and risk factors of anal HPV infection among HIV-negative MSM in Northwestern China was rare.We performed a cross-sectional study of HPV prevalence using anal swab specimens among HIV-negative MSM in Urumqi city of Xinjiang Uyghur Autonomous Region, China between April 1st and October 30th in 2016. Prevalence of any anal HPV infection, high-risk and low-risk HPV infection was estimated. Risk factors associated with any anal HPV infection was analyzed using univariate and multivariate logistic regression models.Among 538 potential participants, 500(92.9% were recruited in this study. The genotyping results of anal HPV infection were available for all. Of them, 259 (51.8%, 190 (38.0% and 141(28.2% were positive for at least one of the targeted 37 HPV genotypes, high-risk HPV genotypes, and any low-risk HPV genotypes. The most prevalent anal HPV genotype was HPV 6(11.8%, followed by HPV 16(11.2%, HPV 11(10.8%, HPV 51(7.0% and HPV 18(5.4%.Among those infected with at least one of the targeted 37 anal HPV genotypes, 75(29.0%, 155(59.8% and 191(73.7% were infected with 2-valent, quadrivalent and 9-valent HPV vaccine-covered genotypes. Receptive anal intercourse in the past year was the only predictor of any anal HPV infection in multivariate logistic regression model.Prevalence of any anal HPV infection and high-risk HPV infection among HIV-negative MSM in Urumqi city of Xinjiang is high. The majority of genotypes detected in our study were covered by quadrivalent and 9-valent HPV vaccines. Regular anal exams and early HPV vaccination among MSM may be considered in future HPV prevention programs in Xinjiang, China.

  11. Identification of a putative binding site for negatively charged surfaces in the fibronectin type II domain of human factor XII--an immunochemical and homology modeling approach.

    Science.gov (United States)

    Citarella, F; te Velthuis, H; Helmer-Citterich, M; Hack, C E

    2000-12-01

    Monoclonal antibodies directed against functional sites of proteins provide useful tools for structure-function studies. Here we describe a mAb, KOK5, directed against the heavy chain region of human coagulation factor XII (FXII), which inhibits kaolin-induced clotting activity by preventing the binding of FXII to kaolin. Furthermore, mAb KOK5 enhances FXII susceptibility for cleavage by kallikrein and supports FXII autoactivation. Hence, mAb KOK5 likely is directed against the binding site of FXII for negatively charged surfaces. Screening of two phage-displayed random peptide libraries with mAb KOK5 selected phages that could be grouped on the basis of two amino acid consensus sequences: A) FXFQTPXW and B) HQ/LCTHR/KKC. Sequence A contains two motifs: one shares homology with FXII amino acid residues 30-33 (FPFQ), the second one with residues 57-60 (TPNF); both amino acid stretches belonging to the fibronectin type II domain of FXII. Sequence B also reveals homology with part of the fibronectin type II domain, i.e. the stretch 40-47 (HKCTHKGR). A three-dimensional model of FXII residues 28-65, obtained by homology modeling, indicated that the three amino acid stretches 30-33, 40-47 and 57-60 are close to each other and accessible for the solvent, i.e. in a form available for interaction with the monoclonal antibody, suggesting that mAb KOK5 recognizes a discontinuous epitope on the fibronectin type III domain of FXII. Peptides corresponding to FXII sequences 29-37 (FXII29-37) or 39-47 (FXII39-47), were synthesized and tested for the capability to inhibit FXII binding to negatively charged surfaces. Peptide FXII39-47 inhibited the binding of labeled FXII to kaolin and effectively prevented both dextran sulfate- and kaolin-induced activation of the contact system in plasma. Hence, we suggest that the fibronectin type II domain of FXII, in particular residues 39 to 47, contribute to the binding site of FXII for negatively charged surfaces.

  12. Incidence, Duration, Persistence, and Factors Associated With High-risk Anal Human Papillomavirus Persistence Among HIV-negative Men Who Have Sex With Men: A Multinational Study.

    Science.gov (United States)

    Nyitray, Alan G; Carvalho da Silva, Roberto J; Chang, Mihyun; Baggio, Maria Luiza; Ingles, Donna J; Abrahamsen, Martha; Papenfuss, Mary; Lin, Hui-Yi; Salmerón, Jorge; Quiterio, Manuel; Lazcano-Ponce, Eduardo; Villa, Luisa L; Giuliano, Anna R

    2016-06-01

    Given high rates of anal disease, we investigated the natural history of high-risk anal human papillomavirus (HPV) among a multinational group of men who have sex with men (MSM) aged 18-64 years. Anal specimens from human immunodeficiency virus-negative men from Brazil, Mexico, and the United States were genotyped. Over 2 years, 406 MSM provided evaluable specimens every 6 months for ≥2 visits. These men were stratified into men who have sex only with men (MSOM, n = 70) and men who have sex with women and men (MSWM, n = 336). Persistence was defined as ≥12 months' type-specific duration and could begin with either a prevalent or incident infection. Prevalence ratios and 95% confidence intervals were calculated by Poisson regression. Median follow-up time was 2.1 years. Retention was 82%. Annual cumulative incidence of 9-valent vaccine types was 19% and 8% among MSOM and MSWM, respectively (log-rank P = .02). Duration of anal HPV did not differ for MSOM and MSWM and was a median of 6.9 months for HPV-16 after combining men from the 2 groups. Among men with prevalent high-risk infection (n = 106), a total of 36.8%, retained the infection for at least 24 months. For those with prevalent HPV-16 (n = 27), 29.6% were persistent for at least 24 months. Persistence of high-risk HPV was associated with number of male anal sex partners and inversely associated with number of female sex partners. MSM with prevalent high-risk HPV infection should be considered at increased risk for nontransient infection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  13. Incidence, Duration, Persistence, and Factors Associated With High-risk Anal Human Papillomavirus Persistence Among HIV-negative Men Who Have Sex With Men: A Multinational Study

    Science.gov (United States)

    Nyitray, Alan G.; Carvalho da Silva, Roberto J.; Chang, Mihyun; Baggio, Maria Luiza; Ingles, Donna J.; Abrahamsen, Martha; Papenfuss, Mary; Lin, Hui-Yi; Salmerón, Jorge; Quiterio, Manuel; Lazcano-Ponce, Eduardo; Villa, Luisa L.; Giuliano, Anna R.

    2016-01-01

    Background. Given high rates of anal disease, we investigated the natural history of high-risk anal human papillomavirus (HPV) among a multinational group of men who have sex with men (MSM) aged 18–64 years. Methods. Anal specimens from human immunodeficiency virus–negative men from Brazil, Mexico, and the United States were genotyped. Over 2 years, 406 MSM provided evaluable specimens every 6 months for ≥2 visits. These men were stratified into men who have sex only with men (MSOM, n = 70) and men who have sex with women and men (MSWM, n = 336). Persistence was defined as ≥12 months’ type-specific duration and could begin with either a prevalent or incident infection. Prevalence ratios and 95% confidence intervals were calculated by Poisson regression. Results. Median follow-up time was 2.1 years. Retention was 82%. Annual cumulative incidence of 9-valent vaccine types was 19% and 8% among MSOM and MSWM, respectively (log-rank P = .02). Duration of anal HPV did not differ for MSOM and MSWM and was a median of 6.9 months for HPV-16 after combining men from the 2 groups. Among men with prevalent high-risk infection (n = 106), a total of 36.8%, retained the infection for at least 24 months. For those with prevalent HPV-16 (n = 27), 29.6% were persistent for at least 24 months. Persistence of high-risk HPV was associated with number of male anal sex partners and inversely associated with number of female sex partners. Conclusions. MSM with prevalent high-risk HPV infection should be considered at increased risk for nontransient infection. PMID:26962079

  14. Negative regulation of mitosis in fission yeast by the shk1 interacting protein skb1 and its human homolog, Skb1Hs.

    Science.gov (United States)

    Gilbreth, M; Yang, P; Bartholomeusz, G; Pimental, R A; Kansra, S; Gadiraju, R; Marcus, S

    1998-12-08

    We previously provided evidence that the protein encoded by the highly conserved skb1 gene is a putative regulator of Shk1, a p21(Cdc42/Rac)-activated kinase (PAK) homolog in the fission yeast Schizosaccharomyces pombe. skb1 null mutants are viable and competent for mating but less elongate than wild-type S. pombe cells, whereas cells that overexpress skb1 are hyperelongated. These phenotypes suggest a possible role for Skb1 as a mitotic inhibitor. Here we show genetic interactions of both skb1 and shk1 with genes encoding key mitotic regulators in S. pombe. Our results indicate that Skb1 negatively regulates mitosis by a mechanism that is independent of the Cdc2-activating phosphatase Cdc25 but that is at least partially dependent on Shk1 and the Cdc2 inhibitory kinase Wee1. We provide biochemical evidence for association of Skb1 and Shk1 with Cdc2 in S. pombe, suggesting that Skb1 and Shk1 inhibit mitosis through interaction with the Cdc2 complex, rather than by an indirect mechanism. These results provide evidence of a previously undescribed role for PAK-related protein kinases as mitotic inhibitors. We also describe the cloning of a human homolog of skb1, SKB1Hs, and show that it can functionally replace skb1 in S. pombe. Thus, the molecular functions of Skb1-related proteins have likely been substantially conserved through evolution.

  15. Evaluation of techniques for the diagnosis of Strongyloides stercoralis in human immunodeficiency virus (HIV positive and HIV negative individuals in the city of Itajaí, Brazil

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    Jucelene Marchi Blatt

    Full Text Available Human immunodeficiency virus (HIV and intestinal parasites are common in Brazil. Previous studies have shown that infection with Strongyloides stercoralis is frequently associated with HIV infection. Strongyloidiasis is difficult to diagnosis and stool examination with conventional techniques fails to detect the helminth larvae. We made a prospective study, to test the efficacy of the agar plate technique to detect S. stercoralis in 211 HIV-positive patients and 213 HIV-negative patients in the city of Itajaí, Brazil, between September 2001 and June 2002. The feces samples of these patients were processed and analyzed according to the following methods: Lutz, formalin ethyl acetate, Baermann, Harada-Mori and agar plate culture. HIV-positive patients were more frequently infected by S. stercoralis (odds ratio= 5,.687. Among the methods used on fecal specimens, the larvae of S. stercoralis were most efficiently detected by the agar plate (69.7% method, followed by the Baermann and the formalin ethyl acetate methods (48.5% (P=0.01, Lutz (42.4% (P=0.01, and Harada-Mori culture (24% (P=0.001. Therefore agar plate culture is the most efficient method for the detection of S. stercoralis larvae and this technique should be the test of choice, especially in immunocompromised patients.

  16. A model to estimate the probability of human immunodeficiency virus and hepatitis C infection despite negative nucleic acid testing among increased-risk organ donors.

    Science.gov (United States)

    Annambhotla, Pallavi D; Gurbaxani, Brian M; Kuehnert, Matthew J; Basavaraju, Sridhar V

    2017-04-01

    In 2013, guidelines were released for reducing the risk of viral bloodborne pathogen transmission through organ transplantation. Eleven criteria were described that result in a donor being designated at increased infectious risk. Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) transmission risk from an increased-risk donor (IRD), despite negative nucleic acid testing (NAT), likely varies based on behavior type and timing. We developed a Monte Carlo risk model to quantify probability of HIV among IRDs. The model included NAT performance, viral load dynamics, and per-act risk of acquiring HIV by each behavior. The model also quantifies the probability of HCV among IRDs by non-medical intravenous drug use (IVDU). Highest risk is among donors with history of unprotected, receptive anal male-to-male intercourse with partner of unknown HIV status (MSM), followed by sex with an HIV-infected partner, IVDU, and sex with a commercial sex worker. With NAT screening, the estimated risk of undetected HIV remains small even at 1 day following a risk behavior. The estimated risk for HCV transmission through IVDU is likewise small and decreases quicker with time owing to the faster viral growth dynamics of HCV compared with HIV. These findings may allow for improved organ allocation, utilization, and recipient informed consent. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Real-World Treatment Patterns for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer in Europe and the United States.

    Science.gov (United States)

    Caldeira, Rita; Scazafave, Mark

    2016-01-01

    Clinical guidelines generally recommend endocrine therapy over chemotherapy for hormone receptor-positive advanced breast cancer (unless life-threatening metastases are present). This study aimed to assess the real-world treatment patterns of patients with hormone receptor-positive advanced breast cancer in Europe and the United States. Treatment patterns in Europe (France, Germany, Italy, Spain, and the UK) and the United States from January 2012 to December 2014 were investigated using a patient record database (Global Oncology Monitor©). Sample data were projected to the wider clinical population to provide running annual estimates every 3 months. Sample sizes ranged from 1272 to 1640 patients in Europe and from 2225 to 2760 patients in the United States. Across all lines of therapy, 37-43% (Europe) and 45-50% (United States) of patients received chemotherapy. More patients received endocrine therapy than chemotherapy as first-line treatment for advanced breast cancer (Europe: 51-54% vs. 33-35%; United States: 53-60% vs. 34-42%). In contrast, endocrine therapy-only regimens were given less commonly than chemotherapy-only regimens in the third-line setting in both Europe and the United States. Chemotherapy is used extensively in routine clinical practice for hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The results also suggest that the treatment patternsin Europe and the United States are qualitatively different. Funding : Ipsos Healthcare and AstraZeneca.

  18. The DNA methylation signature of human TCRαβ+CD4−CD8− double negative T cells reveals CG demethylation and a unique epigenetic architecture permissive to a broad stimulatory immune response

    Science.gov (United States)

    Renauer, Paul A.; Coit, Patrick; Sawalha, Amr H.

    2014-01-01

    T cell receptor (TCR) αβ+CD4−CD8− double negative T cells represent a rare T cell subset implicated in the pathogenesis of several autoimmune diseases. We investigated the DNA methylation signature of double negative T cells to gain insight into the epigenetic architecture of peripheral blood primary human double negative T cells compared to autologous CD4+ and CD8+ T cells. We identified 2984 CG sites across the genome with unique loss of DNA methylation in double negative T cells, and showed significant reduction in mRNA expression of DNA methyltransferases DNMT1, DNMT3A, and DNMT3B. DNA methylation was increased in CD8A/CD8B and CD4 consistent with epigenetic repression of both the CD8 and CD4 genetic loci in double negative T cells. We show a consistent increase in non-CG methylation in double negative T cells, a finding suggestive of pluripotency. Network analyses indicate a strong relationship between double negative T cells and functions related to cell –cell interaction, cell adhesion, and cell activation pathways. Our data also suggest a robust pro-inflammatory epigenetic signature in double negative T cells, consistent with a transcriptional permissiveness in key inflammatory cytokines including IFNγ, IL-17F, IL-12B, IL-5, IL-18, TNFSF11 (RANKL), and TNFSF13B (BLYS or BAFF). These findings highlight an epigenetic basis for a role of double negative T cells in autoimmunity. PMID:25451162

  19. The DNA methylation signature of human TCRαβ+CD4-CD8- double negative T cells reveals CG demethylation and a unique epigenetic architecture permissive to a broad stimulatory immune response.

    Science.gov (United States)

    Renauer, Paul A; Coit, Patrick; Sawalha, Amr H

    2015-01-01

    T cell receptor (TCR) αβ+CD4-CD8- double negative T cells represent a rare T cell subset implicated in the pathogenesis of several autoimmune diseases. We investigated the DNA methylation signature of double negative T cells to gain insight into the epigenetic architecture of peripheral blood primary human double negative T cells compared to autologous CD4+ and CD8+ T cells. We identified 2984 CG sites across the genome with unique loss of DNA methylation in double negative T cells, and showed significant reduction in mRNA expression of DNA methyltransferases DNMT1, DNMT3A, and DNMT3B. DNA methylation was increased in CD8A/CD8B and CD4 consistent with epigenetic repression of both the CD8 and CD4 genetic loci in double negative T cells. We show a consistent increase in non-CG methylation in double negative T cells, a finding suggestive of pluripotency. Network analyses indicate a strong relationship between double negative T cells and functions related to cell-cell interaction, cell adhesion, and cell activation pathways. Our data also suggest a robust pro-inflammatory epigenetic signature in double negative T cells, consistent with a transcriptional permissiveness in key inflammatory cytokines including IFNγ, IL-17F, IL-12B, IL-5, IL-18, TNFSF11 (RANKL), and TNFSF13B (BLYS or BAFF). These findings highlight an epigenetic basis for a role of double negative T cells in autoimmunity. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. The natural compound Jatrophone interferes with Wnt/β-catenin signaling and inhibits proliferation and EMT in human triple-negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Iram Fatima

    Full Text Available Metastatic breast cancer is the leading cause of worldwide cancer-related deaths among women. Triple negative breast cancers (TNBC are highly metastatic and are devoid of estrogen receptor (ER, progesterone receptor (PR and human epidermal growth factor receptor 2 (HER2 amplification. TNBCs are unresponsive to Herceptin and/or anti-estrogen therapies and too often become highly chemoresistant when exposed to standard chemotherapy. TNBCs frequently metastasize to the lung and brain. We have previously shown that TNBCs are active for oncogenic Wnt10b/β-catenin signaling and that WNT10B ligand and its downstream target HMGA2 are predictive of poorer outcomes and are strongly associated with chemoresistant TNBC metastatic disease. In search of new chemicals to target the oncogenic WNT10B/β-CATENIN/HMGA2 signaling axis, the anti-proliferative activity of the diterpene Jatrophone (JA, derived from the plant Jatropha isabelli, was tested on TNBC cells. JA interfered with the WNT TOPFLASH reporter at the level between receptor complex and β-catenin activation. JA efficacy was determined in various subtypes of TNBC conventional cell lines or in TNBC cell lines derived from TNBC PDX tumors. The differential IC50 (DCI50 responsiveness was compared among the TNBC models based on etiological-subtype and their cellular chemoresistance status. Elevated WNT10B expression also coincided with increased resistance to JA exposure in several metastatic cell lines. JA interfered with cell cycle progression, and induced loss of expression of the canonical Wnt-direct targets genes AXIN2, HMGA2, MYC, PCNA and CCND1. Mechanistically, JA reduced steady-state, non-phosphorylated (activated β-catenin protein levels, but not total β-catenin levels. JA also caused the loss of expression of key EMT markers and significantly impaired wound healing in scratch assays, suggesting a direct role for JA inhibiting migration of TNBC cells. These results indicate that Jatrophone

  1. [Arsenic trioxide restores ERα expression in ERα-negative human breast cancer cells and its treatment efficacy in combination with tamoxifen in xenografts in nude mice].

    Science.gov (United States)

    Zhang, Wei-jie; Xu, Deng-fei; Fan, Qing-xia; Wu, Xin-ai; Wang, Feng; Wang, Rui; Wang, Liu-xing

    2012-09-01

    To study the demethylation effect of arsenic trioxide (As2O3) on ERα-negative human breast cancer MDA-MB-435s cells and its possible mechanisms, and to observe its treatment efficacy in combination with tamoxifen (TAM) after ERα re-expression. MTT assay was used to examine the inhibitory effect of As2O3 treatment alone or in combination with TAM on cell proliferation. A nude mouse xenograft model was used to further examine the treatment efficacy in vivo. MSP was used to detect the methylation status of ERα gene after treated with As2O3 in MDA-MB-435s cells and the transplanted tumor tissues. RT-PCR was used to detect the mRNA expression of DNMT1 and Erα. Western bolt was used to detect the DNMT1 and ERα protein expression. The diameter of xenograft tumors was measured weekly, and the tumor growth curve was drawn. The level of proliferation of the MDA-MB-435s cells was significantly suppressed after treatment with different concentration of As2O3 alone or As2O3 combined with TAM, and the 4 µmol/L As2O3 + TAM treatment for 72 h showed the highest inhibition rate (62.6%). 1, 2, 4 µmol/L As2O3 had demethylation effect on MDA-MB-435s cells, and the DNMT1 mRNA and protein expression was inhibited and accompanied by ERα mRNA and protein re-expression. The unmethylation specific bands of ERα gene were enhanced after treated by As2O3 alone or As2O3 combined with TAM in the xenograft tumors. The expression of DNMT1 mRNA and protein was inhibited, and accompanied by ERα mRNA and protein re-expression. An significant decrease of volume and weight of the xenograft tumors in the As2O3 treated alone or combined with TAM groups was observed compared with those of the normal saline group or TAM alone group (P breast cancer MDA-MB-435s cells after treated with As2O3 by inhibiting the DNMT1 activity. MDA-MB-435s cells are re-sensitized to endocrine therapy after ERα re-expression. As2O3 combined with TAM may provide a new therapeutic approach for patients with ERα-negative

  2. ERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancer

    Science.gov (United States)

    Abreu, Rui M. V.; Bastos, Estela; Amorim, Irina; Gut, Ivo G.; Gärtner, Fátima; Chaves, Raquel

    2013-01-01

    Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2 (27%–59.6%) has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10–15) was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination), mRNA (expression levels assessment) and protein levels (in extra- and intra protein domains) in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2 negative HBC

  3. Baicalin downregulates Porphyromonas gingivalis lipopolysaccharide-upregulated IL-6 and IL-8 expression in human oral keratinocytes by negative regulation of TLR signaling.

    Directory of Open Access Journals (Sweden)

    Wei Luo

    Full Text Available Periodontal (gum disease is one of the main global oral health burdens and severe periodontal disease (periodontitis is a leading cause of tooth loss in adults globally. It also increases the risk of cardiovascular disease and diabetes mellitus. Porphyromonas gingivalis lipopolysaccharide (LPS is a key virulent attribute that significantly contributes to periodontal pathogenesis. Baicalin is a flavonoid from Scutellaria radix, an herb commonly used in traditional Chinese medicine for treating inflammatory diseases. The present study examined the modulatory effect of baicalin on P. gingivalis LPS-induced expression of IL-6 and IL-8 in human oral keratinocytes (HOKs. Cells were pre-treated with baicalin (0-80 µM for 24 h, and subsequently treated with P. gingivalis LPS at 10 µg/ml with or without baicalin for 3 h. IL-6 and IL-8 transcripts and proteins were detected by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The expression of nuclear factor-κB (NF-κB, p38 mitogen-activated protein kinase (MAPK and c-Jun N-terminal kinase (JNK proteins was analyzed by western blot. A panel of genes related to toll-like receptor (TLR signaling was examined by PCR array. We found that baicalin significantly downregulated P. gingivalis LPS-stimulated expression of IL-6 and IL-8, and inhibited P. gingivalis LPS-activated NF-κB, p38 MAPK and JNK. Furthermore, baicalin markedly downregulated P. gingivalis LPS-induced expression of genes associated with TLR signaling. In conclusion, the present study shows that baicalin may significantly downregulate P. gingivalis LPS-upregulated expression of IL-6 and IL-8 in HOKs via negative regulation of TLR signaling.

  4. Quorum Sensing Down-Regulation Counteracts the Negative Impact of Pseudomonas aeruginosa on CFTR Channel Expression, Function and Rescue in Human Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Émilie Maillé

    2017-11-01

    Full Text Available The function of cystic fibrosis transmembrane conductance regulator (CFTR channels is crucial in human airways. However unfortunately, chronic Pseudomonas aeruginosa infection has been shown to impair CFTR proteins in non-CF airway epithelial cells (AEC and to alter the efficiency of new treatments with CFTR modulators designed to correct the basic CFTR default in AEC from cystic fibrosis (CF patients carrying the F508del mutation. Our aim was first to compare the effect of laboratory strains, clinical isolates, engineered and natural mutants to determine the role of the LasR quorum sensing system in CFTR impairment, and second, to test the efficiency of a quorum sensing inhibitor to counteract the deleterious impact of P. aeruginosa both on wt-CFTR and on the rescue of F508del-CFTR by correctors. We first report that exoproducts from either the laboratory PAO1 strain or a clinical ≪Early≫ isolate (from an early stage of infection altered CFTR expression, localization and function in AEC expressing wt-CFTR. Genetic inactivation of the quorum-sensing LasR in PAO1 (PAO1ΔlasR or in a natural clinical mutant (≪Late≫ CF-adapted clinical isolate abolished wt-CFTR impairment. PAO1 exoproducts also dampened F508del-CFTR rescue by VRT-325 or Vx-809 correctors in CF cells, whereas PAO1ΔlasR had no impact. Importantly, treatment of P. aeruginosa cultures with a quorum sensing inhibitor (HDMF prevented the negative effect of P. aeruginosa exoproducts on wt-CFTR and preserved CFTR rescue by correctors in CF AEC. These findings indicate that LasR-interfering strategies could be of benefits to counteract the deleterious effect of P. aeruginosa in infected patients.

  5. Quorum Sensing Down-Regulation Counteracts the Negative Impact of Pseudomonas aeruginosa on CFTR Channel Expression, Function and Rescue in Human Airway Epithelial Cells.

    Science.gov (United States)

    Maillé, Émilie; Ruffin, Manon; Adam, Damien; Messaoud, Hatem; Lafayette, Shantelle L; McKay, Geoffrey; Nguyen, Dao; Brochiero, Emmanuelle

    2017-01-01

    The function of cystic fibrosis transmembrane conductance regulator (CFTR) channels is crucial in human airways. However unfortunately, chronic Pseudomonas aeruginosa infection has been shown to impair CFTR proteins in non-CF airway epithelial cells (AEC) and to alter the efficiency of new treatments with CFTR modulators designed to correct the basic CFTR default in AEC from cystic fibrosis (CF) patients carrying the F508del mutation. Our aim was first to compare the effect of laboratory strains, clinical isolates, engineered and natural mutants to determine the role of the LasR quorum sensing system in CFTR impairment, and second, to test the efficiency of a quorum sensing inhibitor to counteract the deleterious impact of P. aeruginosa both on wt-CFTR and on the rescue of F508del-CFTR by correctors. We first report that exoproducts from either the laboratory PAO1 strain or a clinical ≪Early≫ isolate (from an early stage of infection) altered CFTR expression, localization and function in AEC expressing wt-CFTR. Genetic inactivation of the quorum-sensing LasR in PAO1 (PAO1ΔlasR) or in a natural clinical mutant (≪Late≫ CF-adapted clinical isolate) abolished wt-CFTR impairment. PAO1 exoproducts also dampened F508del-CFTR rescue by VRT-325 or Vx-809 correctors in CF cells, whereas PAO1ΔlasR had no impact. Importantly, treatment of P. aeruginosa cultures with a quorum sensing inhibitor (HDMF) prevented the negative effect of P. aeruginosa exoproducts on wt-CFTR and preserved CFTR rescue by correctors in CF AEC. These findings indicate that LasR-interfering strategies could be of benefits to counteract the deleterious effect of P. aeruginosa in infected patients.

  6. Disease management patterns for postmenopausal women in Europe with hormone-receptor-positive, human epidermal growth factor receptor-2 negative advanced breast cancer.

    Science.gov (United States)

    André, Fabrice; Neven, Patrick; Marinsek, Nina; Zhang, Jie; Baladi, Jean-Francois; Degun, Ravi; Benelli, Giancarlo; Saletan, Stephen; Jerusalem, Guy

    2014-06-01

    International guidelines for hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2 negative (HER2(-)) advanced breast cancer (BC) recommend sequential lines of hormonal therapy (HT), and only recommend chemotherapy for patients with extensive visceral involvement or rapidly progressive disease. This study evaluated actual physician-reported treatments for advanced BC in Europe. We conducted a retrospective chart review of 355 postmenopausal women with HR(+), HER2(-) advanced BC who progressed on ≥1 line of HT (adjuvant or advanced) and completed ≥1 line of chemotherapy (advanced). Treatment choice was evaluated for each line of therapy. Of 355 patients, 111 (31%) received first-line chemotherapy, whereas 218 (61%) and 26 (7%) switched from HT to chemotherapy in second and third line, respectively. More patients receiving first-line HT had bone metastases (73% vs 27% chemotherapy). Patients treated with first-line chemotherapy had more brain (12% vs 3% HT) or extensive liver (13% vs 6% HT) metastases. Subgroup analysis of 188 patients who received first-line HT and had de novo advanced BC or relapsed/recurrent disease more than 1 year after adjuvant therapy found that the majority (89%; n = 167) of these patients switched to chemotherapy in second line. However, among these 167 patients, 27% had no significant changes in metastases between first and second line. Among the 73% of patients who had significant changes in metastases, 20% had no brain metastases or extensive visceral disease. Our study suggests that the guideline-recommended use of multiple HT lines is open to interpretation and that optimal treatment for European postmenopausal women with HR(+), HER2(-) advanced BC who responded to HT may not be achieved.

  7. Inferring Aggregated Functional Traits from Metagenomic Data Using Constrained Non-negative Matrix Factorization: Application to Fiber Degradation in the Human Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Sébastien Raguideau

    2016-12-01

    Full Text Available Whole Genome Shotgun (WGS metagenomics is increasingly used to study the structure and functions of complex microbial ecosystems, both from the taxonomic and functional point of view. Gene inventories of otherwise uncultured microbial communities make the direct functional profiling of microbial communities possible. The concept of community aggregated trait has been adapted from environmental and plant functional ecology to the framework of microbial ecology. Community aggregated traits are quantified from WGS data by computing the abundance of relevant marker genes. They can be used to study key processes at the ecosystem level and correlate environmental factors and ecosystem functions. In this paper we propose a novel model based approach to infer combinations of aggregated traits characterizing specific ecosystemic metabolic processes. We formulate a model of these Combined Aggregated Functional Traits (CAFTs accounting for a hierarchical structure of genes, which are associated on microbial genomes, further linked at the ecosystem level by complex co-occurrences or interactions. The model is completed with constraints specifically designed to exploit available genomic information, in order to favor biologically relevant CAFTs. The CAFTs structure, as well as their intensity in the ecosystem, is obtained by solving a constrained Non-negative Matrix Factorization (NMF problem. We developed a multicriteria selection procedure for the number of CAFTs. We illustrated our method on the modelling of ecosystemic functional traits of fiber degradation by the human gut microbiota. We used 1408 samples of gene abundances from several high-throughput sequencing projects and found that four CAFTs only were needed to represent the fiber degradation potential. This data reduction highlighted biologically consistent functional patterns while providing a high quality preservation of the original data. Our method is generic and can be applied to other

  8. Evaluation of HIV and Highly Active Antiretroviral Therapy on the Natural History of Human Papillomavirus Infection and Cervical Cytopathologic Findings in HIV-Positive and High-Risk HIV-Negative Women

    NARCIS (Netherlands)

    Blitz, Sandra; Baxter, Joanna; Raboud, Janet; Walmsley, Sharon; Rachlis, Anita; Smaill, Fiona; Ferenczy, Alex; Coutlée, François; Hankins, Catherine; Money, Deborah

    2013-01-01

    Background. The Canadian Women's HIV Study (CWHS) enrolled human immunodeficiency virus (HIV)-positive and high-risk HIV-negative women in a longitudinal cohort. This analysis considered the effects of HIV and highly active antiretroviral therapy (HAART) on HPV persistence and cervical squamous

  9. A mouse model for triple-negative breast cancer tumor-initiating cells (TNBC-TICs) exhibits similar aggressive phenotype to the human disease.

    Science.gov (United States)

    Kaur, Punit; Nagaraja, Ganachari M; Zheng, Hongying; Gizachew, Dawit; Galukande, Moses; Krishnan, Sunil; Asea, Alexzander

    2012-03-27

    Triple-negative breast cancer (TNBC) exhibit characteristics quite distinct from other kinds of breast cancer, presenting as an aggressive disease--recurring and metastasizing more often than other kinds of breast cancer, without tumor-specific treatment options and accounts for 15% of all types of breast cancer with higher percentages in premenopausal African-American and Hispanic women. The reason for this aggressive phenotype is currently the focus of intensive research. However, progress is hampered by the lack of suitable TNBC cell model systems. To understand the mechanistic basis for the aggressiveness of TNBC, we produced a stable TNBC cell line by sorting for 4T1 cells that do not express the estrogen receptor (ER), progesterone receptor (PgR) or the gene for human epidermal growth factor receptor 2 (HER2). As a control, we produced a stable triple-positive breast cancer (TPBC) cell line by transfecting 4T1 cells with rat HER2, ER and PgR genes and sorted for cells with high expression of ER and PgR by flow cytometry and high expression of the HER2 gene by Western blot analysis. We isolated tumor-initiating cells (TICs) by sorting for CD24+/CD44high/ALDH1+ cells from TNBC (TNBC-TICs) and TPBC (TPBC-TICs) stable cell lines. Limiting dilution transplantation experiments revealed that CD24+/CD44high/ALDH1+ cells derived from TNBC (TNBC-TICs) and TPBC (TPBC-TICs) were significantly more effective at repopulating the mammary glands of naïve female BALB/c mice than CD24-/CD44-/ALDH1- cells. Implantation of the TNBC-TICs resulted in significantly larger tumors, which metastasized to the lungs to a significantly greater extent than TNBC, TPBC-TICs, TPBC or parental 4T1 cells. We further demonstrated that the increased aggressiveness of TNBC-TICs correlates with the presence of high levels of mouse twenty-five kDa heat shock protein (Hsp25/mouse HspB1) and seventy-two kDa heat shock protein (Hsp72/HspA1A). Taken together, we have developed a TNBC-TICs model system

  10. Budget impact analysis of everolimus for the treatment of hormone receptor positive, human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer in the United States.

    Science.gov (United States)

    Xie, Jipan; Diener, Melissa; De, Gourab; Yang, Hongbo; Wu, Eric Q; Namjoshi, Madhav

    2013-01-01

    To estimate the budget impact of everolimus as the first and second treatment option after letrozole or anastrozole (L/A) failure for post-menopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (ABC). Pharmacy and medical budget impacts (2011 USD) were estimated over the first year of everolimus use in HR+, HER2- ABC from a US payer perspective. Epidemiology data were used to estimate target population size. Pre-everolimus entry treatment options included exemestane, fulvestrant, and tamoxifen. Pre- and post-everolimus entry market shares were estimated based on market research and assumptions. Drug costs were based on wholesale acquisition cost. Patients were assumed to be on treatment until progression or death. Annual medical costs were calculated as the average of pre- and post-progression medical costs weighted by the time in each period, adjusted for survival. One-way and two-way sensitivity analyses were conducted to assess the model robustness. In a hypothetical 1,000,000 member plan, 72 and 159 patients were expected to be candidates for everolimus treatment as first and second treatment option, respectively, after L/A failure. The total budget impact for the first year post-everolimus entry was $0.044 per member per month [PMPM] (pharmacy budget: $0.058 PMPM; medical budget: -$0.014 PMPM), assuming 10% of the target population would receive everolimus. The total budget impacts for the first and second treatment options after L/A failure were $0.014 PMPM (pharmacy budget: $0.018; medical budget: -$0.004) and $0.030 PMPM (pharmacy budget: $0.040; medical budget: -$0.010), respectively. Results remained robust in sensitivity analyses. Assumptions about some model input parameters were necessary and may impact results. Increased pharmacy costs for HR+, HER2- ABC following everolimus entry are expected to be partially offset by reduced medical service costs. Pharmacy and total

  11. A mouse model for triple-negative breast cancer tumor-initiating cells (TNBC-TICs exhibits similar aggressive phenotype to the human disease

    Directory of Open Access Journals (Sweden)

    Kau Punit

    2012-03-01

    Full Text Available Abstract Background Triple-negative breast cancer (TNBC exhibit characteristics quite distinct from other kinds of breast cancer, presenting as an aggressive disease--recurring and metastasizing more often than other kinds of breast cancer, without tumor-specific treatment options and accounts for 15% of all types of breast cancer with higher percentages in premenopausal African-American and Hispanic women. The reason for this aggressive phenotype is currently the focus of intensive research. However, progress is hampered by the lack of suitable TNBC cell model systems. Methods To understand the mechanistic basis for the aggressiveness of TNBC, we produced a stable TNBC cell line by sorting for 4T1 cells that do not express the estrogen receptor (ER, progesterone receptor (PgR or the gene for human epidermal growth factor receptor 2 (HER2. As a control, we produced a stable triple-positive breast cancer (TPBC cell line by transfecting 4T1 cells with rat HER2, ER and PgR genes and sorted for cells with high expression of ER and PgR by flow cytometry and high expression of the HER2 gene by Western blot analysis. Results We isolated tumor-initiating cells (TICs by sorting for CD24+/CD44high/ALDH1+ cells from TNBC (TNBC-TICs and TPBC (TPBC-TICs stable cell lines. Limiting dilution transplantation experiments revealed that CD24+/CD44high/ALDH1+ cells derived from TNBC (TNBC-TICs and TPBC (TPBC-TICs were significantly more effective at repopulating the mammary glands of naïve female BALB/c mice than CD24-/CD44-/ALDH1- cells. Implantation of the TNBC-TICs resulted in significantly larger tumors, which metastasized to the lungs to a significantly greater extent than TNBC, TPBC-TICs, TPBC or parental 4T1 cells. We further demonstrated that the increased aggressiveness of TNBC-TICs correlates with the presence of high levels of mouse twenty-five kDa heat shock protein (Hsp25/mouse HspB1 and seventy-two kDa heat shock protein (Hsp72/HspA1A. Conclusions

  12. Prevalence of and Risk Factors for Oral Human Papillomavirus Infection among HIV-Positive and HIV-Negative People Who Inject Drugs.

    Science.gov (United States)

    Robbins, Hilary A; Fennell, Christina E; Gillison, Maura; Xiao, Weihong; Guo, Yingshi; Wentz, Alicia; Kirk, Gregory D; Mehta, Shruti H; D'Souza, Gypsyamber

    2015-01-01

    Human papillomavirus (HPV) causes most oropharyngeal cancers in the United States. Oral HPV prevalence is associated with immunosuppression, and drug use can be immunosuppressive, but the epidemiology of oral HPV among people who use drugs is not well described. We enrolled men and women with a current or prior history of injection drug use in this cross-sectional sub-study within the AIDS Linked to the Intravenous Experience (ALIVE) cohort. We tested oral rinse samples for 37 types of HPV DNA and collected self-reported risk factor information. We compared oral HPV prevalence across categories using chi-squared statistics and multivariable logistic regression. Among 199 subjects, 32% were HIV-positive (median CD4 count 384 cells/μL), 90% were Black, 56% had less than a high school education, 17% had recently used injection drugs, and the median age was 54 years. Most had performed oral sex (82%) but had fewer than 5 lifetime partners (58%). The prevalence of any oral HPV was 29%, and of any oncogenic oral HPV was 13%. Oral HPV prevalence was high among both heterosexual men (30%) and women (20%). After adjustment, odds of oral HPV were increased among HIV-positive individuals with a low CD4 count (vs. HIV-negative individuals), but not among HIV-positive individuals with a higher CD4 cell count. Odds were also elevated for those who had recently performed oral sex on a woman (aOR = 2.2, 95%CI = 1.01-4.6) and, even after this adjustment, among bisexual/lesbian females (aOR = 5.6, 95%CI = 1.4-23, vs. heterosexual females). Oral HPV prevalence was not associated with vaginal sex, performing oral sex on a man, or recent drug use. Recent drug use was not associated with oral HPV prevalence in our study. However, despite modest numbers of sexual partners, the prevalence of oral HPV among this largely Black population with lower socioeconomic status was high.

  13. Prevalence of and Risk Factors for Oral Human Papillomavirus Infection among HIV-Positive and HIV-Negative People Who Inject Drugs.

    Directory of Open Access Journals (Sweden)

    Hilary A Robbins

    Full Text Available Human papillomavirus (HPV causes most oropharyngeal cancers in the United States. Oral HPV prevalence is associated with immunosuppression, and drug use can be immunosuppressive, but the epidemiology of oral HPV among people who use drugs is not well described.We enrolled men and women with a current or prior history of injection drug use in this cross-sectional sub-study within the AIDS Linked to the Intravenous Experience (ALIVE cohort. We tested oral rinse samples for 37 types of HPV DNA and collected self-reported risk factor information. We compared oral HPV prevalence across categories using chi-squared statistics and multivariable logistic regression.Among 199 subjects, 32% were HIV-positive (median CD4 count 384 cells/μL, 90% were Black, 56% had less than a high school education, 17% had recently used injection drugs, and the median age was 54 years. Most had performed oral sex (82% but had fewer than 5 lifetime partners (58%. The prevalence of any oral HPV was 29%, and of any oncogenic oral HPV was 13%. Oral HPV prevalence was high among both heterosexual men (30% and women (20%. After adjustment, odds of oral HPV were increased among HIV-positive individuals with a low CD4 count (<350 cells/μl, aOR = 2.7, 95%CI = 1.2-6.4, vs. HIV-negative individuals, but not among HIV-positive individuals with a higher CD4 cell count. Odds were also elevated for those who had recently performed oral sex on a woman (aOR = 2.2, 95%CI = 1.01-4.6 and, even after this adjustment, among bisexual/lesbian females (aOR = 5.6, 95%CI = 1.4-23, vs. heterosexual females. Oral HPV prevalence was not associated with vaginal sex, performing oral sex on a man, or recent drug use.Recent drug use was not associated with oral HPV prevalence in our study. However, despite modest numbers of sexual partners, the prevalence of oral HPV among this largely Black population with lower socioeconomic status was high.

  14. GDC-0941 and Cisplatin in Treating Patients With Androgen Receptor-Negative Triple Negative Metastatic Breast Cancer

    Science.gov (United States)

    2017-05-22

    Estrogen Receptor Negative Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast; Triple Negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

  15. Effects of capsaicin, green tea and CH-19 sweet pepper on appetite and energy intake in humans in negative and positive energy balance

    DEFF Research Database (Denmark)

    Reinbach, Helene Christine; Smeets, A.; Martinussen, Torben

    2009-01-01

    Summary Background & aims Bioactive ingredients have been shown to reduce appetite and energy intake. The magnitude of these effects might depend on energy balance why it was investigated how capsaicin, green tea, CH-19 sweet pepper as well as green tea and capsaicin affect appetite and energy...... intake during respectively negative and positive energy balance. Methods 27 subjects were randomized to three weeks of negative and three weeks of positive energy balance during which capsaicin, green tea, CH-19 sweet pepper, capsaicin + green tea or placebo was ingested on ten separate test days while...... the effects on appetite, energy intake, body weight and heart rate were assessed. Results CH-19 sweet pepper and a combination of capsaicin and green tea reduced energy intake during positive energy balance. Capsaicin and green tea suppressed hunger and increased satiety more during negative than during...

  16. Human papillomavirus prevalence and type distribution in 3603 HIV-positive and HIV-negative women in the general population of Tanzania

    DEFF Research Database (Denmark)

    Dartell, Myassa Arkam; Rasch, Vibeke; Kahesa, Crispin

    2012-01-01

    The aim of the Prevention of Cervical Cancer in Tanzania (PROTECT) study is to assess the prevalence of oncogenic human papillomavirus (HPV) and to determine the type distribution among women in the general population according to human immunodeficiency virus (HIV) status, in preparation for a po......The aim of the Prevention of Cervical Cancer in Tanzania (PROTECT) study is to assess the prevalence of oncogenic human papillomavirus (HPV) and to determine the type distribution among women in the general population according to human immunodeficiency virus (HIV) status, in preparation...

  17. Negation and negative concord in romance

    NARCIS (Netherlands)

    Swart, Henriëtte de; Sag, I.A.

    This paper addresses the two interpretations a combination of negative indefinites can get in concord languages like French, namely a concord reading which amounts to a single negation, or a double negation reading. We develop an analysis in a polyadic framework, in which a sequence of

  18. Effects of affective arousal on choice behavior, reward prediction errors, and feedback-related negativities in human reward-based decision making

    Directory of Open Access Journals (Sweden)

    Hong-Hsiang eLiu

    2015-05-01

    Full Text Available Emotional experience has a pervasive impact on choice behavior, but the underlying mechanism remains unclear. Introducing facial-expression primes into a probabilistic learning task, we investigated how affective arousal regulates reward-related choice based on behavioral, model fitting, and feedback-related negativity (FRN data. Sixty-six paid subjects were randomly assigned to the Neutral-Neutral (NN, Angry-Neutral (AN, and Happy-Neutral (HN groups. A total of 960 trials were conducted. Subjects in each group were randomly exposed to half trials of the pre-determined emotional faces and another half of the neutral faces before choosing between two cards drawn from two decks with different assigned reward probabilities. Trial-by-trial data were fit with a standard reinforcement learning model using the Bayesian estimation approach. The temporal dynamics of brain activity were simultaneously recorded and analyzed using event-related potentials. Our analyses revealed that subjects in the NN group gained more reward values than those in the other two groups; they also exhibited comparatively differential estimated model-parameter values for reward prediction errors. Computing the difference wave of FRNs in reward versus non-reward trials, compared to the NN group, we found that subjects in the AN and HN groups had larger General FRNs (i.e., FRNs in no-reward trials minus FRNs in reward trials and Expected FRNs (i.e., FRNs in expected reward-omission trials minus FRNs in expected reward-delivery trials, indicating an interruption in predicting reward. Further, both AN and HN groups appeared to be more sensitive to negative outcomes than the NN group. Collectively, our study suggests that affective arousal negatively regulates reward-related choice, probably through overweighting with negative feedback.

  19. Polemic and Descriptive Negations

    DEFF Research Database (Denmark)

    Horslund, Camilla Søballe

    2011-01-01

    to semantics and pragmatics, negations can be used in three different ways, which gives rise to a typology of three different types of negations: 1) the descriptive negation, 2) the polemic negation, and 3) the meta-linguistic negation (Nølke 1999, 4). This typology illuminates the fact that the negation...... as such may be more or less central to the meaning of the utterance. The present paper investigates the role of morphosyntactic and prosodic prominence as well as register and social setting on the interpretation of negations. It seems plausible to expect that if the negation as such is central to the meaning...... of the utterance (as in polemic negations), the negation will be articulated prominently in order to emphasise this importance. Likewise, if the negation is not central to the meaning of the utterance, it should not be articulated prominently. Moreover, it is plausible to expect descriptive negations to be more...

  20. The PIKfyve–ArPIKfyve–Sac3 triad in human breast cancer: Functional link between elevated Sac3 phosphatase and enhanced proliferation of triple negative cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Ikonomov, Ognian C., E-mail: oikonomo@med.wayne.edu; Filios, Catherine, E-mail: cfilios@med.wayne.edu; Sbrissa, Diego, E-mail: dsbrissa@med.wayne.edu; Chen, Xuequn, E-mail: xchen@med.wayne.edu; Shisheva, Assia, E-mail: ashishev@med.wayne.edu

    2013-10-18

    Highlights: •We assess PAS complex proteins and phosphoinositide levels in breast cancer cells. •Sac3 and ArPIKfyve are markedly elevated in triple-negative breast cancer cells. •Sac3 silencing inhibits proliferation in triple-negative breast cancer cell lines. •Phosphoinositide profiles are altered in breast cancer cells. •This is the first evidence linking high Sac3 with breast cancer cell proliferation. -- Abstract: The phosphoinositide 5-kinase PIKfyve and 5-phosphatase Sac3 are scaffolded by ArPIKfyve in the PIKfyve–ArPIKfyve–Sac3 (PAS) regulatory complex to trigger a unique loop of PtdIns3P–PtdIns(3,5)P{sub 2} synthesis and turnover. Whereas the metabolizing enzymes of the other 3-phosphoinositides have already been implicated in breast cancer, the role of the PAS proteins and the PtdIns3P–PtdIns(3,5)P{sub 2} conversion is unknown. To begin elucidating their roles, in this study we monitored the endogenous levels of the PAS complex proteins in cell lines derived from hormone-receptor positive (MCF7 and T47D) or triple-negative breast cancers (TNBC) (BT20, BT549 and MDA-MB-231) as well as in MCF10A cells derived from non-tumorigenic mastectomy. We report profound upregulation of Sac3 and ArPIKfyve in the triple negative vs. hormone-sensitive breast cancer or non-tumorigenic cells, with BT cell lines showing the highest levels. siRNA-mediated knockdown of Sac3, but not that of PIKfyve, significantly inhibited proliferation of BT20 and BT549 cells. In these cells, knockdown of ArPIKfyve had only a minor effect, consistent with a primary role for Sac3 in TNBC cell proliferation. Intriguingly, steady-state levels of PtdIns(3,5)P{sub 2} in BT20 and T47D cells were similar despite the 6-fold difference in Sac3 levels between these cell lines. However, steady-state levels of PtdIns3P and PtdIns5P, both regulated by the PAS complex, were significantly reduced in BT20 vs. T47D or MCF10A cell lines, consistent with elevated Sac3 affecting directly or

  1. Integrating Positive and Clinical Psychology: Viewing Human Functioning as Continua from Positive to Negative Can Benefit Clinical Assessment, Interventions and Understandings of Resilience

    OpenAIRE

    Johnson, J; Wood, AM

    2017-01-01

    In this review we argue in favour of further integration between the disciplines of positive and clinical psychology. We argue that most of the constructs studied by both positive and clinical psychology exist on continua ranging from positive to negative (e.g., gratitude to ingratitude, anxiety to calmness) and so it is meaningless to speak of one or other field studying the “positive” or the “negative”. However, we highlight historical and cultural factors which have led positive and clinic...

  2. Human serum levels of fetal antigen 1 (FA1/Dlk1) increase with obesity, are negatively associated with insulin sensitivity and modulate inflammation in vitro

    DEFF Research Database (Denmark)

    Chacón, M R; Miranda, M; Jensen, C H

    2008-01-01

    in the context of obesity and insulin sensitivity (S(i)); and n=61 severely obese women before and after bariatric surgery. The response in vitro to FA1 protein on human cell lines of monocytes, preadipocytes and mature adipocytes was studied. MEASUREMENTS: Anthropometrical parameters: body mass index, waist...... levels. In severe obesity, serum levels of FA1 decreased 1.4-fold 6 months after bariatric surgery. In vitro assays with FA1 protein on human monocytes and adipocytes cell lines modified the expression of pro-inflammatory cytokines and adipokines (tumor necrosis factor-alpha (TNFalpha), monocyte...

  3. Examining task-dependencies of different attentional processes as reflected in the P3a and reorienting negativity components of the human event-related brain potential.

    Science.gov (United States)

    Munka, Lutz; Berti, Stefan

    2006-04-03

    Unexpected changes in task-irrelevant auditory stimuli are capable to distract processing of task-relevant visual information. This effect is accompanied by the elicitation of event-related potential (ERP) components associated with attentional orientation, i.e. P3a and reorienting negativity (RON). In the present study we varied the demands of a visual task in order to test whether the RON component -- as an index of attentional reorientation after distraction -- is confined to a semantic task requiring working memory. In two ERP experiments we applied an auditory-visual distraction paradigm in which subjects were instructed to discriminate visual stimuli preceded by a task-irrelevant sound, this being either a standard tone (600 Hz, 88%) or a deviant tone (660 Hz, 12%). The visual stimuli were numbers which had to be judged on basis of a semantic (odd or even) or physical feature (either size or colour). As expected, deviance related ERP components namely the mismatch negativity (MMN), P3a, and RON were elicited. Importantly, the RON was affected by the variation of the task: within the semantic task an early RON and within the physical task a late RON was obtained. These results suggest that the RON component reflects two functionally distinct processes of attentional allocation after distraction: refocusing on task-relevant information on the working memory level, and general reorientation of attention, e.g. preparation for the upcoming task.

  4. Lack of differences in radiation-induced immunogenicity parameters between HPV-positive and HPV-negative human HNSCC cell lines.

    Science.gov (United States)

    Schneider, Karolin; Bol, Vanesa; Grégoire, Vincent

    2017-09-01

    Clinical studies indicate that patients with HPV/p16-associated head & neck squamous cell carcinoma (HNSCC) represent a subgroup with a better prognosis and improved response to conventional radiotherapy. Involvement of immune-based factors has been hypothesized. In the present study, we investigated radiation-induced differences in release of damage associated molecular patterns (DAMPs), cytokines and activation of dendritic cells (DCs) in HPV-positive and negative HNSCC cancer cell lines. Calreticulin (CRT) exposure was detected on cancer cell surface. ATP, HMGB1 and cytokines were measured in culture supernatants. Maturation marker CD83 surface exposure was determined on DCs after co-incubation with irradiated tumor cells. There was no increase in DAMPs and cytokine profiles after radiation treatment and no difference between HPV+ and HPV- cell lines. The HPV/p16-positive SCC90 cells showed a trend for increased total CRT, HMGB1, and number of cytokines compared to all other cell lines. None of the irradiated cancer cell lines could affect DC maturation. Radiation treatment did not increase immunogenicity of HNSCC cell lines assessed by membrane CRT, ATP, HMGB1, cytokines production, and by activation of immature DCs. There was no difference between HPV-positive and HPV-negative cell lines. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Subjective sleepiness correlates negatively with global alpha (8–12 Hz) and positively with central frontal theta (4–8 Hz) frequencies in the human resting awake electroencephalogram

    NARCIS (Netherlands)

    Strijkstra, Arjen M.; Beersma, Domien G.M.; Drayer, Berdine; Halbesma, Nynke; Daan, Serge

    2003-01-01

    Subjective sleepiness is part of the system controlling the decision to go to sleep in humans. Extended periods of waking lead to increased sleepiness, as well as to changes in cortical electroencephalogram (EEG) during waking. We investigated the association of sleepiness and awake EEG spectra

  6. Subjective sleepiness correlates negatively with global alpha (8-12 Hz) and positively with central frontal theta (4-8 Hz) frequencies in the human resting awake electroencephalogram

    NARCIS (Netherlands)

    Strijkstra, AM; Beersma, DGM; Drayer, B; Halbesma, N; Daan, S

    2003-01-01

    Subjective sleepiness is part of the system controlling the decision to go to sleep in humans. Extended periods of waking lead to increased sleepiness, as well as to changes in cortical electroencephalogram (EEG) during waking. We investigated the association of sleepiness and awake EEG spectra

  7. Triple Negative Breast Cancer – An Overview

    OpenAIRE

    Aysola, Kartik; Desai, Akshata; Welch, Crystal; Xu, Jingyao; QIN, YUNLONG; REDDY, VAISHALI; Matthews,Roland; Owens, Charlotte; Okoli, Joel; Beech, Derrick J; Piyathilake, Chandrika J.; Reddy, Shyam P; Rao, Veena N.

    2013-01-01

    Triple Negative Breast Cancer (TNBC) is a heterogeneous disease that based on immunohistochemistry (IHC) is estrogen receptor (ER) negative, progesterone receptor (PR) negative and human epidermal growth factor receptor 2 (HER2) negative. TNBC is typically observed in young AA women and Hispanic women who carry a mutation in the BRCA1 gene. TNBC is characterized by a distinct molecular profile, aggressive nature and lack of targeted therapies. The purpose of this article is to review the curr...

  8. Adjective metaphors evoke negative meanings.

    Science.gov (United States)

    Sakamoto, Maki; Utsumi, Akira

    2014-01-01

    Previous metaphor studies have paid much attention to nominal metaphors and predicative metaphors, but little attention has been given to adjective metaphors. Although some studies have focused on adjective metaphors, they only examined differences in the acceptability of various types of adjective metaphors. This paper explores the cognitive effects evoked by adjective metaphors. Three psychological experiments revealed that (1) adjective metaphors, especially those modified by color adjectives, tend to evoke negative effect; (2) although the meanings of metaphors are basically affected by the meanings of their vehicles, when a vehicle has a neutral meaning, negative meanings are evoked most frequently for adjective metaphors compared to nominal and predicative metaphors; (3) negative meanings evoked by adjective metaphors are related to poeticness, and poetic metaphors evoke negative meanings more easily than less poetic metaphors. Our research sheds new light on studies of the use of metaphor, which is one of the most basic human cognitive abilities.

  9. Adjective metaphors evoke negative meanings.

    Directory of Open Access Journals (Sweden)

    Maki Sakamoto

    Full Text Available Previous metaphor studies have paid much attention to nominal metaphors and predicative metaphors, but little attention has been given to adjective metaphors. Although some studies have focused on adjective metaphors, they only examined differences in the acceptability of various types of adjective metaphors. This paper explores the cognitive effects evoked by adjective metaphors. Three psychological experiments revealed that (1 adjective metaphors, especially those modified by color adjectives, tend to evoke negative effect; (2 although the meanings of metaphors are basically affected by the meanings of their vehicles, when a vehicle has a neutral meaning, negative meanings are evoked most frequently for adjective metaphors compared to nominal and predicative metaphors; (3 negative meanings evoked by adjective metaphors are related to poeticness, and poetic metaphors evoke negative meanings more easily than less poetic metaphors. Our research sheds new light on studies of the use of metaphor, which is one of the most basic human cognitive abilities.

  10. The Modified Human DNA Repair Enzyme O6-Methylguanine-DNA Methyltransferase Is a Negative Regulator of Estrogen Receptor-Mediated Transcription upon Alkylation DNA Damage

    OpenAIRE

    Teo, Alvin K. C.; Oh, Hue Kian; Ali, Rahmen B.; Li, Benjamin F. L.

    2001-01-01

    Cell proliferation requires precise control to prevent mutations from replication of (unrepaired) damaged DNA in cells exposed spontaneously to mutagens. Here we show that the modified human DNA repair enzyme O6-methylguanine-DNA methyltransferase (R-MGMT), formed from the suicidal repair of the mutagenic O6-alkylguanine (6RG) lesions by MGMT in the cells exposed to alkylating carcinogens, functions in such control by preventing the estrogen receptor (ER) from transcription activation that me...

  11. Effect of silver/copper and copper oxide nanoparticle powder on growth of Gram-negative and Gram-positive bacteria and their toxicity against the normal human dermal fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Peszke, Jerzy; Nowak, Anna, E-mail: ana.maria.nowak@gmail.com; Szade, Jacek; Szurko, Agnieszka; Zygadło, Dorota; Michałowska, Marlena [University of Silesia, A. Chelkowski Institute of Physics (Poland); Krzyściak, Paweł [Jagiellonian University Medical College, Department of Mycology Chair of Microbiology (Poland); Zygoń, Patrycja [Czestochowa University of Technology, Institute of Materials Engineering (Poland); Ratuszna, Alicja [University of Silesia, A. Chelkowski Institute of Physics (Poland); Ostafin, Marek M. [Department of Microbiology University of Agriculture (Poland)

    2016-12-15

    Engineered nanomaterials, especially metallic nanoparticles, are the most popular system applied in daily life products. The study of their biological and toxicity properties seems to be indispensable. In this paper, we present results of biological activity of Ag/Cu nanoparticles. These nanoparticles show more promising killing/inhibiting properties on Gram-negative bacteria than for Gram-positive ones. The Gram-negative bacteria show strong effect already at the concentration of 1 ppm after 15 min of incubation. Moreover, in vitro tests of toxicity made on normal human dermal fibroblast cultures showed that after 72 h of incubation with Ag/Cu nanoparticles, they are less toxic then Cu{sub 2}O/CuO nanoparticles.

  12. Effect of silver/copper and copper oxide nanoparticle powder on growth of Gram-negative and Gram-positive bacteria and their toxicity against the normal human dermal fibroblasts

    Science.gov (United States)

    Peszke, Jerzy; Nowak, Anna; Szade, Jacek; Szurko, Agnieszka; Zygadło, Dorota; Michałowska, Marlena; Krzyściak, Paweł; Zygoń, Patrycja; Ratuszna, Alicja; Ostafin, Marek M.

    2016-12-01

    Engineered nanomaterials, especially metallic nanoparticles, are the most popular system applied in daily life products. The study of their biological and toxicity properties seems to be indispensable. In this paper, we present results of biological activity of Ag/Cu nanoparticles. These nanoparticles show more promising killing/inhibiting properties on Gram-negative bacteria than for Gram-positive ones. The Gram-negative bacteria show strong effect already at the concentration of 1 ppm after 15 min of incubation. Moreover, in vitro tests of toxicity made on normal human dermal fibroblast cultures showed that after 72 h of incubation with Ag/Cu nanoparticles, they are less toxic then Cu2O/CuO nanoparticles.

  13. Influence of Arsenic (III, Cadmium (II, Chromium (VI, Mercury (II, and Lead (II Ions on Human Triple Negative Breast Cancer (HCC1806 Cell Cytotoxicity and Cell Viability

    Directory of Open Access Journals (Sweden)

    Tsdale F. Mehari

    2017-01-01

    Full Text Available The hazardous consequences of heavy metal ions (HMIs on human health necessitate the immediate need to probe fundamentally the interactions and cytotoxic effects of HMIs on humans. This study investigated the influence of five toxic HMIs (arsenic (As (III, cadmium (Cd (II, chromium (Cr (VI, mercury (Hg (II, and lead (Pb (II on human TNBC (HCC 1806 cell viability using optical microscopy, trypan blue dye-exclusion assays, and flow cytometry. The TNBC cells were exposed to varying concentrations of HMIs for 24 and 48 hours. We evaluated the influence of the concentrations and duration of HMIs exposure on TNBC cell viability. Light microscopy, cell viability assays, revealed that after 48-hour treatment of TNBC cells with 1 x 10-5 M of As (III, Cd (II, Hg (II, Cr (IV, and Pb (II resulted in cell viabilities of 23%, 34%, 35%, 56%, 91% respectively, suggesting that As (III has the greatest cytotoxicity (77% cell death while Pb (II showed the least (9% cell death. Furthermore, flow cytometry revealed that while Pb (II, As (III and Cr (IV had significant increases in cell death, Hg (II caused a G1 arrest. Together, this study revealed that HMIs cause a differential cytotoxic effect on TNBC cells and suggest that they may have very different genotoxic targets and implications in their mutagenic potential.

  14. Negative indefinites in Afrikaans

    OpenAIRE

    Huddlestone, K.M.

    2010-01-01

    This dissertation is concerned with the syntactic and semantic status of negative indefinites in Afrikaans. The problem posed by negative indefinites is that their interpretation appears to differ across double negation (DN) and negative concord (NC) languages. With respect to negative indefinites, Afrikaans displays features that distinguish it from both typical NC and typical DN languages. Contrary to most NC languages, and similarly to DN languages, standard Afrikaans does not allow negati...

  15. Sexually transmitted diseases in homosexual and bisexual males from a cohort of human immunodeficiency virus negative volunteers (Project Horizonte, Belo Horizonte, Brazil

    Directory of Open Access Journals (Sweden)

    Lignani Jr L

    2000-01-01

    Full Text Available Sexually transmitted diseases (STD are very frequent in the whole world. Males who do not use a condom during their sexual relations are at great risk. We report cases of STD during six months of observation, among homosexual/bisexual males who participate in the Project Horizonte. There were 16 cases of genital warts, 6 cases of human immunodeficiency virus infection, 24 cases of unspecific urethritis, 28 cases of herpes simplex virus infection, 30 cases of syphilis, 58 cases of gonorrhea and 84 cases of pediculosis. We concluded that a condom must be used in all sexual relations and new counseling techniques are needed, to avoid this situation.

  16. Testing the snake-detection hypothesis: larger early posterior negativity in humans to pictures of snakes than to pictures of other reptiles, spiders and slugs.

    Science.gov (United States)

    Van Strien, Jan W; Franken, Ingmar H A; Huijding, Jorg

    2014-01-01

    According to the snake detection hypothesis (Isbell, 2006), fear specifically of snakes may have pushed evolutionary changes in the primate visual system allowing pre-attentional visual detection of fearful stimuli. A previous study demonstrated that snake pictures, when compared to spiders or bird pictures, draw more early attention as reflected by larger early posterior negativity (EPN). Here we report two studies that further tested the snake detection hypothesis. In Study 1, we tested whether the enlarged EPN is specific for snakes or also generalizes to other reptiles. Twenty-four healthy, non-phobic women watched the random rapid serial presentation of snake, crocodile, and turtle pictures. The EPN was scored as the mean activity at occipital electrodes (PO3, O1, Oz, PO4, O2) in the 225-300 ms time window after picture onset. The EPN was significantly larger for snake pictures than for pictures of the other reptiles. In Study 2, we tested whether disgust plays a role in the modulation of the EPN and whether preferential processing of snakes also can be found in men. 12 men and 12 women watched snake, spider, and slug pictures. Both men and women exhibited the largest EPN amplitudes to snake pictures, intermediate amplitudes to spider pictures and the smallest amplitudes to slug pictures. Disgust ratings were not associated with EPN amplitudes. The results replicate previous findings and suggest that ancestral priorities modulate the early capture of visual attention.

  17. Acquisition of negative complement regulators by the saprophyte Leptospira biflexa expressing LigA or LigB confers enhanced survival in human serum.

    Science.gov (United States)

    Castiblanco-Valencia, Mónica M; Fraga, Tatiana R; Breda, Leandro C D; Vasconcellos, Sílvio A; Figueira, Cláudio P; Picardeau, Mathieu; Wunder, Elsio; Ko, Albert I; Barbosa, Angela S; Isaac, Lourdes

    2016-05-01

    Leptospiral immunoglobulin-like (Lig) proteins are surface exposed molecules present in pathogenic but not in saprophytic Leptospira species. We have previously shown that Lig proteins interact with the soluble complement regulators Factor H (FH), FH like-1 (FHL-1), FH related-1 (FHR-1) and C4b Binding Protein (C4BP). In this study, we used the saprophyte L. biflexa serovar Patoc as a surrogate host to address the specific role of LigA and LigB proteins in leptospiral complement evasion. L. biflexa expressing LigA or LigB was able to acquire FH and C4BP. Bound complement regulators retained their cofactor activities of FI in the proteolytic cleavage of C3b and C4b. Moreover, heterologous expression of ligA and ligB genes in the saprophyte L. biflexa enhanced bacterial survival in human serum. Complement deposition on lig-transformed L. biflexa was assessed by flow cytometry analysis. With regard to MAC deposition, L. biflexa expressing LigA or LigB presented an intermediate profile: MAC deposition levels were greater than those found in the pathogenic L. interrogans, but lower than those observed for L. biflexa wildtype. In conclusion, Lig proteins contribute to in vitro control of complement activation on the leptospiral surface, promoting an increased bacterial survival in human serum. Copyright © 2016 European Federation of Immunological Societies. All rights reserved.

  18. Characterization of HJ-PI01 as a novel Pim-2 inhibitor that induces apoptosis and autophagic cell death in triple-negative human breast cancer.

    Science.gov (United States)

    Zhao, Yu-Qian; Yin, Yi-Qiong; Liu, Jie; Wang, Gui-Hua; Huang, Jian; Zhu, Ling-Juan; Wang, Jin-Hui

    2016-09-01

    Pim-2 is a short-lived serine/threonine kinase, which plays a key role in metastasis of breast cancer through persistent activation of STAT3. Although the crystal structure of Pim-2 has been reported, but thus far no specific Pim-2-targeted compounds have been reported. In this study, we identified a novel Pim-2 inhibitor, HJ-PI01, by in silico analysis and experimental validation. The protein-protein interaction (PPI) network, chemical synthesis, molecular docking, and molecular dynamics (MD) simulations were used to design and discover the new Pim-2 inhibitor HJ-PI01. The anti-tumor effects of HJ-PI01 were evaluated in human breast MDA-MB-231, MDA-MB-468, MDA-MB-436, MCF-7 cells in vitro and in MDA-MB-231 xenograft mice, which were treated with HJ-PI01 (40 mg·kg(-1)·d(-1), ig) with or without lienal polypeptide (50 mg·kg(-1)·d(-1), ip) for 10 d. The apoptosis/autophage-inducing mechanisms of HJ-PI01 were elucidated using Western blots, immunoblots, flow cytometry, transmission electron microscopy and fluorescence microscopy. Based on the PrePPI network, the potential partners interacting with Pim-2 in regulating apoptosis (160 protein pairs) and autophagy (47 protein pairs) were identified. Based on the structural characteristics of Pim-2, a total of 15 compounds (HJ-PI01 to HJ-P015) were synthesized, which showed moderate or remarkable anti-proliferative potency in the human breast cancer cell lines tested. The most effective compound HJ-PI01 exerted a robust inhibition on MDA-MB-231 cells compared with chlorpromazine and the pan-Pim inhibitor PI003. Molecular dynamics (MD) simulation revealed that HJ-PI01 had a good binding score with Pim-2. Moreover, HJ-PI01 (300 nmol/L) induced death receptor-dependent and mitochondrial apoptosis as well as autophagic death in MDA-MB-231 cells. In MDA-MB-231 xenograft mice, administration of HJ-PI01 remarkably inhibited the tumor growth and induced tumor cell apoptosis in vivo. Co-administration of HJ-PI01 with lienal

  19. Forkhead box protein O3 transcription factor negatively regulates autophagy in human cancer cells by inhibiting forkhead box protein O1 expression and cytosolic accumulation.

    Directory of Open Access Journals (Sweden)

    Wan Long Zhu

    Full Text Available FoxO proteins are important regulators in cellular metabolism and are recognized to be nodes in multiple signaling pathways, most notably those involving PI3K/AKT and mTOR. FoxO proteins primarily function as transcription factors, but recent study suggests that cytosolic FoxO1 participates in the regulation of autophagy. In the current study, we find that cytosolic FoxO1 indeed stimulates cellular autophagy in multiple cancer cell lines, and that it regulates not only basal autophagy but also that induced by rapamycin and that in response to nutrient deprivation. These findings illustrate the importance of FoxO1 in cell metabolism regulation independent of its transcription factor function. In contrast to FoxO1, we find the closely related FoxO3a is a negative regulator of autophagy in multiple cancer cell lines, a previously unrecognized function for this protein, different from its function in benign fibroblast and muscle cells. The induction of autophagy by the knockdown of FoxO3a was found not to be mediated through the suppression of mTORC1 signaling; rather, the regulatory role of FoxO3a on autophagy was determined to be through its ability to transcriptionally suppress FoxO1. This complicated interplay of FoxO1 and FoxO3a suggests a complex checks- and balances-relationship between FoxO3a and FoxO1 in regulating autophagy and cell metabolism.

  20. Noninvasive 89Zr-Transferrin PET Shows Improved Tumor Targeting Compared with 18F-FDG PET in MYC-Overexpressing Human Triple-Negative Breast Cancer.

    Science.gov (United States)

    Henry, Kelly E; Dilling, Thomas R; Abdel-Atti, Dalya; Edwards, Kimberly J; Evans, Michael J; Lewis, Jason S

    2018-01-01

    The current standard for breast PET imaging is 18F-FDG. The heterogeneity of 18F-FDG uptake in breast cancer limits its utility, varying greatly among receptor status, histopathologic subtypes, and proliferation markers. 18F-FDG PET often exhibits nonspecific internalization and low specificity and sensitivity, especially with tumors smaller than 1 cm3 MYC is a protein involved in oncogenesis and is overexpressed in triple-negative breast cancer (TNBC). Increased surface expression of transferrin receptor (TfR) is a downstream event of MYC upregulation and has been validated as a clinically relevant target for molecular imaging. Transferrin labeled with 89Zr has successfully identified MYC status in many cancer subtypes preclinically and been shown to predict response and changes in oncogene status via treatment with small-molecule inhibitors that target MYC and PI3K signaling pathways. We hypothesized that 89Zr-transferrin PET will noninvasively detect MYC and TfR and improve upon the current standard of 18F-FDG PET for MYC-overexpressing TNBC. Methods: In this study, 89Zr-transferrin and 18F-FDG imaging were compared in preclinical models of TNBC. TNBC cells (MDA-MB-157, MDA-MB-231, and Hs578T) were treated with bromodomain-containing protein 4 (BRD4) inhibitors JQ1 and OTX015 (0.5-1 μM). Cell proliferation, gene expression, and protein expression were assayed to explore the effects of these inhibitors on MYC and TfR. Results: Head-to-head comparison showed that 89Zr-transferrin targets TNBC tumors significantly better (P PET imaging and biodistribution studies in MDA-MB-231 and MDA-MB-157 xenografts and a patient-derived xenograft model of TNBC. c-Myc and TfR gene expression was decreased upon treatment with BRD4 inhibitors and c-MYC small interfering RNA (P PET imaging and biodistribution studies. 89Zr-transferrin is a useful tool to interrogate MYC via TfR-targeted PET imaging in TNBC. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

  1. Negative energy; L'energie negative

    Energy Technology Data Exchange (ETDEWEB)

    Ford, L. [Tufts Univ., Medford, MA (United States); Roman, Th. [Connecticut Univ., Farmington, CT (United States)

    2000-05-01

    We could travel at light velocity or more if we mastered a new form of energy called negative energy. This energy is predicted by the quantum theory and follows from the Heisenberg principle applied to the void. In the void the density of energy is null in average but in fact fluctuates around zero according to the quantum theory, so we can find places with negative energy. This concept has nothing to do with antimatter or with the energy introduced in the recent theories of anti-gravity. According to the theory of general relativity the presence of matter and energy distorts the space-time geometry. In the presence of negative energy strange phenomena might happen. A tunnel could bridge 2 distant points in the universe, and inside it travelling at light velocity or more would be possible. (A.C.)

  2. Does leaching of naturally occurring radionuclides from roadway pavements stabilised with coal fly ash have negative impacts on groundwater quality and human health?

    Science.gov (United States)

    Almahayni, T; Vanhoudt, N

    2018-05-05

    We assessed the potential impact of using coal fly ash to stabilise roadway pavements on groundwater quality and human health. The leaching potential of naturally occurring radionuclides (NORs) typically present in the fly ash was assessed with the HYDRUS-1D code and data representative of a segment of the Wisconsin State Trunk Highway 60 as a case study. Our assessment suggests that the impact would be mainly from the chemical toxicity of uranium (U). In our particular case study, U concentration in the leachate exceeded the maximum contaminant level for this element (MCL = 30 μg L -1 ) in almost all the scenarios. In the groundwater, the MCL was only exceeded under conditions of high leaching and low dilution in the aquifer. The radiological toxicity from the consumption of the contaminated groundwater by a hypothetical adult, however, was at maximum 43% of the individual dose criterion (IDC = 0.1 mSv y -1 ). The results also highlight the need to consider site-specific conditions such as climate and hydrogeology when assessing the environmental impacts of utilising fly ash in roadway construction applications since they could have profound effects on the assessment findings. There is also a pressing need for reliable and representative data to support realistic assessments. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Acquiring negative polarity items

    NARCIS (Netherlands)

    Lin, J.

    2015-01-01

    Negative Polarity Items (NPIs) are words or expressions that exhibit a restricted distribution to certain negative contexts only. For example, yet is an NPI and must appear in the scope of a negation: Mary has *(not) finished yet. The existence of NPIs such as yet gives rise to a learnability

  4. Multicenter phase II study of capecitabine plus cisplatin as first-line therapy for human epidermal growth factor receptor 2-negative advanced gastric cancer: Yokohama Clinical Oncology Group Study YCOG1107.

    Science.gov (United States)

    Sato, Kei; Kunisaki, Chikara; Kosaka, Takashi; Takagawa, Ryo; Takahashi, Masazumi; Izumisawa, Yusuke; Miyamoto, Hiroshi; Sato, Sho; Tanaka, Yusaku; Yamaguchi, Naotaka; Kimura, Jun; Ono, Hidetaka A; Makino, Hirochika; Akiyama, Hirotoshi; Endo, Itaru

    2017-11-01

    S-1 plus cisplatin therapy is the recommended standard first-line regimen for human epidermal growth factor receptor 2 (HER-2)-negative advanced unresectable or recurrent gastric cancer (AGC) in the Japanese Gastric Cancer Treatment Guidelines. By contrast, capecitabine plus cisplatin (XP) therapy has been second-line therapy for these patients. This prospective study aimed to evaluate the efficacy and safety of XP as a first-line regimen for HER2-negative patients with AGC. In this multicenter, open-label, phase II study, patients received cisplatin (80 mg/m2 i.v. day 1) plus capecitabine (1000 mg/m2 orally, twice daily, days 1-14) at 3 week intervals until disease progression or non-continuation for various reasons. The primary endpoint was overall response rate; secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity profiles. Thirty-six patients with HER2-negative AGC were enrolled in this study. Of these, 16 patients with evaluable lesions were assessable for efficacy and 36 were assessable for toxicity. One patient achieved a complete response and five partial responses. The overall response rate was 37.5% [95% confidence interval (CI) 13.7-61.2%] calculated on an intention-to-treat basis. The median PFS and median OS were 5.2 months (95% CI 4.2-6.2 months) and 16.9 months (95% CI 5.8-27.9 months), respectively. Treatment-related adverse events were generally mild; the most common grade 3/4 adverse event was neutropenia (27.8%), followed by anorexia (19.4%), leucopenia (16.7%), anemia (16.7%), and nausea (13.9%). XP as first-line therapy is effective and well tolerated by patients with HER2-negative AGC.

  5. Coagulase-Negative Staphylococci

    Science.gov (United States)

    Heilmann, Christine; Peters, Georg

    2014-01-01

    SUMMARY The definition of the heterogeneous group of coagulase-negative staphylococci (CoNS) is still based on diagnostic procedures that fulfill the clinical need to differentiate between Staphylococcus aureus and those staphylococci classified historically as being less or nonpathogenic. Due to patient- and procedure-related changes, CoNS now represent one of the major nosocomial pathogens, with S. epidermidis and S. haemolyticus being the most significant species. They account substantially for foreign body-related infections and infections in preterm newborns. While S. saprophyticus has been associated with acute urethritis, S. lugdunensis has a unique status, in some aspects resembling S. aureus in causing infectious endocarditis. In addition to CoNS found as food-associated saprophytes, many other CoNS species colonize the skin and mucous membranes of humans and animals and are less frequently involved in clinically manifested infections. This blurred gradation in terms of pathogenicity is reflected by species- and strain-specific virulence factors and the development of different host-defending strategies. Clearly, CoNS possess fewer virulence properties than S. aureus, with a respectively different disease spectrum. In this regard, host susceptibility is much more important. Therapeutically, CoNS are challenging due to the large proportion of methicillin-resistant strains and increasing numbers of isolates with less susceptibility to glycopeptides. PMID:25278577

  6. Placental endoplasmic reticulum stress negatively regulates transcription of placental growth factor via ATF4 and ATF6β: implications for the pathophysiology of human pregnancy complications.

    Science.gov (United States)

    Mizuuchi, Masahito; Cindrova-Davies, Tereza; Olovsson, Matts; Charnock-Jones, D Stephen; Burton, Graham J; Yung, Hong Wa

    2016-03-01

    Low maternal circulating concentrations of placental growth factor (PlGF) are one of the hallmarks of human pregnancy complications, including fetal growth restriction (FGR) and early-onset pre-eclampsia (PE). Currently, PlGF is used clinically with other biomarkers to screen for high-risk cases, although the mechanisms underlying its regulation are largely unknown. Placental endoplasmic reticulum (ER) stress has recently been found to be elevated in cases of FGR, and to an even greater extent in early-onset PE complicated with FGR. ER stress activates the unfolded protein response (UPR); attenuation of protein translation and a reduction in cell growth and proliferation play crucial roles in the pathophysiology of these complications of pregnancy. In this study, we further identified that ER stress regulates release of PlGF. We first observed that down-regulation of PlGF protein was associated with nuclear localization of ATF4, ATF6α and ATF6β in the syncytiotrophoblast of placentae from PE patients. Transcript analysis showed a decrease of PlGF mRNA, and an increase from genes encoding those UPR transcription factors in placentae from cases of early-onset PE, but not of late-onset (>34 weeks) PE, compared to term controls. Further investigations indicated a strong correlation between ATF4 and PlGF mRNA levels only (r = - 0.73, p pregnancy complications. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  7. Inhibition of signaling between human CXCR4 and zebrafish ligands by the small molecule IT1t impairs the formation of triple-negative breast cancer early metastases in a zebrafish xenograft model

    Directory of Open Access Journals (Sweden)

    Claudia Tulotta

    2016-02-01

    Full Text Available Triple-negative breast cancer (TNBC is a highly aggressive and recurrent type of breast carcinoma that is associated with poor patient prognosis. Because of the limited efficacy of current treatments, new therapeutic strategies need to be developed. The CXCR4-CXCL12 chemokine signaling axis guides cell migration in physiological and pathological processes, including breast cancer metastasis. Although targeted therapies to inhibit the CXCR4-CXCL12 axis are under clinical experimentation, still no effective therapeutic approaches have been established to block CXCR4 in TNBC. To unravel the role of the CXCR4-CXCL12 axis in the formation of TNBC early metastases, we used the zebrafish xenograft model. Importantly, we demonstrate that cross-communication between the zebrafish and human ligands and receptors takes place and human tumor cells expressing CXCR4 initiate early metastatic events by sensing zebrafish cognate ligands at the metastatic site. Taking advantage of the conserved intercommunication between human tumor cells and the zebrafish host, we blocked TNBC early metastatic events by chemical and genetic inhibition of CXCR4 signaling. We used IT1t, a potent CXCR4 antagonist, and show for the first time its promising anti-tumor effects. In conclusion, we confirm the validity of the zebrafish as a xenotransplantation model and propose a pharmacological approach to target CXCR4 in TNBC.

  8. Optimizing the treatment of bevacizumab as first-line therapy for human epidermal growth factor receptor 2 (HER2-negative advanced breast cancer: an updated meta-analysis of published randomized trials

    Directory of Open Access Journals (Sweden)

    Li C

    2017-06-01

    Full Text Available Cunfu Li,1 Aizhai Xiang,2 Xianzhi Chen,3 Kai Yin,4 Jinsong Lu,4 Wenjin Yin5,6 1Department of General Surgery, Weihai Central Hospital, Weihai, 2Department of Breast Surgery, Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou, 3Department of General Surgery, Huainan First People’s Hospital, Huainan, 4Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 5Department of Breast Surgery, Fudan University Shanghai Cancer Center, 6Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China Background: Manifold data have demonstrated that the addition of bevacizumab to chemotherapy improved progression-free survival (PFS, while few trials have revealed its significant overall survival (OS benefit. Furthermore, it still remains suspended how to maximize the benefits of bevacizumab as first-line therapy for human epidermal growth factor receptor 2 (HER2-negative breast cancer. We sought to conduct a meta-analysis to assess the benefits of bevacizumab with chemotherapy and to identify the ideal chemotherapy partner of bevacizumab in the first-line setting for HER2-negative advanced breast cancer patients.Methods: Computerized and manual searches were performed to identify randomized clinical trials evaluating the efficacy of bevacizumab plus chemotherapy versus chemotherapy alone or bevacizumab with different chemotherapy regimens as first-line therapy for HER2-negative locally recurrent or metastatic breast cancer patients. Risk ratios or odds ratios with their 95% CIs were used to estimate the association between multiple combinations of bevacizumab with chemotherapy and various clinical outcomes.Results: With 7 trials identified, this analysis included 3,984 eligible patients. The addition of bevacizumab to chemotherapy resulted in a statistically significant improvement in PFS (P=0.019 and objective response rate (ORR; P<0.001 rather than

  9. Negative Ion Density Fronts

    Energy Technology Data Exchange (ETDEWEB)

    Igor Kaganovich

    2000-12-18

    Negative ions tend to stratify in electronegative plasmas with hot electrons (electron temperature Te much larger than ion temperature Ti, Te > Ti ). The boundary separating a plasma containing negative ions, and a plasma, without negative ions, is usually thin, so that the negative ion density falls rapidly to zero-forming a negative ion density front. We review theoretical, experimental and numerical results giving the spatio-temporal evolution of negative ion density fronts during plasma ignition, the steady state, and extinction (afterglow). During plasma ignition, negative ion fronts are the result of the break of smooth plasma density profiles during nonlinear convection. In a steady-state plasma, the fronts are boundary layers with steepening of ion density profiles due to nonlinear convection also. But during plasma extinction, the ion fronts are of a completely different nature. Negative ions diffuse freely in the plasma core (no convection), whereas the negative ion front propagates towards the chamber walls with a nearly constant velocity. The concept of fronts turns out to be very effective in analysis of plasma density profile evolution in strongly non-isothermal plasmas.

  10. Negative Affect in Human Robot Interaction

    DEFF Research Database (Denmark)

    Rehm, Matthias; Krogsager, Anders

    2013-01-01

    The vision of social robotics sees robots moving more and more into unrestricted social environments, where robots interact closely with users in their everyday activities, maybe even establishing relationships with the user over time. In this paper we present a field trial with a robot in a semi...

  11. Freeze or Flee? Negative Stimuli Elicit Selective Responding

    Science.gov (United States)

    Estes, Zachary; Verges, Michelle

    2008-01-01

    Humans preferentially attend to negative stimuli. A consequence of this automatic vigilance for negative valence is that negative words elicit slower responses than neutral or positive words on a host of cognitive tasks. Some researchers have speculated that negative stimuli elicit a general suppression of motor activity, akin to the freezing…

  12. Isotropic Single Negative Metamaterials

    Directory of Open Access Journals (Sweden)

    P. Protiva

    2008-09-01

    Full Text Available This paper presents the application of simple, and therefore cheap, planar resonators for building 3D isotropic metamaterials. These resonators are: a broadside-coupled split ring resonator with a magnetic response providing negative permeability; an electric dipole terminated by a loop inductor together with a double H-shaped resonator with an electric response providing negative permittivity. Two kinds of 3D isotropic single negative metamaterials are reported. The first material consists of unit cells in the form of a cube bearing on its faces six equal planar resonators with tetrahedral symmetry. In the second material, the planar resonators boxed into spherical plastic shells and randomly distributed in a hosting material compose a real 3D volumetric metamaterial with an isotropic response. In both cases the metamaterial shows negative permittivity or permeability, according to the type of resonators that are used. The experiments prove the isotropic behavior of the cells and of the metamaterial specimens.

  13. Meningitis - gram-negative

    Science.gov (United States)

    ... life-threatening illness. Prevention Prompt treatment of related infections may reduce the risk of meningitis. Alternative Names Gram-negative meningitis Images Central nervous system and peripheral nervous ...

  14. Negative labeling and social exclusion of people living with human immunodeficiency virus/acquired immune deficiency syndrome in the antiretroviral therapy era: insight from attitudes and behavioral intentions of female heads of households in Zambézia Province, Mozambique.

    Science.gov (United States)

    Mukolo, Abraham; Blevins, Meridith; Hinton, Nicole; Victor, Bart; Vaz, Lara M E; Sidat, Mohsin; Vergara, Alfredo E

    2014-01-01

    In the age of antiretroviral therapy (ART), unraveling specific aspects of stigma that impede uptake and adherence to human immunodeficiency virus (HIV) services and the complex intersections among them might enhance the efficacy of stigma-reduction interventions targeted at the general public. Few studies have described community stigma in high HIV prevalence regions of Mozambique where program scale-up has been concentrated, but fear of stigma persists as a barrier to HIV service uptake. Principal components analysis of attitudinal data from 3749 female heads of households surveyed in Zambézia Province was used to examine patterns of agreement with stigmatizing attitudes and behavior toward people living with HIV. Inferences were based on comparison of factor loadings and commonality estimates. Construct validity was established through correlations with levels of knowledge about HIV transmission and consistency with the labeling theory of stigma. Two unique domains of community stigma were observed: negative labeling and devaluation (NLD, α = 0.74) and social exclusion (SoE, α = 0.73). NLD is primarily an attitudinal construct, while SoE captures behavioral intent. About one-third of the respondents scored in the upper tertile of the NLD stigma scale (scale: 0-100 stigma points) and the equivalent was 41.3% in the SoE stigma scale. Consistent with literature, NLD and SoE stigma scores were inversely correlated with HIV transmission route knowledge. In item level analysis, fear of being labeled a prostitute/immoral and of negative family affect defined the nature of stigma in this sample. Thus, despite ART scale-up and community education about HIV/acquired immune deficiency syndrome (AIDS), NLD and SoE characterized the community stigma of HIV in this setting. Follow-up studies could compare the impact of these stigma domains on HIV services uptake, in order to inform domain-focused stigma-reduction interventions.

  15. Impact of palbociclib plus letrozole on pain severity and pain interference with daily activities in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer as first-line treatment.

    Science.gov (United States)

    Bell, T; Crown, J P; Lang, I; Bhattacharyya, H; Zanotti, G; Randolph, S; Kim, S; Huang, X; Huang Bartlett, C; Finn, R S; Slamon, D

    2016-05-01

    Background Palbociclib is a recently approved drug for use in combination with letrozole as initial endocrine-based therapy for the treatment of postmenopausal women with advanced estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer. This report assesses the impact of palbociclib in combination with letrozole versus letrozole alone on patient-reported outcomes of pain. Methods Palbociclib was evaluated in an open-label, randomized, phase II study (PALOMA-1/TRIO-18) among postmenopausal women with advanced ER+/HER2- breast cancer who had not received prior systemic treatment for their advanced disease. Patients received continuous oral letrozole 2.5 mg daily alone or the same letrozole dose and schedule plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over repeated 28-day cycles. The primary study endpoint was investigator-assessed progression-free survival in the intent-to-treat population, and these results have recently been published (Finn et al., Lancet Oncol 2015;16:25-35). One of the key secondary endpoints was the evaluation of pain, as measured using the Brief Pain Inventory (BPI) patient-reported outcome tool. The BPI was administered at baseline and on day 1 of every cycle thereafter until disease progression and/or treatment discontinuation. Clinical trial registration This study is registered with ClinicalTrials.gov (NCT00721409). Results There were no statistically significant differences in Pain Severity or Pain Interference scores of the BPI between the two treatment groups for the overall population or among those with any bone disease at baseline. A limitation of the study is that results were not adjusted for the concomitant use of opioids or other medications used to control pain. Conclusions The addition of palbociclib to letrozole was associated with increased efficacy without negatively impacting pain severity or pain interference with daily activities.

  16. A Retrospective Survival Analysis of Anatomic and Prognostic Stage Group Based on the American Joint Committee on Cancer 8th Edition Cancer Staging Manual in Luminal B Human Epidermal Growth Factor Receptor 2-negative Breast Cancer.

    Science.gov (United States)

    Xu, Ling; Li, Jiang-Hong; Ye, Jing-Ming; Duan, Xue-Ning; Cheng, Yuan-Jia; Xin, Ling; Liu, Qian; Zhou, Bin; Liu, Yin-Hua

    2017-08-20

    Current understanding of tumor biology suggests that breast cancer is a group of diseases with different intrinsic molecular subtypes. Anatomic staging system alone is insufficient to provide future outcome information. The American Joint Committee on Cancer (AJCC) expert panel updated the 8th edition of the staging manual with prognostic stage groups by incorporating biomarkers into the anatomic stage groups. In this study, we retrospectively analyzed the data from our center in China using the anatomic and prognostic staging system based on the AJCC 8th edition staging manual. We reviewed the data from January 2008 to December 2014 for cases with Luminal B Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer in our center. All cases were restaged using the AJCC 8th edition anatomic and prognostic staging system. The Kaplan-Meier method and log-rank test were used to compare the survival differences between different subgroups. SPSS software version 19.0 (IBM Corp., Armonk, NY, USA) was used for the statistical analyses. This study consisted of 796 patients with Luminal B HER-negative breast cancer. The 5-year disease-free survival (DFS) of 769 Stage I-III patients was 89.7%, and the 5-year overall survival (OS) of all 796 patients was 91.7%. Both 5-year DFS and 5-year OS were significantly different in the different anatomic and prognostic stage groups. There were 372 cases (46.7%) assigned to a different group. The prognostic Stage II and III patients restaged from anatomic Stage III had significant differences in 5-year DFS (χ2 = 11.319, P= 0.001) and 5-year OS (χ2 = 5.225, P= 0.022). In addition, cases restaged as prognostic Stage I, II, or III from the anatomic Stage II group had statistically significant differences in 5-year DFS (χ2 = 6.510, P= 0.039) but no significant differences in 5-year OS (χ2 = 5.087, P= 0.079). However, the restaged prognostic Stage I and II cases from anatomic Stage I had no statistically significant

  17. NEGATION AFFIXES IN ENGLISH

    Directory of Open Access Journals (Sweden)

    Dedy Subandowo -

    2017-02-01

    Full Text Available Abstract: This research entitled "Negation Affixes in English". This study is aimed to describe the various negation affixes in English, morphological process, morphophonemic and meaning. The research data were taken from various sources of English grammar book, morphology, research journal and the book which relatees to the research. English grammar books used in this study are written by Otto Jesperson, Marcella Frank, Greenbaum and Geoffrey Leech.  The method used in this research is the descriptive-qualitative method. While the data collection techniques are performed by using jot-down method. And the results of analysis are presented in tabular form and descriptive method. The result of the research shows that English has six types of negative affixes which are categorized by the intensity of its appearance, such as dis-, in-, non-, un-, anti- and -less. Based on the function, negation affixes are divided into several categories such as adjectives, nouns, verbs, and adverbs. The morphophonemic affix in- has four allomorphs, they are in-, im-, il- and ir- . While the analysis revealed that negation affixes have some basic meanings, such as ‘not’, ‘without’, and ‘anti’.

  18. Negative reinforcement in applied behavior analysis: an emerging technology.

    OpenAIRE

    Iwata, B A

    1987-01-01

    Although the effects of negative reinforcement on human behavior have been studied for a number of years, a comprehensive body of applied research does not exist at this time. This article describes three aspects of negative reinforcement as it relates to applied behavior analysis: behavior acquired or maintained through negative reinforcement, the treatment of negatively reinforced behavior, and negative reinforcement as therapy. A consideration of research currently being done in these area...

  19. Nedtrykt af negative nyheder

    DEFF Research Database (Denmark)

    Skovsgaard, Morten; Søberg, Pernille Frantz

    2016-01-01

    I adskillige år er det blevet debatteret, hvorvidt nyhedernes negative fokus har konsekvenser for borgerne, og om det i sid-ste ende får flere til at vende ryggen til nyhederne. Vores viden om effekterne af positive og negative nyheder er dog begrænset, og derfor undersøges det i denne artikel......, hvordan henholdsvis positive og negative tv-nyheder påvirker seernes humør, hukom-melse af information fra indslaget og lyst til at se yderligere tv-nyheder. Det gør vi i et survey-eksperiment (N=204), hvor tre grupper så enten et originalt indslag eller det samme indslag klippet med henholdsvis et...

  20. Depressionens negative spiral

    DEFF Research Database (Denmark)

    Munk, Karen

    2006-01-01

    Artiklen formidler resultater fra en longitudinel undersøgelse af det selvforstærkende, negative samspil imellem udvikling og vedligeholdelse af alderdomsdepression via primære miljøbelastninger og via  den deprimerede ældre som belastning for miljøet, som i sin tur "svarer negativt" på lidelsen og...

  1. The direct effect of Focal Adhesion Kinase (FAK, dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis

    Directory of Open Access Journals (Sweden)

    Zhang Li

    2009-08-01

    Full Text Available Abstract Background Focal adhesion kinase (FAK is a non-receptor tyrosine kinase that plays an important role in survival signaling. FAK has been shown to be overexpressed in breast cancer tumors at early stages of tumorigenesis. Methods To study the direct effect of FAK on breast tumorigenesis, we developed Tet-ON (tetracycline-inducible system of MCF-7 breast cancer cells stably transfected with FAK or dominant-negative, C-terminal domain of FAK (FAK-CD, and also FAKsiRNA with silenced FAK MCF-7 stable cell line. Increased expression of FAK in isogenic Tet-inducible MCF-7 cells caused increased cell growth, adhesion and soft agar colony formation in vitro, while expression of dominant-negative FAK inhibitor caused inhibition of these cellular processes. To study the role of induced FAK and FAK-CD in vivo, we inoculated these Tet-inducible cells in nude mice to generate tumors in the presence or absence of doxycycline in the drinking water. FAKsiRNA-MCF-7 cells were also injected into nude mice to generate xenograft tumors. Results Induction of FAK resulted in significant increased tumorigenesis, while induced FAK-CD resulted in decreased tumorigenesis. Taq Man Low Density Array assay demonstrated specific induction of FAKmRNA in MCF-7-Tet-ON-FAK cells. DMP1, encoding cyclin D binding myb-like protein 1 was one of the genes specifically affected by Tet-inducible FAK or FAK-CD in breast xenograft tumors. In addition, silencing of FAK in MCF-7 cells with FAK siRNA caused increased cell rounding, decreased cell viability in vitro and inhibited tumorigenesis in vivo. Importantly, Affymetrix microarray gene profiling analysis using Human Genome U133A GeneChips revealed >4300 genes, known to be involved in apoptosis, cell cycle, and adhesion that were significantly down- or up-regulated (p Conclusion Thus, these data for the first time demonstrate the direct effect of FAK expression and function on MCF-7 breast cancer tumorigenesis in vivo and reveal

  2. Macrophage-derived chemokine and EBI1-ligand chemokine attract human thymocytes in different stage of development and are produced by distinct subsets of medullary epithelial cells: possible implications for negative selection.

    Science.gov (United States)

    Annunziato, F; Romagnani, P; Cosmi, L; Beltrame, C; Steiner, B H; Lazzeri, E; Raport, C J; Galli, G; Manetti, R; Mavilia, C; Vanini, V; Chantry, D; Maggi, E; Romagnani, S

    2000-07-01

    The chemoattractant activity of macrophage-derived chemokine (MDC), EBI1-ligand chemokine (ELC), and secondary lymphoid tissue chemokine (SLC) on human thymocytes was analyzed. Both ELC and SLC caused the accumulation of CD4+CD8- or CD4-CD8+ CD45RA+ thymocytes showing high CD3 expression. By contrast, a remarkable proportion of MDC-responsive thymocytes were CD4+CD8+ cells exhibiting reduced levels of CD8 or CD4+CD8- cells showing CD3 and CD45R0, but not CD45RA. MDC-responsive thymocyte suspensions were enriched in cells expressing the MDC receptor, CCR4, selectively localized to the medulla, and in CD30+ cells, whereas ELC-responsive thymocytes never expressed CD30. Reactivity to both MDC and ELC was localized to cells of the medullary areas, but never in the cortex. Double immunostaining showed no reactivity for either MDC or ELC by T cells, macrophages, or mature dendritic cells, whereas many medullary epithelial cells were reactive to MDC or ELC. However, MDC reactivity was consistently localized to the outer wall of Hassal's corpuscles, whereas ELC reactivity was often found in cells surrounding medullary vessels, but not in Hassal's corpuscles. Moreover, while most MDC-producing cells also stained positive for CD30L, this molecule was never found on ELC-producing cells. We suggest therefore that CD30L-expressing MDC-producing medullary epithelial cells attract CCR4-expressing thymocytes, thus favoring the CD30/CD30L interaction, and therefore the apoptosis, of cells that are induced to express CD30 by autoantigen activation. By contrast, ELC production by CD30L-lacking medullary epithelial cells may induce the migration into periphery of mature thymocytes that have survived the process of negative selection.

  3. Global alteration of the drug-binding pocket of human P-glycoprotein (ABCB1) by substitution of fifteen conserved residues reveals a negative correlation between substrate size and transport efficiency.

    Science.gov (United States)

    Vahedi, Shahrooz; Chufan, Eduardo E; Ambudkar, Suresh V

    2017-11-01

    P-glycoprotein (P-gp), an ATP-dependent efflux pump, is linked to the development of multidrug resistance in cancer cells. However, the drug-binding sites and translocation pathways of this transporter are not yet well-characterized. We recently demonstrated the important role of tyrosine residues in regulating P-gp ATP hydrolysis via hydrogen bond formations with high affinity modulators. Since tyrosine is both a hydrogen bond donor and acceptor, and non-covalent interactions are key in drug transport, in this study we investigated the global effect of enrichment of tyrosine residues in the drug-binding pocket on the drug binding and transport function of P-gp. By employing computational analysis, 15 conserved residues in the drug-binding pocket of human P-gp that interact with substrates were identified and then substituted with tyrosine, including 11 phenylalanine (F72, F303, F314, F336, F732, F759, F770, F938, F942, F983, F994), two leucine (L339, L975), one isoleucine (I306), and one methionine (M949). Characterization of the tyrosine-rich P-gp mutant in HeLa cells demonstrated that this major alteration in the drug-binding pocket by introducing fifteen additional tyrosine residues is well tolerated and has no measurable effect on total or cell surface expression of this mutant. Although the tyrosine-enriched mutant P-gp could transport small to moderate size (transport large (>1000 Daltons) substrates such as NBD-cyclosporine A, Bodipy-paclitaxel and Bodipy-vinblastine was significantly decreased. This was further supported by the physico-chemical characterization of seventeen tested substrates, which revealed a negative correlation between drug transport and molecular size for the tyrosine-enriched P-gp mutant. Published by Elsevier Inc.

  4. Suicide HSVtk gene delivery by neurotensin-polyplex nanoparticles via the bloodstream and GCV Treatment specifically inhibit the growth of human MDA-MB-231 triple negative breast cancer tumors xenografted in athymic mice.

    Directory of Open Access Journals (Sweden)

    Rosa A Castillo-Rodríguez

    Full Text Available The human breast adenocarcinoma cell line MDA-MB-231 has the triple-negative breast cancer (TNBC phenotype, which is an aggressive subtype with no specific treatment. MDA-MB-231 cells express neurotensin receptor type 1 (NTSR1, which makes these cells an attractive target of therapeutic genes that are delivered by the neurotensin (NTS-polyplex nanocarrier via the bloodstream. We addressed the relevance of this strategy for TNBC treatment using NTS-polyplex nanoparticles harboring the herpes simplex virus thymidine kinase (HSVtk suicide gene and its complementary prodrug ganciclovir (GCV. The reporter gene encoding green fluorescent protein (GFP was used as a control. NTS-polyplex successfully transfected both genes in cultured MDA-MB-231 cells. The transfection was demonstrated pharmacologically to be dependent on activation of NTSR1. The expression of HSVtk gene decreased cell viability by 49% (P<0.0001 and induced apoptosis in cultured MDA-MB-231 cells after complementary GCV treatment. In the MDA-MB-231 xenograft model, NTS-polyplex nanoparticles carrying either the HSVtk gene or GFP gene were injected into the tumors or via the bloodstream. Both routes of administration allowed the NTS-polyplex nanoparticles to reach and transfect tumorous cells. HSVtk expression and GCV led to apoptosis, as shown by the presence of cleaved caspase-3 and Apostain immunoreactivity, and significantly inhibited the tumor growth (55-60% (P<0.001. At the end of the experiment, the weight of tumors transfected with the HSVtk gene was 55% less than that of control tumors (P<0.05. The intravenous transfection did not induce apoptosis in peripheral organs. Our results offer a promising gene therapy for TNBC using the NTS-polyplex nanocarrier.

  5. Negative leave balances

    CERN Multimedia

    Human Resources Department

    2005-01-01

    Members of the personnel entitled to annual leave and, where appropriate, saved leave and/or compensatory leave are requested to take note of the new arrangements described below, which were recommended by the Standing Concertation Committee (SCC) at its meeting on 1Â September 2005 and subsequently approved by the Director-General. The changes do not apply to members of the personnel participating in the Progressive Retirement Programme (PRP) or the Part-time Work as a pre-retirement measure, for whom the specific provisions communicated at the time of joining will continue to apply. Â Negative balances in annual leave, saved leave and/or compensatory leave accounts at the end of the leave year (30th September) and on the date on which bonuses are credited to the saved leave account (31st December): Where members of the personnel have a leave account with a negative balance on 30Â September and/or 31Â December, leave will automatically be transferred from one account to another on the relevant dates i...

  6. Negative leave balances

    CERN Multimedia

    Human Resources Department

    2005-01-01

    Members of the personnel entitled to annual leave and, where appropriate, saved leave and/or compensatory leave are requested to take note of the new arrangements described below, which were recommended by the Standing Concertation Committee (SCC) at its meeting on 1 September 2005 and subsequently approved by the Director-General. The changes do not apply to members of the personnel participating in the Progressive Retirement Programme (PRP) or the Part-time Work as a pre-retirement measure, for whom the specific provisions communicated at the time of joining will continue to apply.  Negative balances in annual leave, saved leave and/or compensatory leave accounts at the end of the leave year (30th September) and on the date on which bonuses are credited to the saved leave account (31st December): Where members of the personnel have a leave account with a negative balance on 30 September and/or 31 December, leave will automatically be transferred from one account to another on the relevant dates in or...

  7. Clinicopathological comparison of triple negative breast cancers ...

    African Journals Online (AJOL)

    Key words: Basal subtype, estrogen receptor, hormone receptors, human epidermal growth factor receptor‑2/neu, progesterone receptor, triple negative. Date of Acceptance: 10‑Nov‑2014. Introduction. Breast cancer is by far the most frequent cancer among women worldwide with an estimated 1.38 million new cases of ...

  8. Do `negative' temperatures exist?

    Science.gov (United States)

    Lavenda, B. H.

    1999-06-01

    A modification of the second law is required for a system with a bounded density of states and not the introduction of a `negative' temperature scale. The ascending and descending branches of the entropy versus energy curve describe particle and hole states, having thermal equations of state that are given by the Fermi and logistic distributions, respectively. Conservation of energy requires isentropic states to be isothermal. The effect of adiabatically reversing the field is entirely mechanical because the only difference between the two states is their energies. The laws of large and small numbers, leading to the normal and Poisson approximations, characterize statistically the states of infinite and zero temperatures, respectively. Since the heat capacity also vanishes in the state of maximum disorder, the third law can be generalized in systems with a bounded density of states: the entropy tends to a constant as the temperature tends to either zero or infinity.

  9. A Retrospective Survival Analysis of Anatomic and Prognostic Stage Group Based on the American Joint Committee on Cancer 8th Edition Cancer Staging Manual in Luminal B Human Epidermal Growth Factor Receptor 2-negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ling Xu

    2017-01-01

    Conclusions: The prognostic staging system proposed in the AJCC 8th edition refines the anatomic stage group in Luminal B HER2-negative breast cancer and will lead to a more personalized approach to breast cancer treatment.

  10. Negative legacy of obesity.

    Directory of Open Access Journals (Sweden)

    Kohsuke Shirakawa

    Full Text Available Obesity promotes excessive inflammation, which is associated with senescence-like changes in visceral adipose tissue (VAT and the development of type 2 diabetes (T2DM and cardiovascular diseases. We have reported that a unique population of CD44hi CD62Llo CD4+ T cells that constitutively express PD-1 and CD153 exhibit cellular senescence and cause VAT inflammation by producing large amounts of osteopontin. Weight loss improves glycemic control and reduces cardiovascular disease risk factors, but its long-term effects on cardiovascular events and longevity in obese individuals with T2DM are somewhat disappointing and not well understood. High-fat diet (HFD-fed obese mice were subjected to weight reduction through a switch to a control diet. They lost body weight and visceral fat mass, reaching the same levels as lean mice fed a control diet. However, the VAT of weight reduction mice exhibited denser infiltration of macrophages, which formed more crown-like structures compared to the VAT of obese mice kept on the HFD. Mechanistically, CD153+ PD-1+ CD4+ T cells are long-lived and not easily eliminated, even after weight reduction. Their continued presence maintains a self-sustaining chronic inflammatory loop via production of large amounts of osteopontin. Thus, we concluded that T-cell senescence is essentially a negative legacy effect of obesity.

  11. Negative Expertise: Comparing Differently Tenured Elder Care Nurses' Negative Knowledge

    Science.gov (United States)

    Gartmeier, Martin; Lehtinen, Erno; Gruber, Hans; Heid, Helmut

    2011-01-01

    Negative expertise is conceptualised as the professional's ability to avoid errors during practice due to certain cognitive agencies. In this study, negative knowledge (i.e. knowledge about what is wrong in a certain context and situation) is conceptualised as one such agency. This study compares and investigates the negative knowledge of elder…

  12. Negative Ions in Space.

    Science.gov (United States)

    Millar, Thomas J; Walsh, Catherine; Field, Thomas A

    2017-02-08

    Until a decade ago, the only anion observed to play a prominent role in astrophysics was H - . The bound-free transitions in H - dominate the visible opacity in stars with photospheric temperatures less than 7000 K, including the Sun. The H - anion is also believed to have been critical to the formation of molecular hydrogen in the very early evolution of the Universe. Once H 2 formed, about 500 000 years after the Big Bang, the expanding gas was able to lose internal gravitational energy and collapse to form stellar objects and "protogalaxies", allowing the creation of heavier elements such as C, N, and O through nucleosynthesis. Although astronomers had considered some processes through which anions might form in interstellar clouds and circumstellar envelopes, including the important role that polycyclic aromatic hydrocarbons might play in this, it was the detection in 2006 of rotational line emission from C 6 H - that galvanized a systematic study of the abundance, distribution, and chemistry of anions in the interstellar medium. In 2007, the Cassini mission reported the unexpected detection of anions with mass-to-charge ratios of up to ∼10 000 in the upper atmosphere of Titan; this observation likewise instigated the study of fundamental chemical processes involving negative ions among planetary scientists. In this article, we review the observations of anions in interstellar clouds, circumstellar envelopes, Titan, and cometary comae. We then discuss a number of processes by which anions can be created and destroyed in these environments. The derivation of accurate rate coefficients for these processes is an essential input for the chemical kinetic modeling that is necessary to fully extract physics from the observational data. We discuss such models, along with their successes and failings, and finish with an outlook on the future.

  13. The clinical effectiveness of individual behaviour change interventions to reduce risky sexual behaviour after a negative human immunodeficiency virus test in men who have sex with men: systematic and realist reviews and intervention development.

    Science.gov (United States)

    Flowers, Paul; Wu, Olivia; Lorimer, Karen; Ahmed, Bipasha; Hesselgreaves, Hannah; MacDonald, Jennifer; Cayless, Sandi; Hutchinson, Sharon; Elliott, Lawrie; Sullivan, Ann; Clutterbuck, Dan; Rayment, Michael; McDaid, Lisa

    2017-01-01

    Men who have sex with men (MSM) experience significant inequalities in health and well-being. They are the group in the UK at the highest risk of acquiring a human immunodeficiency virus (HIV) infection. Guidance relating to both HIV infection prevention, in general, and individual-level behaviour change interventions, in particular, is very limited. To conduct an evidence synthesis of the clinical effectiveness of behaviour change interventions to reduce risky sexual behaviour among MSM after a negative HIV infection test. To identify effective components within interventions in reducing HIV risk-related behaviours and develop a candidate intervention. To host expert events addressing the implementation and optimisation of a candidate intervention. All major electronic databases (British Education Index, BioMed Central, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Educational Resource Index and Abstracts, Health and Medical Complete, MEDLINE, PsycARTICLES, PsycINFO, PubMed and Social Science Citation Index) were searched between January 2000 and December 2014. A systematic review of the clinical effectiveness of individual behaviour change interventions was conducted. Interventions were examined using the behaviour change technique (BCT) taxonomy, theory coding assessment, mode of delivery and proximity to HIV infection testing. Data were summarised in narrative review and, when appropriate, meta-analysis was carried out. Supplemental analyses for the development of the candidate intervention focused on post hoc realist review method, the assessment of the sequential delivery and content of intervention components, and the social and historical context of primary studies. Expert panels reviewed the candidate intervention for issues of implementation and optimisation. Overall, trials included in this review (n = 10) demonstrated that individual-level behaviour change interventions are effective in reducing key HIV infection risk

  14. Dreptul omului de a fi protejat de stresul negativ excesiv – un nou drept fundamental al omului postmodern, la începutul sec. XXI (The right to be protected from the negative stress – a new fundamental right of the post-modern human, at the begining of the XXIst century

    Directory of Open Access Journals (Sweden)

    Mădălina Virginia ANTONESCU

    2015-12-01

    Full Text Available The development of the human rights field, at the beginning of XXIst century, brings new challenges for the legal academic school under the pressure to realize a continuous effort to adapt itself to multiple changes of the global world and equally, to those changes resulted from the state and non-state entities actions, under the impact of specific threats and problems. Within this context, we propose in this paper “a right of human being to be protected from stress -the negative excessive stress-“; in our opinion, this right can be considered, from the beginning, to belong to the IVth generation of human rights, after the category of solidarity rights. Particularly, we consider that it should be adopted (under the aegis of UN.GA a “Charter for the human rigths protection of the metropolitan man”, facing the situations and conditions of life generating a level of stress that is an exclusive feature of the metropolitan style of life, an action prescribed in order to rise concretely the level of protection for human rights, face to challenges brought by postmodern lifestyle. This Charter would realize a consecration of human rights starting from a specific quality of human being (as “living into great urban agglomerations”- metropolis, megalopolis, and by taking into account the universality of the urbanization phenomena, as specific phenomena of the global age, at the beginning of the XXIst century. Quality of the human being “to live into great urban agglomerations” should be taken, in our opinion, into consideration, more attentively, by the XXIst century legal academic school, this quality shifting towards a legal quality, and generating rights and obligations specific to the human being of the XXIst century global society. Also, it should be recommended to ellaborate (possibly, through a Romanian proposal within UN.GA a declaration, signed by UN states, regarding an international day of fighting against negative excessive

  15. Lactic Acid Bacteria Inducing a Weak Interleukin-12 and Tumor Necrosis Alpha Response in Human Dendritic Cells Inhibit Strongly Stimulating Lactic Acid Bacteria but Act Synergistically with Gram-Negative Bacteria

    DEFF Research Database (Denmark)

    Zeuthen, Louise Hjerrild; Christensen, Hanne Risager; Frøkiær, Hanne

    2006-01-01

    The development and maintenance of immune homeostasis indispensably depend on signals from the gut flora. Lactic acid bacteria (LAB), which are gram-positive (G+) organisms, are plausible significant players and have received much attention. Gram-negative (G-) commensals, such as members of the f...

  16. Animal Reasoning: Negation and Representations of Absence.

    Directory of Open Access Journals (Sweden)

    Morales Ladrón de Guevara, Jorge

    2011-05-01

    Full Text Available In this paper I reject the possibility that animal reasoning, negation in particular, necessarily involves the representation of Absence, as suggested by José Luis Bermúdez, since this would still work as a logical negation (unavailable for non-linguistic creatures. False belief, pretense, and communication experiments show that non-human animals (at least some primates have difficulties representing absent entities or properties. I offer an alternative account resorting to the sub-symbolic similarity judgments proposed by Vigo & Allen and I introduce the notion of expectation: animal proto-negation takes place through the incompatibility between an expected and the actual representation. Finally, I propose that the paradigm of expectations can be extrapolated to other experiments in cognitive psychology (both with pre-linguistic children and animals in order to design “fair” experiments which test other minds considering their true abilities.

  17. The case for negative senescence

    DEFF Research Database (Denmark)

    Vaupel, James W; Baudisch, Annette; Dölling, Martin

    2004-01-01

    Negative senescence is characterized by a decline in mortality with age after reproductive maturity, generally accompanied by an increase in fecundity. Hamilton (1966) ruled out negative senescence: we adumbrate the deficiencies of his model. We review empirical studies of various plants and some...... kinds of animals that may experience negative senescence and conclude that negative senescence may be widespread, especially in indeterminate-growth species for which size and fertility increase with age. We develop optimization models of life-history strategies that demonstrate that negative senescence...

  18. Negative Attitudes, Network and Education

    DEFF Research Database (Denmark)

    Bennett, Patrick; la Cour, Lisbeth; Larsen, Birthe

    We consider the impact of negative attitudes against immigrants and immigration on educational choice in a search and wage bargaining model including networking. We consider two cases in terms of the importance of negative attitudes againts immigrants for high and low educated individuals and find...... that more negative attitudes against immigrants has a positive impact on education in one case and a negative impact in the other and has no impact on natives. Immigration improves employment perspectives for immigrants and thereby increases immigrant education whereas endogenous negative attitudes lead...... to an ambiguous impact. Empirically, we consider immigrants’ high school attendance. On the macro-level, we confirm a signficant negative correlation between negative attitudes towards immigrants and high school attendance and a positive impact of networking on high school attendance. On the individual level, we...

  19. Negative snakes in JET: evidence for negative shear

    Energy Technology Data Exchange (ETDEWEB)

    Gill, R.D.; Alper, B.; Edwards, A.W. [Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking; Pearson, D. [Reading Univ. (United Kingdom)

    1994-07-01

    The signature of the negative snakes from the soft X-ray cameras is very similar to the more usual snakes except that the localised region of the snake has, compared with its surroundings, decreased rather than increased emission. Circumstances where negative snakes have been seen are reviewed. The negative snake appears as a region of increased resistance and of increased impurity density. The relationship between the shear and the current perturbation is shown, and it seem probable that the magnetic shear is reversed at the point of the negative snake, i.e. that q is decreasing with radius. 6 refs., 6 figs.

  20. Wages, Amenities and Negative Attitudes

    DEFF Research Database (Denmark)

    Waisman, Gisela; Larsen, Birthe

    We exploit the regional variation in negative attitudes towards immigrants to Sweden in order to analyse the consequences of the attitudes on immigrants welfare. We find that attitudes towards immigrants are of importance: they both affect their labour market outcomes and their quality of life. W...... interpret the negative effect on wages as evidence of labour market discrimination. We estimate the welfare effects of negative attitudes, through their wage and local amenities, for immigrants with different levels of skills, origin, gender and age....

  1. Prestarlike functions with negative coefficients

    Directory of Open Access Journals (Sweden)

    H. Silverman

    1979-01-01

    Full Text Available The extreme points for prestarlike functions having negative coefficients are determined. Coefficient, distortion and radii of univalence, starlikeness, and convexity theorems are also obtained.

  2. Income, Amenities and Negative Attitudes

    DEFF Research Database (Denmark)

    Waisman, Gisela; Larsen, Birthe

    2016-01-01

    We exploit the regional variation in negative attitudes towards immigrants to Sweden in order to analyse the consequences of negative attitudes on refugees’ utility from labour income and amenities. We find that attitudes towards immigrants are important: while they affect mainly the refugees......’ quality of life, they also affect their income. We estimate the utility effects of negative attitudes for refugees with different levels of education and gender. We also analyse how the size of the refugees’ networks relate to their quality of life and income as well as how negative attitudes towards...

  3. Causality, Nonlocality, and Negative Refraction.

    Science.gov (United States)

    Forcella, Davide; Prada, Claire; Carminati, Rémi

    2017-03-31

    The importance of spatial nonlocality in the description of negative refraction in electromagnetic materials has been put forward recently. We develop a theory of negative refraction in homogeneous and isotropic media, based on first principles, and that includes nonlocality in its full generality. The theory shows that both dissipation and spatial nonlocality are necessary conditions for the existence of negative refraction. It also provides a sufficient condition in materials with weak spatial nonlocality. These fundamental results should have broad implications in the theoretical and practical analyses of negative refraction of electromagnetic and other kinds of waves.

  4. Negative supervisionsoplevelser og deres konsekvenser

    DEFF Research Database (Denmark)

    Nielsen, Jan

    2011-01-01

    in evaluation. First part of the paper explores negative experience in supervision in general. The second part, focusing on negative experience in supervision caused by evaluation, is explored and discussed in relation to the key concept of supervisory alliance (Bordin, 1983), perceiving evaluation...

  5. Research priorities for negative emissions

    NARCIS (Netherlands)

    Fuss, S.; Jones, C. D.; Kraxner, F.; Peters, G. P.; Smith, P.; Tavoni, M.; van Vuuren, Detlef|info:eu-repo/dai/nl/11522016X; Canadell, J. G.; Jackson, R. B.; Milne, J.; Moreira, J. R.; Nakicenovic, N.; Sharifi, A.; Yamagata, Y.

    2016-01-01

    Carbon dioxide removal from the atmosphere (CDR) - also known as 'negative emissions' - features prominently in most 2 °C scenarios and has been under increased scrutiny by scientists, citizens, and policymakers. Critics argue that 'negative emission technologies' (NETs) are insufficiently mature to

  6. The polymorphic insertion of the luteinizing hormone receptor “insLQ” show a negative association to LHR gene expression and to the follicular fluid hormonal profile in human small antral follicles

    DEFF Research Database (Denmark)

    Borgbo, T.; Chrudimska, J.; Macek, M.

    2018-01-01

    The luteinizing hormone receptor (LHCGR) has a little studied polymorphic 6 bp insertion (rs4539842/insLQ). This study has evaluated the insLQ polymorphism in relation to potential associations with hormonal characteristics of human small antral follicles (hSAFs). In total, 310 hSAFs were collected...

  7. Differential expression of DNA topoisomerase II alpha and -beta in P-gp and MRP-negative VM26, mAMSA and mitoxantrone-resistant sublines of the human SCLC cell line GLC(4)

    NARCIS (Netherlands)

    Withoff, S; deVries, EGE; Keith, WN; Nienhuis, EF; vanderGraaf, WTA; Uges, DRA; Mulder, NH

    1996-01-01

    Sublines of the human small-cell lung carcinoma (SCLC) cell line GLC(4) with acquired resistance to teniposide, amsacrine and mitoxantrone (GLC(4)/VM(20x), GLC(4)/AM(3x) and GLC(4)/MIT(60x), respectively) were derived to study the contribution of DNA topoisomerase II alpha and -beta (TopuII alpha

  8. TOPICAL REVIEW: Negative thermal expansion

    Science.gov (United States)

    Barrera, G. D.; Bruno, J. A. O.; Barron, T. H. K.; Allan, N. L.

    2005-02-01

    There has been substantial renewed interest in negative thermal expansion following the discovery that cubic ZrW2O8 contracts over a temperature range in excess of 1000 K. Substances of many different kinds show negative thermal expansion, especially at low temperatures. In this article we review the underlying thermodynamics, emphasizing the roles of thermal stress and elasticity. We also discuss vibrational and non-vibrational mechanisms operating on the atomic scale that are responsible for negative expansion, both isotropic and anisotropic, in a wide range of materials.

  9. Negative Attitudes, Network and Education

    DEFF Research Database (Denmark)

    Bennett, Patrick; la Cour, Lisbeth; Larsen, Birthe

    This paper explores potential explanations behind the educational gap between young natives and immigrants using two measures, negative attitudes towards immigrants and networking, which may influence natives and immigrants differently. The paper considers, both theoretically and empirically......, the impact of negative attitudes and networking taking into account that these parameters may influence high and uneducated workers as well as immigrants and natives differently, creating different incentives to acquire education for the two ethnic groups. Using rich Danish administrative data, this paper...... finds evidence that greater negative attitudes increase incentives for males to acquire education and that networking also increases immigrant education....

  10. Negative-strand RNA viruses: The plant-infecting counterparts

    NARCIS (Netherlands)

    Kormelink, R.J.M.; Garcia, M.L.; Goodin, M.; Sasaya, T.; Haenni, A.L.

    2011-01-01

    While a large number of negative-strand (-)RNA viruses infect animals and humans, a relative small number have plants as their primary host. Some of these have been classified within families together with animal/human infecting viruses due to similarities in particle morphology and genome

  11. The clinicopathologic characteristics and prognostic significance of triple-negativity in node-negative breast cancer

    Science.gov (United States)

    Rhee, Jiyoung; Han, Sae-Won; Oh, Do-Youn; Kim, Jee Hyun; Im, Seock-Ah; Han, Wonshik; Ae Park, In; Noh, Dong-Young; Bang, Yung-Jue; Kim, Tae-You

    2008-01-01

    Background Triple-negative (TN) breast cancer, which is defined as being negative for the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER-2), represents a subset of breast cancer with different biologic behaviour. We investigated the clinicopathologic characteristics and prognostic indicators of lymph node-negative TN breast cancer. Methods Medical records were reviewed from patients with node-negative breast cancer who underwent curative surgery at Seoul National University Hospital between Jan. 2000 and Jun. 2003. Clinicopathologic variables and clinical outcomes were evaluated. Results Among 683 patients included, 136 had TN breast cancer and 529 had non-TN breast cancer. TN breast cancer correlated with younger age (< 35 y, p = 0.003), and higher histologic and nuclear grade (p < 0.001). It also correlated with a molecular profile associated with biological aggressiveness: negative for bcl-2 expression (p < 0.001), positive for the epidermal growth factor receptor (p = 0.003), and a high level of p53 (p < 0.001) and Ki67 expression (p < 0.00). The relapse rates during the follow-up period (median, 56.8 months) were 14.7% for TN breast cancer and 6.6% for non-TN breast cancer (p = 0.004). Relapse free survival (RFS) was significantly shorter among patients with TN breast cancer compared with those with non-TN breast cancer (4-year RFS rate 85.5% vs. 94.2%, respectively; p = 0.001). On multivariate analysis, young age, close resection margin, and triple-negativity were independent predictors of shorter RFS. Conclusion TN breast cancer had higher relapse rate and more aggressive clinicopathologic characteristics than non-TN in node-negative breast cancer. Thus, TN breast cancer should be integrated into the risk factor analysis for node-negative breast cancer. PMID:18947390

  12. Negative magnetic relaxation in superconductors

    Directory of Open Access Journals (Sweden)

    Krasnoperov E.P.

    2013-01-01

    Full Text Available It was observed that the trapped magnetic moment of HTS tablets or annuli increases in time (negative relaxation if they are not completely magnetized by a pulsed magnetic field. It is shown, in the framework of the Bean critical-state model, that the radial temperature gradient appearing in tablets or annuli during a pulsed field magnetization can explain the negative magnetic relaxation in the superconductor.

  13. Use of Negation in Search

    Science.gov (United States)

    2010-06-01

    as of May 2010, produced a large number of images of Volkswagen Beetles as shown in Figure 8. After indicating they were ready to proceed... Volkswagen 1 beetle -VW -car 1 beetle –car - Volkswagen 1 beetle -VW - Volkswagen 1 beetle -VW -car - Volkswagen 1 black beetle Not within first 30...that had many Volkswagen Beetles in the results, why did you choose not to use negation?] 9. [Do you think that negation would have been useful in

  14. Negative Attitudes, Networks and Education

    DEFF Research Database (Denmark)

    Bennett, Patrick; la Cour, Lisbeth; Larsen, Birthe

    This paper theoretically and empirically assesses the potential explanations behind the educational gap between young natives and immigrants using two measures, negative attitudes towards immigrants and networking. The paper considers that two these parameters may influence high and uneducated...... workers as well as immigrants and natives differently, creating different incentives to acquire education for the two groups. Using rich Danish administrative data, this paper finds suggestive evidence rejecting the theoretical case where negative attitudes decrease 1st generation immigrant education...

  15. Gramsci between Machiavelli and Marx: from negative determination of human to ontonegative determination of politics Gramsci entre Maquiavel e Marx: da negatividade do homem a ontonegatividade da política

    Directory of Open Access Journals (Sweden)

    Claudinei Cássio Rezende

    2008-12-01

    Full Text Available In one of his central categories, Gramsci establishes a connection between the Machiavellian and Marxian political conceptions, in a manner that each one writes to the revolutionary class of their time. Nevertheless, a more rigorous critic at Marx’s propositions unveils to us that the proletarian class isn’t just the progressist class of his time, in the same manner that the bourgeois was in the Iluminism, like Gramsci thinks, but it is, actually, the universal sphere and the only one qualifi ed to accomplish a human emancipation. Consequently, the connection between Machiavelli and Marx does not exist, once Marx conceives the ontological work as the central attribute of humanization, and conceives the politics as temporary; while Machiavelli conceives the politics as the founder act of all sociability. Keywords: Machiavelli. Marx. Gramsci. Ontonegative determination of politics. Human emancipation. Em uma de suas categorias centrais, Gramsci estabelece uma identidade direta entre as politicidades maquiaveliana e marxiana, de sorte que cada um escreve para a classe da vanguarda política de sua época. No entanto, uma crítica mais rigorosa aos escritos marxianos nos revela que o proletariado não é somente a classe progressista de sua época, da maneira que a burguesia fora no iluminismo, como quer Gramsci, mas é, em verdade, a esfera universal e a única capaz de levar a cabo uma emancipação humana total. Doravante, a identidade entre Marx e Maquiavel inexiste na medida em que o primeiro, de magnitude filosófica distinta, concebe o trabalho ontologicamente como atributo central da humanização, apreendendo a política como uma figura transitória superável, enquanto o segundo concebe a política como o ato fundador de toda sociabilidade. Palavras-chave: Maquiavel. Marx. Gramsci. Ontonegatividade da política. Emancipação humana.

  16. Genetic Susceptibility to Triple Negative Breast Cancer

    OpenAIRE

    Stevens, Kristen N.; Vachon, Celine M.; Couch, Fergus J.

    2013-01-01

    Triple negative breast cancers (TNBC), defined by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression, account for 12-24% of all breast cancers. TNBC is associated with early recurrence of disease and poor outcome. Germline mutations in the BRCA1 and BRCA2 breast cancer susceptibility genes have been associated with up to 15% of TNBC, and TNBC accounts for 70% of breast tumors arising in BRCA1 mutation carriers and 16-23% of breast ...

  17. Differences in sensory processing of German vowels and physically matched non-speech sounds as revealed by the mismatch negativity (MMN) of the human event-related brain potential (ERP).

    Science.gov (United States)

    Christmann, Corinna A; Berti, Stefan; Steinbrink, Claudia; Lachmann, Thomas

    2014-09-01

    We compared processing of speech and non-speech by means of the mismatch negativity (MMN). For this purpose, the MMN elicited by vowels was compared to those elicited by two non-speech stimulus types: spectrally rotated vowels, having the same stimulus complexity as the speech stimuli, and sounds based on the bands of formants of the vowels, representing non-speech stimuli of lower complexity as compared to the other stimulus types. This design allows controlling for effects of stimulus complexity when comparing neural correlates of processing speech to non-speech. Deviants within a modified multi-feature design differed either in duration or spectral property. Moreover, the difficulty to discriminate between the standard and the two deviants was controlled for each stimulus type by means of an additional active discrimination task. Vowels elicited a larger MMN compared to both non-speech stimulus types, supporting the concept of language-specific phoneme representations and the role of the participants' prior experience. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. The Prevalence of Human Immunodeficiency Virus Infection among Pregnant Women in Labour with Unknown Status and those with Negative Status Early in the Index Pregnancy in a Tertiary Hospital in Nigeria.

    Science.gov (United States)

    Ukaire, Binyerem C; Agboghoroma, Chris O; Durojaiye, Korede W

    2015-09-01

    Rapid HIV test in labour provide an opportunity for the identification of HIV positive pregnant women who should benefit from interventions to reduce the risk of mother-to-child transmission (MTCT) of HIV. Between November 2013 and June 2014 we conducted rapid HIV testing of pregnant women in labour at the National Hospital Abuja to determine the HIV seroconversion rate in pregnancy and the prevalence of HIV in pregnant women in labour with previously unknown status. HIV testing and counseling (HTC) was acceptable to 224 (99.6%) of the pregnant women who met the study criteria. The mean 'turnaround' time for test result was 288 minutes and 16.2 minutes for tests performed in the hospital laboratory and those performed at the point-of-care (labour ward) respectively. HIV seroconversion was detected in 2(1.2%) of the 165 parturients with initial HIV negative result early in the index pregnancy. HIV infection was detected in four (2.7%) of the 59 parturients with unknown HIV status. Secondary school level education was significantly associated with HIV seroconversion in pregnancy P labour using rapid testing strategy is feasible and acceptable in our setting. The introduction of HCT will lead to the diagnosis of HIV positive women in labour, appropriate interventions and prevention of MTCT of HIV.

  19. Characterization of CaV1.2 exon 33 heterozygous knockout mice and negative correlation between Rbfox1 and CaV1.2 exon 33 expressions in human heart failure.

    Science.gov (United States)

    Wang, Juejin; Li, Guang; Yu, Dejie; Wong, Yuk Peng; Yong, Tan Fong; Liang, Mui Cheng; Liao, Ping; Foo, Roger; Hoppe, Uta C; Soong, Tuck Wah

    2017-09-26

    Recently, we reported that homozygous deletion of alternative exon 33 of CaV1.2 calcium channel in the mouse resulted in ventricular arrhythmias arising from increased CaV1.2Δ33 ICaL current density in the cardiomyocytes. We wondered whether heterozygous deletion of exon 33 might produce cardiac phenotype in a dose-dependent manner, and whether the expression levels of RNA splicing factors known to regulate alternative splicing of exon 33 might change in human heart failure. Unexpectedly, we found that exon 33+/- cardiomyocytes showed similar CaV1.2 channel properties as wild-type cardiomyocyte, even though CaV1.2Δ33 channels exhibit a gain-in-function. In human hearts, we found that the mRNA level of splicing factor Rbfox1, but not Rbfox2, was downregulated in dilated cardiomyopathy, and CACNA1C mRNA level was dramatically decreased in the both of dilated and ischemic cardiomyopathy. These data imply Rbfox1 may be involved in the development of cardiomyopathies via regulating the alternative splicing of CaV1.2 exon 33. (149 words).

  20. Bayesian network model of crowd emotion and negative behavior

    Science.gov (United States)

    Ramli, Nurulhuda; Ghani, Noraida Abdul; Hatta, Zulkarnain Ahmad; Hashim, Intan Hashimah Mohd; Sulong, Jasni; Mahudin, Nor Diana Mohd; Rahman, Shukran Abd; Saad, Zarina Mat

    2014-12-01

    The effects of overcrowding have become a major concern for event organizers. One aspect of this concern has been the idea that overcrowding can enhance the occurrence of serious incidents during events. As one of the largest Muslim religious gathering attended by pilgrims from all over the world, Hajj has become extremely overcrowded with many incidents being reported. The purpose of this study is to analyze the nature of human emotion and negative behavior resulting from overcrowding during Hajj events from data gathered in Malaysian Hajj Experience Survey in 2013. The sample comprised of 147 Malaysian pilgrims (70 males and 77 females). Utilizing a probabilistic model called Bayesian network, this paper models the dependence structure between different emotions and negative behaviors of pilgrims in the crowd. The model included the following variables of emotion: negative, negative comfortable, positive, positive comfortable and positive spiritual and variables of negative behaviors; aggressive and hazardous acts. The study demonstrated that emotions of negative, negative comfortable, positive spiritual and positive emotion have a direct influence on aggressive behavior whereas emotion of negative comfortable, positive spiritual and positive have a direct influence on hazardous acts behavior. The sensitivity analysis showed that a low level of negative and negative comfortable emotions leads to a lower level of aggressive and hazardous behavior. Findings of the study can be further improved to identify the exact cause and risk factors of crowd-related incidents in preventing crowd disasters during the mass gathering events.

  1. The negation bias: When negations signal stereotypic expectancies

    NARCIS (Netherlands)

    Beukeboom, C.J.; Finkenauer, C.; Wigboldus, D.H.J.

    2010-01-01

    Research on linguistic biases shows that stereotypic expectancies are implicitly reflected in language and are thereby subtly communicated to message recipients. We examined whether these findings extend to the use of negations (e.g., not smart instead of stupid). We hypothesized that people use

  2. Ultrasonic metamaterials with negative modulus.

    Science.gov (United States)

    Fang, Nicholas; Xi, Dongjuan; Xu, Jianyi; Ambati, Muralidhar; Srituravanich, Werayut; Sun, Cheng; Zhang, Xiang

    2006-06-01

    The emergence of artificially designed subwavelength electromagnetic materials, denoted metamaterials, has significantly broadened the range of material responses found in nature. However, the acoustic analogue to electromagnetic metamaterials has, so far, not been investigated. We report a new class of ultrasonic metamaterials consisting of an array of subwavelength Helmholtz resonators with designed acoustic inductance and capacitance. These materials have an effective dynamic modulus with negative values near the resonance frequency. As a result, these ultrasonic metamaterials can convey acoustic waves with a group velocity antiparallel to phase velocity, as observed experimentally. On the basis of homogenized-media theory, we calculated the dispersion and transmission, which agrees well with experiments near 30 kHz. As the negative dynamic modulus leads to a richness of surface states with very large wavevectors, this new class of acoustic metamaterials may offer interesting applications, such as acoustic negative refraction and superlensing below the diffraction limit.

  3. Sigma Models with Negative Curvature

    CERN Document Server

    Alonso, Rodrigo; Manohar, Aneesh V.

    2016-01-01

    We construct Higgs Effective Field Theory (HEFT) based on the scalar manifold H^n, which is a hyperbolic space of constant negative curvature. The Lagrangian has a non-compact O(n,1) global symmetry group, but it gives a unitary theory as long as only a compact subgroup of the global symmetry is gauged. Whether the HEFT manifold has positive or negative curvature can be tested by measuring the S-parameter, and the cross sections for longitudinal gauge boson and Higgs boson scattering, since the curvature (including its sign) determines deviations from Standard Model values.

  4. Incisional Negative Pressure Wound Therapy

    DEFF Research Database (Denmark)

    Hyldig, Nana; Birke-Sorensen, Hanne; Kruse, Marie

    Aim: Postoperative wound complications make many surgical procedures unnecessarily complex, particularly in high-risk patients. Negative Pressure Wound Therapy is well recognized in the management of open wounds. In recent years, it has been introduced as well in the management of closed surgical...... incisions to reduce postoperative wound complications, though the evidence base to support this intervention is limited. The aim of this study was to assess if Negative Pressure Wound Therapy (NPWT) reduces postoperative complications when applied on closed surgical incisions. Method: A systematic review...

  5. Antrodia salmonea induces G2 cell-cycle arrest in human triple-negative breast cancer (MDA-MB-231) cells and suppresses tumor growth in athymic nude mice.

    Science.gov (United States)

    Chang, Chia-Ting; Hseu, You-Cheng; Thiyagarajan, Varadharajan; Huang, Hui-Chi; Hsu, Li-Sung; Huang, Pei-Jane; Liu, Jer-Yuh; Liao, Jiunn-Wang; Yang, Hsin-Ling

    2017-01-20

    Antrodia salmonea (AS), is a well-known folk medicinal mushroom in Taiwan, has been reported to exhibit anti-oxidant, anti-angiogenic, and anti-inflammatory effects. In the present study, we examined the effects of AS on cell-cycle arrest in vitro in MDA-MB-231 cells and on tumor regression in vivo using an athymic nude mice model. AS (0-200μg/mL) treatment significantly induced G2 cell-cycle arrest in MDA-MB-231 cells by reducing the levels of cyclin B1, cyclin A, cyclin E, and CDC2 proteins. In addition, N-acetylcysteine (NAC) pretreatment prevented AS induced G2 cell-cycle arrest, indicating that ROS accumulation and subsequent cell cycle arrest might be a major mechanism of AS-induced cytotoxicity. Further, AS treatment decreased COX-2 expression and induced PARP cleavage was significantly reversed by NAC pretreatment in MDA-MB-231 cells. The in vivo study results revealed that AS treatment was effective in terms of delaying the tumor incidence and reducing the tumor growth in MDA-MB-231-xenografted nude mice. TUNEL assay, immunohistochemical staining and Western blotting confirmed that AS significantly modulated the xenografted tumor progression as demonstrated by induction of apoptosis, autophagy, and cell-cycle arrest. Our data strongly suggest that Antrodia salmonea could be an anti-cancer agent for human breast cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Veillonella, Firmicutes: Microbes disguised as Gram negatives.

    Science.gov (United States)

    Vesth, Tammi; Ozen, Aslı; Andersen, Sandra C; Kaas, Rolf Sommer; Lukjancenko, Oksana; Bohlin, Jon; Nookaew, Intawat; Wassenaar, Trudy M; Ussery, David W

    2013-12-20

    The Firmicutes represent a major component of the intestinal microflora. The intestinal Firmicutes are a large, diverse group of organisms, many of which are poorly characterized due to their anaerobic growth requirements. Although most Firmicutes are Gram positive, members of the class Negativicutes, including the genus Veillonella, stain Gram negative. Veillonella are among the most abundant organisms of the oral and intestinal microflora of animals and humans, in spite of being strict anaerobes. In this work, the genomes of 24 Negativicutes, including eight Veillonella spp., are compared to 20 other Firmicutes genomes; a further 101 prokaryotic genomes were included, covering 26 phyla. Thus a total of 145 prokaryotic genomes were analyzed by various methods to investigate the apparent conflict of the Veillonella Gram stain and their taxonomic position within the Firmicutes. Comparison of the genome sequences confirms that the Negativicutes are distantly related to Clostridium spp., based on 16S rRNA, complete genomic DNA sequences, and a consensus tree based on conserved proteins. The genus Veillonella is relatively homogeneous: inter-genus pair-wise comparison identifies at least 1,350 shared proteins, although less than half of these are found in any given Clostridium genome. Only 27 proteins are found conserved in all analyzed prokaryote genomes. Veillonella has distinct metabolic properties, and significant similarities to genomes of Proteobacteria are not detected, with the exception of a shared LPS biosynthesis pathway. The clade within the class Negativicutes to which the genus Veillonella belongs exhibits unique properties, most of which are in common with Gram-positives and some with Gram negatives. They are only distantly related to Clostridia, but are even less closely related to Gram-negative species. Though the Negativicutes stain Gram-negative and possess two membranes, the genome and proteome analysis presented here confirm their place within the

  7. Incisional Negative Pressure Wound Therapy

    DEFF Research Database (Denmark)

    Hyldig, Nana; Vinter, Christina Anne; Bille, Camilla

    Background: Obese women undergoing caesarean section are at increased risk of surgical wound complications, which may lead to delayed recovery, pain, reduced quality of life, and increased health care cost. The aim of this study is to evaluate the effect of incisional Negative Pressure Wound...

  8. NEGATIVE IMPLANT - A RETROSPECTIVE STUDY

    NARCIS (Netherlands)

    LANDESZ, M; WORST, JGF; SIERTSEMA, JV; VANRIJ, G

    1993-01-01

    Implantation of a negative power intraocular lens is one of the options for surgical correction of high myopia. We studied 36 eyes with a Fechner Worst Claw Lens, implanted in Groningen between March 1987 and November 1991. The preoperative myopia ranged from -7.00 to -30.00 diopters. Twentyone eyes

  9. Counterfactual success and negative freedom

    NARCIS (Netherlands)

    Dowding, K; van Hees, M.V.B.P.M

    Recent theories of negative freedom see it as a value-neutral concept; the definition of freedom should not be in terms of specific moral values. Specifically, preferences or desires do not enter into the definition of freedom. If preferences should so enter then Berlin's problem that a person may

  10. Focusing on the Negative: Cultural Differences in Expressions of Sympathy

    Science.gov (United States)

    Koopmann-Holm, Birgit; Tsai, Jeanne L.

    2014-01-01

    Feeling concern about the suffering of others is considered a basic human response, and yet, we know surprisingly little about the cultural factors that shape how people respond to the suffering of another person. To this end, we conducted four studies that tested the hypothesis that American expressions of sympathy focus on the negative less and positive more than German expressions of sympathy, in part because Americans want to avoid negative states more than Germans do. In Study 1, we demonstrate that American sympathy cards contained less negative and more positive content than German sympathy cards. In Study 2, we show that European Americans want to avoid negative states more than Germans do. In Study 3, we demonstrate that these cultural differences in “avoided negative affect” mediate cultural differences in how comfortable Americans and Germans felt focusing on the negative (vs. positive) when expressing sympathy for the hypothetical death of an acquaintance's father. To examine whether greater avoided negative affect results in lesser focus on the negative and greater focus on the positive when responding to another person's suffering, in Study 4, American and German participants were randomly assigned to one of two conditions: (1) to “push negative images away” (i.e., increasing desire to avoid negative affect), or (2) to “pull negative images closer” to themselves (i.e., decreasing desire to avoid negative affect). Participants were then asked to pick a card to send to an acquaintance whose father had hypothetically just died. Across cultures, participants in the “push negative away” condition were less likely to choose sympathy cards with negative (vs. positive) content than were those in the “pull negative closer” condition. Together, these studies suggest that cultures differ in their desire to avoid negative affect, and that these differences influence the degree to which expressions of sympathy focus on the negative (vs

  11. A Semantic Analysis of Negative Concord

    NARCIS (Netherlands)

    Wouden van der, Ton; Zwarts, Frans

    1993-01-01

    It is not uncommon in natural languages that negation seems to behave in an illogical manner. The general term for the many cases where multiple occurrences of morphologically negative constituents express a single semantic negation is negative concord (Labov 1979). Negative concord may take either

  12. Negation switching invariant signed graphs

    Directory of Open Access Journals (Sweden)

    Deepa Sinha

    2014-04-01

    Full Text Available A signed graph (or, $sigraph$ in short is a graph G in which each edge x carries a value $\\sigma(x \\in \\{-, +\\}$ called its sign. Given a sigraph S, the negation $\\eta(S$ of the sigraph S is a sigraph obtained from S by reversing the sign of every edge of S. Two sigraphs $S_{1}$ and $S_{2}$ on the same underlying graph are switching equivalent if it is possible to assign signs `+' (`plus' or `-' (`minus' to vertices of $S_{1}$ such that by reversing the sign of each of its edges that has received opposite signs at its ends, one obtains $S_{2}$. In this paper, we characterize sigraphs which are negation switching invariant and also see for what sigraphs, S and $\\eta (S$ are signed isomorphic.

  13. Incisional Negative Pressure Wound Therapy

    DEFF Research Database (Denmark)

    Hyldig, Nana

    the rate of surgical wound infection and wound exudate post-caesarean and that wound infection had a negative impact on quality of life one month after surgery. Alongside the clinical trial, a trial-based cost-effectiveness analysis demonstrated that the treatment is cost-effective in a high......Women with a pre-gestational body mass index (BMI) above 30 kg/m2 giving birth by caesarean section are at high risk of surgical wound infection compared with women with a BMI below 30 kg/m2. Incisional Negative Pressure Wound Therapy (iNPWT) is one strategy to reduce the rate of surgical wound...... infection. However, the treatment is relatively costly compared to standard postoperative dressings and thus it was important to consider the rationale for using iNPWT before introducing the treatment in a clinical setting. This thesis assesses the current evidence of whether iNPWT reduces post...

  14. Proclus’ View about Negative Theology

    Directory of Open Access Journals (Sweden)

    S Rahimiyan

    2012-09-01

    Full Text Available Negative theology is a modern theological approach that idiomatically implies those theological doctrines which are based on the negative premises and concepts for describing God. Among Greeks, this approach was on its climax in Neo-Platonism. Proclus is one of the Neo-Platonists who lived in fifth century (A.D and was in charge of Athena academy for years. He was the most important Neo-Platonist after Plotinus. In his philosophical system, on the one hand, it is impossible to recognize the first source and, on the other hand, the existence of some principles like the relationship between the creator and the universe, reversion and the way of emanation receiving, requires the knowledge of the first source. It seems that such paradox can be resolved by separating the stages of existence order.

  15. Gram-Negative Flagella Glycosylation

    Directory of Open Access Journals (Sweden)

    Susana Merino

    2014-02-01

    Full Text Available Protein glycosylation had been considered as an eccentricity of a few bacteria. However, through advances in analytical methods and genome sequencing, it is now established that bacteria possess both N-linked and O-linked glycosylation pathways. Both glycosylation pathways can modify multiple proteins, flagellins from Archaea and Eubacteria being one of these. Flagella O-glycosylation has been demonstrated in many polar flagellins from Gram-negative bacteria and in only the Gram-positive genera Clostridium and Listeria. Furthermore, O-glycosylation has also been demonstrated in a limited number of lateral flagellins. In this work, we revised the current advances in flagellar glycosylation from Gram-negative bacteria, focusing on the structural diversity of glycans, the O-linked pathway and the biological function of flagella glycosylation.

  16. Triple-negative breast cancer

    OpenAIRE

    Chacón, Reinaldo D; Costanzo, María V

    2010-01-01

    Perou's molecular classification defines tumors that neither express hormone receptors nor overexpress HER2 as triple-negative (TN) tumors. These tumors account for approximately 15% of breast cancers. The so-called basaloid tumors are not always synonymous with TN tumors; they differ in the fact that they express different molecular markers, have a higher histologic grade, and have a worse prognosis. Clinically they occur in younger women as interval cancer, and the risk of recurrence is hig...

  17. Research priorities for negative emissions

    Science.gov (United States)

    Fuss, S.; Jones, C. D.; Kraxner, F.; Peters, G. P.; Smith, P.; Tavoni, M.; van Vuuren, D. P.; Canadell, J. G.; Jackson, R. B.; Milne, J.; Moreira, J. R.; Nakicenovic, N.; Sharifi, A.; Yamagata, Y.

    2016-11-01

    Carbon dioxide removal from the atmosphere (CDR)—also known as ‘negative emissions’—features prominently in most 2 °C scenarios and has been under increased scrutiny by scientists, citizens, and policymakers. Critics argue that ‘negative emission technologies’ (NETs) are insufficiently mature to rely on them for climate stabilization. Some even argue that 2 °C is no longer feasible or might have unacceptable social and environmental costs. Nonetheless, the Paris Agreement endorsed an aspirational goal of limiting global warming to even lower levels, arguing that climate impacts—especially for vulnerable nations such as small island states—will be unacceptably severe in a 2 °C world. While there are few pathways to 2 °C that do not rely on negative emissions, 1.5 °C scenarios are barely conceivable without them. Building on previous assessments of NETs, we identify some urgent research needs to provide a more complete picture for reaching ambitious climate targets, and the role that NETs can play in reaching them.

  18. Human bites - self-care

    Science.gov (United States)

    Bites - human - self-care ... Human bites can occur in 2 ways: If someone bites you If your hand comes into contact ... bite to express anger or other negative feelings. Human bites may be more dangerous than animal bites. ...

  19. Nosewitness identification: effects of negative emotion.

    Directory of Open Access Journals (Sweden)

    Laura Alho

    Full Text Available Every individual has a unique body odor (BO, similar to a fingerprint. In forensic research, identification of culprit BOs has been performed by trained dogs, but not by humans. We introduce the concept of nosewitness identification and present the first experimental results on BO memory in witness situations involving violent crimes. Two experiments indicated that BO associated with male characters in authentic videos could later be identified in BO lineup tests well above chance. Moreover, culprit BO in emotional crime videos could be identified considerably better than the BO of a male person in neutral videos. This indicates that nosewitness identification benefits from emotional encoding. Altogether, the study testifies to the virtue of body odor as a cue to identify individuals observed under negative emotion.

  20. LINGO-1 negatively regulates myelination by oligodendrocytes.

    Science.gov (United States)

    Mi, Sha; Miller, Robert H; Lee, Xinhua; Scott, Martin L; Shulag-Morskaya, Svetlane; Shao, Zhaohui; Chang, Jufang; Thill, Greg; Levesque, Melissa; Zhang, Mingdi; Hession, Cathy; Sah, Dinah; Trapp, Bruce; He, Zhigang; Jung, Vincent; McCoy, John M; Pepinsky, R Blake

    2005-06-01

    The control of myelination by oligodendrocytes in the CNS is poorly understood. Here we show that LINGO-1 is an important negative regulator of this critical process. LINGO-1 is expressed in oligodendrocytes. Attenuation of its function by dominant-negative LINGO-1, LINGO-1 RNA-mediated interference (RNAi) or soluble human LINGO-1 (LINGO-1-Fc) leads to differentiation and increased myelination competence. Attenuation of LINGO-1 results in downregulation of RhoA activity, which has been implicated in oligodendrocyte differentiation. Conversely, overexpression of LINGO-1 leads to activation of RhoA and inhibition of oligodendrocyte differentiation and myelination. Treatment of oligodendrocyte and neuron cocultures with LINGO-1-Fc resulted in highly developed myelinated axons that have internodes and well-defined nodes of Ranvier. The contribution of LINGO-1 to myelination was verified in vivo through the analysis of LINGO-1 knockout mice. The ability to recapitulate CNS myelination in vitro using LINGO-1 antagonists and the in vivo effects seen in the LINGO-1 knockout indicate that LINGO-1 signaling may be critical for CNS myelination.

  1. EFFECTS OF MEDICAL DISPUTES ON INTERNET COMMUNICATIONS OF NEGATIVE EMOTIONS AND NEGATIVE ONLINE WORD-OF-MOUTH.

    Science.gov (United States)

    Lee, Yi-Chih; Wu, Wei-Li

    2015-08-01

    Emotions play an important role in human behavior. Negative emotions resulting from medical disputes are problems for medical personnel to solve but also have a significant impact on a hospital's reputation and people's trust in the hospital. One medical dispute case was chosen from an Internet news source to assess the correlation between people's negative emotions and negative online word-of-mouth. Convenience sampling was used in school faculties and university students who had shared their medical treatment experiences online were the research participants. A total of 221 Taiwanese participants volunteered (158 women, 63 men; ages: 26.7% under 19, 22.6% 20-29, 30.8% 30-39,19.9% over 40). Four negative emotions were measured using rating scales: uncertainty, anger, disappointment, and sadness. Four negative online word-of-mouth measures were: venting, advice search, helping receiver, and revenge. A modeled relationship was assessed by partial least square method (PLS). Then, people's positive emotions were further analyzed to assess changes after spreading negative word-of-mouth. The results showed that uncertainty had a positive effect on venting and advice search. People who felt anger or regret spread word-of-mouth in order to help the receiver. Disappointment may trigger the revenge behavior of negative word-of-mouth. Negative emotions could be relieved after engaging in the behavior of helping the receiver.

  2. Superluminal travel requires negative energies

    OpenAIRE

    Olum, Ken D.

    1998-01-01

    I investigate the relationship between faster-than-light travel and weak-energy-condition violation, i.e., negative energy densities. In a general spacetime it is difficult to define faster-than-light travel, and I give an example of a metric which appears to allow superluminal travel, but in fact is just flat space. To avoid such difficulties, I propose a definition of superluminal travel which requires that the path to be traveled reach a destination surface at an earlier time than any neig...

  3. Low prevalence of antibiotic-resistant gram-negative bacteria ...

    African Journals Online (AJOL)

    The objective of this study was to determine antibiotic resistance patterns and specific resistance genes in Gram-negative enteric bacteria recovered from 42 different drinking water sources servicing 2 rural villages in south-western Uganda. These water sites were prone to contamination by both human and cattle activity.

  4. Positive and negative reinforcement activate human auditory cortex

    Directory of Open Access Journals (Sweden)

    Tina eWeis

    2013-12-01

    Full Text Available Prior studies suggest that reward modulates neural activity in sensory cortices, but less is known about punishment. We used functional magnetic resonance imaging and an auditory discrimination task, where participants had to judge the duration of frequency modulated tones. In one session correct performance resulted in financial gains at the end of the trial, in a second session incorrect performance resulted in financial loss. Incorrect performance in the rewarded as well as correct performance in the punishment condition resulted in a neutral outcome. The size of gains and losses was either low or high (10 or 50 Euro cent depending on the direction of frequency modulation. We analyzed neural activity at the end of the trial, during reinforcement, and found increased neural activity in auditory cortex when gaining a financial reward as compared to gaining no reward and when avoiding financial loss as compared to receiving a financial loss. This was independent on the size of gains and losses. A similar pattern of neural activity for both gaining a reward and avoiding a loss was also seen in right middle temporal gyrus, bilateral insula and pre-supplemental motor area, here however neural activity was lower after correct responses compared to incorrect responses. To summarize, this study shows that the activation of sensory cortices, as previously shown for gaining a reward is also seen during avoiding a loss.

  5. The Immoral Assumption Effect: Moralization Drives Negative Trait Attributions.

    Science.gov (United States)

    Meindl, Peter; Johnson, Kate M; Graham, Jesse

    2016-04-01

    Jumping to negative conclusions about other people's traits is judged as morally bad by many people. Despite this, across six experiments (total N = 2,151), we find that multiple types of moral evaluations--even evaluations related to open-mindedness, tolerance, and compassion--play a causal role in these potentially pernicious trait assumptions. Our results also indicate that moralization affects negative-but not positive-trait assumptions, and that the effect of morality on negative assumptions cannot be explained merely by people's general (nonmoral) preferences or other factors that distinguish moral and nonmoral traits, such as controllability or desirability. Together, these results suggest that one of the more destructive human tendencies--making negative assumptions about others--can be caused by the better angels of our nature. © 2016 by the Society for Personality and Social Psychology, Inc.

  6. The most important questions in cancer research and clinical oncology : Question 1. Could the vertical transmission of human papilloma virus (HPV) infection account for the cause, characteristics, and epidemiology of HPV-positive oropharyngeal carcinoma, non-smoking East Asian female lung adenocarcinoma, and/or East Asian triple-negative breast carcinoma?

    Science.gov (United States)

    Wee, Joseph T S; Poh, Sharon Shuxian

    2017-01-16

    Specific research foci: (1) Mouse models of gamma-herpes virus-68 (γHV-68) and polyomavirus (PyV) infections during neonatal versus adult life. (2) For human papilloma virus (HPV)-positive oropharyngeal carcinoma (OPC)-(a) Asking the question: Is oral sex a powerful carcinogen? (b) Examining the evidence for the vertical transmission of HPV infection. (c) Examining the relationship between HPV and Epstein-Barr virus (EBV) infections and nasopharyngeal cancer (NPC) in West European, East European, and East Asian countries. (d) Examining the association between HPV-positive OPC and human leukocyte antigen (HLA). (3) For non-smoking East Asian female lung adenocarcinoma-(a) Examining the incidence trends of HPV-positive OPC and female lung adenocarcinoma according to birth cohorts. (b) Examining the association between female lung adenocarcinoma and HPV. (c) Examining the associations of lung adenocarcinoma with immune modulating factors. (4) For triple-negative breast carcinoma (TNBC) in East Asians-(a) Examining the association between TNBC and HPV. (b) Examining the unique epidemiological characteristics of patients with TNBC. A summary "epidemiological" model tying some of these findings together.

  7. Some Phenomena on Negative Inversion Constructions

    Science.gov (United States)

    Sung, Tae-Soo

    2013-01-01

    We examine the characteristics of NDI (negative degree inversion) and its relation with other inversion phenomena such as SVI (subject-verb inversion) and SAI (subject-auxiliary inversion). The negative element in the NDI construction may be" not," a negative adverbial, or a negative verb. In this respect, NDI has similar licensing…

  8. Mondialization: The negation of territory

    Directory of Open Access Journals (Sweden)

    Đorđević Dejan

    2007-01-01

    Full Text Available The main objective of this paper is to present some weaknesses and inconsistence of the mondialization/globalization concept, especially regarding obvious negation of territoriality as a principle and a crude reality of uneven spatial distribution of resources, wealth and population on global scale. The domination of the globalism and neo-liberalism in the spheres of economy, society, culture and even language leads toward greater differences, in such intensity that some authors describe it as a "clash of civilizations". Loosing territoriality means loosing "raison d’etre" of spatial planning. Some efforts to introduce participation as a planning solution for the beginning of the new century is actually a Trojan horse and a step in the wrong direction.

  9. Congenital nystagmus and negative electroretinography

    Directory of Open Access Journals (Sweden)

    Roussi M

    2011-04-01

    Full Text Available Mirella Roussi, Hélène Dalens, Jean Jacques Marcellier, Franck BacinDepartment of Ophthalmology, Clermont-Ferrand University, Clermont-Ferrand, FranceAbstract: Congenital nystagmus is a pathologic oculomotor state appearing at about three to four months of age. The precise diagnosis requires detailed clinical examination and electrophysiological findings. This case report presents two male patients with congenital nystagmus examined longitudinally from the age of six months until 17-18 years of age. Clinical and electrophysiological protocols were detailed. The first results showed electronegative electroretinography in the two cases and examination combined with electroretinographic findings helped us to make the diagnosis of Congenital Night Stationary Blindness (CSNB. This diagnosis was confirmed by genetic studies. CSNB is interesting to study because through electrophysiological findings, it enables a better understanding of the physiology of neural transmission in the outer part of the retina.Keywords: Congenital nystagmus, negative electroretinography, congenital night stationary blindness

  10. NEGATIVE EFFECT OF METALLOID STRESS ON WHEAT

    Directory of Open Access Journals (Sweden)

    Marína Maglovski

    2015-02-01

    Full Text Available Arsenic (As belongs to heavy metals and its accumulation in plants, besides damaging the organism itself, represents a potential health risk to animal and human consumers. Therefore, contamination of soils and waters with this compound is a serious environmental problem. In this work we focused on investigating a negative impact of As on selected parameters of growth of wheat plants (Triticum aestivum L. cv. Genoveva grown in hydropony. In the stage of first assimilation leaves we applied a solution of heavy metal (1 mg.kg-1 As3+ on wheat plants. For plants grown under hydropony conditions we observed different plant parameters such as length, weight, amount of fresh and dry biomass. Further we analyzed accumulation of hydrogen peroxide and products membrane lipid peroxidation as indicators of oxidative stress. In addition to these we also measured the content of photosynthetic pigments, maximal quantum yield and proline in plant tissue. Our data indicate reduction of the biomass of shoots forthcoming as a result of exposure of stressed plants to As. Decline of biomass accumulation was accompanied by increase of hydrogen peroxide in plant tissue. In contrast, level of lipid peroxidation was suppressed in stressed shoots. Contents of photosynthetic pigments soundly decreased. Interestingly, fluorescence (Fp=Fm in stressed wheat shoots increased. Similarly in tested shoots the content of proline was increased. The results indicate that the applied dose of As has a negative impact on the growth and photosynthetic performance of stressed plants. A better understanding of the mechanisms responsible for As resistance and toxicity in plants requires further investigation.

  11. Update on Aire and thymic negative selection.

    Science.gov (United States)

    Passos, Geraldo A; Speck-Hernandez, Cesar A; Assis, Amanda F; Mendes-da-Cruz, Daniella A

    2018-01-01

    Twenty years ago, the autoimmune regulator (Aire) gene was associated with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, and was cloned and sequenced. Its importance goes beyond its abstract link with human autoimmune disease. Aire identification opened new perspectives to better understand the molecular basis of central tolerance and self-non-self distinction, the main properties of the immune system. Since 1997, a growing number of immunologists and molecular geneticists have made important discoveries about the function of Aire, which is essentially a pleiotropic gene. Aire is one of the functional markers in medullary thymic epithelial cells (mTECs), controlling their differentiation and expression of peripheral tissue antigens (PTAs), mTEC-thymocyte adhesion and the expression of microRNAs, among other functions. With Aire, the immunological tolerance became even more apparent from the molecular genetics point of view. Currently, mTECs represent the most unusual cells because they express almost the entire functional genome but still maintain their identity. Due to the enormous diversity of PTAs, this uncommon gene expression pattern was termed promiscuous gene expression, the interpretation of which is essentially immunological - i.e. it is related to self-representation in the thymus. Therefore, this knowledge is strongly linked to the negative selection of autoreactive thymocytes. In this update, we focus on the most relevant results of Aire as a transcriptional and post-transcriptional controller of PTAs in mTECs, its mechanism of action, and its influence on the negative selection of autoreactive thymocytes as the bases of the induction of central tolerance and prevention of autoimmune diseases. © 2017 John Wiley & Sons Ltd.

  12. NEGATIVE PRESSURE WOUND THERAPY (NPWT) FOR THE ...

    African Journals Online (AJOL)

    NEGATIVE PRESSURE WOUND THERAPY (NPWT) FOR THE MANAGEMENT OF LAPAROSTOMY WOUNDS: ... Negative pressure wound therapy (NPWT) is one of the new additions to the armamentarium of laparostomy wound management to achieve the above (8). ... However, second day post operatively she.

  13. Reversing a Negative Measurement in Process with Negative Events: A Haunted Negative Measurement and the Bifurcation of Time

    CERN Document Server

    Snyder, D M

    2003-01-01

    Reversing an ordinary measurement in process (a haunted measurement) is noted and the steps involved in reversing a negative measurement in process (a haunted negative measurement) are described. In order to discuss in a thorough manner reversing an ordinary measurement in process, one has to account for how reversing a negative measurement in process would work for the same experimental setup. The reason it is necessary to know how a negative measurement in process is reversed is because for a given experimental setup there is no physical distinction between reversing a negative measurement in process and reversing an ordinary measurement in process. In the absence of the reversal of a negative measurement in process in the same experimental setup that supports the reversal of an ordinary measurement in process, the possibility exists of which-way information concerning the negative measurement that would render theoretically implausible reversing an ordinary measuremnt in process. The steps in reversing a n...

  14. Emphatic multiple negative expressions in Dutch

    NARCIS (Netherlands)

    Zeijlstra, H.

    2010-01-01

    Double Negation languages like Dutch and German still exhibit constructions, such as Dutch 'niemand niet' ‘nobody not’ or 'nooit geen' ‘nothing no’, that seem to have a Negative Concord reading. Since these constructions normally have an emphatic reading, they are called Emphatic Multiple Negative

  15. Hyperbolic spaces are of strictly negative type

    DEFF Research Database (Denmark)

    Hjorth, Poul G.; Kokkendorff, Simon L.; Markvorsen, Steen

    2002-01-01

    We study finite metric spaces with elements picked from, and distances consistent with, ambient Riemannian manifolds. The concepts of negative type and strictly negative type are reviewed, and the conjecture that hyperbolic spaces are of strictly negative type is settled, in the affirmative...

  16. Frontal negativity: An electrophysiological index of interpersonal guilt.

    Science.gov (United States)

    Leng, Bingbing; Wang, Xiangling; Cao, Bihua; Li, Fuhong

    2017-12-01

    The present study aimed to reveal the temporal course and electrophysiological correlates of interpersonal guilt. Human participants were asked to perform multiple rounds of a dot-estimation task with their partners, while event-related potential being recorded. The paired participants were informed that they would win money if both responded correctly; otherwise, both of them would lose money. The feeling of guilt in Self-Wrong condition (SW) was significantly higher than that in Both-Wrong and Partner-Wrong conditions. At approximately 350 ms after the onset of feedback presentation, greater negativities were observed in the frontal regions in the guilt condition (i.e., SW) than those in the non-guilt condition. The guilt-modulated frontal negativity might reflect the interactions of self-reflection, condemnation, and negative emotion.

  17. Use of human papillomavirus DNA, E6/E7 mRNA, and p16 immunocytochemistry to detect and predict anal high-grade squamous intraepithelial lesions in HIV-positive and HIV-negative men who have sex with men.

    Directory of Open Access Journals (Sweden)

    Nittaya Phanuphak

    Full Text Available Men who have sex with men (MSM are at high risk of having anal cancer. Anal high-grade squamous intraepithelial lesion (HSIL is the precursor of anal cancer. We explored the use of different biomarkers associated with human papillomavirus (HPV infection and HPV-mediated cell transformation to detect and predict HSIL among HIV-positive and HIV-negative MSM.A total of 123 HIV-positive and 123 HIV-negative MSM were enrolled and followed for 12 months. High-resolution anoscopy (HRA with biopsies were performed at every visit along with anal sample collection for cytology, high-risk HPV DNA genotyping, HPV E6/E7 mRNA, and p16 immunocytochemistry. Performance characteristics and area under the receiver operator characteristics curve were calculated for these biomarkers at baseline, and Cox regression compared the usefulness of these biomarkers in predicting incident HSIL. High-risk HPV DNA, E6/E7 mRNA, and p16 immunocytochemistry each identified 43-46% of MSM whose baseline test positivity would trigger HRA referral. E6/E7 mRNA had the highest sensitivity (64.7% and correctly classified the highest number of prevalent HSIL cases. With the exception of p16 immunochemistry, most tests showed significant increases in sensitivity but decreases specificity versus anal cytology, while the overall number of correctly classified cases was not significantly different. Baseline or persistent type 16 and/or 18 HPV DNA was the only test significantly predicting incident histologic HSIL within 12 months in models adjusted for HIV status and low-grade squamous intraepithelial lesions at baseline.Countries with a high HIV prevalence among MSM and limited HRA resources may consider using biomarkers to identify individuals at high risk of HSIL. E6/E7 mRNA had the highest sensitivity for prevalent HSIL detection regardless of HIV status, whereas type 16 and/or 18 HPV DNA performed best in predicting development of incident HSIL within 12 months.

  18. Effect of negative and positive emotions on EEG spectral asymmetry.

    Science.gov (United States)

    Orgo, L; Bachmann, M; Lass, J; Hinrikus, H

    2015-08-01

    The aim of the study was to evaluate the applicability of electroencephalogram (EEG) spectral asymmetry index (SASI) for discrimination of the effect of negative and positive emotions on human brain bioelectrical activity. SASI has been previously proposed as a method to detect depression based on the balance of EEG theta and beta frequency band powers. Emotions were evoked on 22 healthy subjects using emotional pictures portraying humans from International Affective Picture System (IAPS) and late response to stimuli was examined (1700-2200 ms). Electroencephalogram (EEG) was recorded in 30 channels divided into 10 brain regions: left frontal, right frontal, left temporal, right temporal, frontal, frontocentral, central, centroparietal, parietal and occipital. Negative stimuli, compared to neutral stimuli, significantly increased SASI in frontocentral, central, centroparietal, parietal and occipital areas. Positive stimuli, compared to neutral stimuli, significantly decreased SASI in left temporal, centroparietal, parietal and occipital areas. The results indicate that SASI provides a good discrimination between the effects of negative, neutral and positive emotions on human EEG.

  19. Discrepant HPV/cytology cotesting results: Are there differences between cytology-negative versus HPV-negative cervical intraepithelial neoplasia?

    Science.gov (United States)

    Tracht, Jessica M; Davis, Antoinette D; Fasciano, Danielle N; Eltoum, Isam-Eldin A

    2017-10-01

    The objective of this study was to compare cervical high-grade squamous intraepithelial lesions subcategorized as cervical intraepithelial neoplasia-3 (CIN-3)-positive after a negative cytology result but positive for high-risk human papillomavirus (HR-HPV) testing to those with a negative HR-HPV test but positive cytology (atypical squamous cells of undetermined significance [ASCUS]-positive/HPV-negative) and to assess reasons for discrepancies. The authors retrospectively analyzed women who underwent screening with cytology and HPV testing from 2010 through 2013. After a review of surgical specimens and cytology, discrepancies were classified as sampling or interpretation error. Clinical and pathologic findings were compared. In total, 15,173 women (age range, 25-95 years; 7.1% were aged HPV and cytologic testing, and 1184 (8.4%) underwent biopsy. Cytology was positive in 19.4% of specimens, and HPV was positive in 14.5%. Eighty-four CIN-3-positive specimens were detected, including 55 that tested ASCUS-positive/HPV-positive, 11 that tested negative for intraepithelial lesion or malignancy (NILM)/HPV-positive, 10 that tested ASCUS-positive/HPV-negative, 3 that tested NILM/HPV-negative, and 5 tests that were unsatisfactory. There was no significant difference between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3 in terms of size, time to occurrence, the presence of a cytopathic effect, screening history, race, or age. Six of 11 NILM/HPV-positive cases were reclassified as ASCUS, indicating an interpreting error of 55% and a sampling error of 45%. No ASCUS-positive/HPV-negative cases were reclassified. Seven cases of CIN-3 with positive cytology were HPV-negative. There are no significant clinical or pathologic differences between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3-positive specimens. Cytologic sampling or interpretation remains the main reason for discrepancies. However, HPV-negative CIN-3 with positive cytology exists and may be

  20. A Biopsychosocial Model Based on Negative Feedback and Control

    Directory of Open Access Journals (Sweden)

    Timothy Andrew Carey

    2014-02-01

    Full Text Available Although the biopsychosocial model has been a popular topic of discussion for over four decades it has not had the traction in fields of research that might be expected of such an intuitively appealing idea. One reason for this might be the absence of an identified mechanism or a functional architecture that is authentically biopsychosocial. What is needed is a robust mechanism that is equally important to biochemical processes as it is to psychological and social processes. Negative feedback may be the mechanism that is required. Negative feedback has been implicated in the regulation of neurotransmitters as well as important psychological and social processes such as emotional regulation and the relationship between a psychotherapist and a client. Moreover, negative feedback is purported to also govern the activity of all other organisms as well as humans. Perceptual Control Theory (PCT describes the way in which negative feedback establishes control at increasing levels of perceptual complexity. Thus, PCT may be the first biopsychosocial model to be articulated in functional terms. In this paper we outline the working model of PCT and explain how PCT provides an embodied hierarchical neural architecture that utilises negative feedback to control physiological, psychological, and social variables. PCT has major implications for both research and practice and, importantly, provides a guide by which fields of research that are currently separated may be integrated to bring about substantial progress in understanding the way in which the brain alters, and is altered by, its behavioural and environmental context.

  1. A biopsychosocial model based on negative feedback and control.

    Science.gov (United States)

    Carey, Timothy A; Mansell, Warren; Tai, Sara J

    2014-01-01

    Although the biopsychosocial model has been a popular topic of discussion for over four decades it has not had the traction in fields of research that might be expected of such an intuitively appealing idea. One reason for this might be the absence of an identified mechanism or a functional architecture that is authentically biopsychosocial. What is needed is a robust mechanism that is equally important to biochemical processes as it is to psychological and social processes. Negative feedback may be the mechanism that is required. Negative feedback has been implicated in the regulation of neurotransmitters as well as important psychological and social processes such as emotional regulation and the relationship between a psychotherapist and a client. Moreover, negative feedback is purported to also govern the activity of all other organisms as well as humans. Perceptual Control Theory (PCT) describes the way in which negative feedback establishes control at increasing levels of perceptual complexity. Thus, PCT may be the first biopsychosocial model to be articulated in functional terms. In this paper we outline the working model of PCT and explain how PCT provides an embodied hierarchical neural architecture that utilizes negative feedback to control physiological, psychological, and social variables. PCT has major implications for both research and practice and, importantly, provides a guide by which fields of research that are currently separated may be integrated to bring about substantial progress in understanding the way in which the brain alters, and is altered by, its behavioral and environmental context.

  2. The fish is bad: negative food odors elicit faster and more accurate reactions than other odors

    NARCIS (Netherlands)

    Boesveldt, S.; Frasnelli, J.; Gordon, A.; Lundstrom, J.N.

    2010-01-01

    Dissociating between ‘good’ or ‘bad’ odors is arguable of crucial value for human survival, since unpleasant odors often signal danger. Therefore, negative odors demand a faster response in order to quickly avoid or move away from negative situations. We know from other sensory systems that this

  3. On multiphase negative flash for ideal solutions

    DEFF Research Database (Denmark)

    Yan, Wei; Stenby, Erling Halfdan

    2012-01-01

    There is a recent interest to solve multiphase negative flash problems where the phase amounts can be negative for normal positive feed composition. Solving such a negative flash problem using successive substitution needs an inner loop for phase distribution calculation at constant fugacity...... coefficients. It is shown that this inner loop, named here as multiphase negative flash for ideal solutions, can be solved either by Michelsen's algorithm for multiphase normal flash, or by its variation which uses F−1 phase amounts as independent variables. In either case, the resulting algorithm is actually...... simpler than the corresponding normal flash algorithm. Unlike normal flash, multiphase negative flash for ideal solutions can diverge if the feasible domain for phase amounts is not closed. This can be judged readily during the iteration process. The algorithm can also be extended to the partial negative...

  4. Negative Pressure Wound Therapy in Maxillofacial Applications

    Directory of Open Access Journals (Sweden)

    Adam J. Mellott

    2016-09-01

    Full Text Available Negative pressure wound therapy has greatly advanced the field of wound healing for nearly two decades, by providing a robust surgical adjunct technique for accelerating wound closure in acute and chronic wounds. However, the application of negative pressure wound therapy in maxillofacial applications has been relatively under utilized as a result of the physical articulations and contours of the head and neck that make it challenging to obtain an airtight seal for different negative pressure wound therapy systems. Adapting negative pressure wound therapies for maxillofacial applications could yield significant enhancement of wound closure in maxillofacial applications. The current review summarizes the basic science underlying negative pressure wound therapy, as well as specific maxillofacial procedures that could benefit from negative pressure wound therapy.

  5. Zero-truncated negative binomial - Erlang distribution

    Science.gov (United States)

    Bodhisuwan, Winai; Pudprommarat, Chookait; Bodhisuwan, Rujira; Saothayanun, Luckhana

    2017-11-01

    The zero-truncated negative binomial-Erlang distribution is introduced. It is developed from negative binomial-Erlang distribution. In this work, the probability mass function is derived and some properties are included. The parameters of the zero-truncated negative binomial-Erlang distribution are estimated by using the maximum likelihood estimation. Finally, the proposed distribution is applied to real data, the number of methamphetamine in the Bangkok, Thailand. Based on the results, it shows that the zero-truncated negative binomial-Erlang distribution provided a better fit than the zero-truncated Poisson, zero-truncated negative binomial, zero-truncated generalized negative-binomial and zero-truncated Poisson-Lindley distributions for this data.

  6. Adolescents’ Negative Experiences in Organized Youth Activities

    Directory of Open Access Journals (Sweden)

    Jodi Dworkin

    2007-03-01

    Full Text Available Research indicates that organized youth activities are most often a context of positive development. However, there is a smaller body of evidence suggesting that these activities are sometimes a context of negative experiences that may impede learning or lead to dropping out. To better understand negative experiences in youth activities, we conducted ten focus groups with adolescents. Youths’ descriptions provide an overview of the range of types of negative experiences they encountered, as well as how they responded to them. The most frequent types of negative experiences involved peers and peer group dynamics and aversive behavior attributed to the adult leaders of the activities. The youth described two types of responses to their negative experiences - a passive response of feeling negative emotions, and active coping, which sometimes led to learning.

  7. Caracterização fenotípica da resistência a antimicrobianos e detecção do gene mecA em Staphylococcus spp. coagulase-negativos isolados de amostras animais e humanas Phenotypic characterization of antimicrobial resistance and detection of the mecA gene in coagulase-negative Staphylococcus spp. isolates from animal and human samples

    Directory of Open Access Journals (Sweden)

    Lidiane de Castro Soares

    2008-08-01

    Full Text Available Os estafilococos coagulase-negativos (ECN fazem parte da microbiota normal da pele e, apesar de terem sido considerados saprófitas por muito tempo, o seu significado clínico como agente etiológico tem aumentado com o passar dos anos. Neste estudo, foram obtidos 72 isolados de ECN a partir de amostras do conduto auditivo de cães, de mastite bovina e de infecções humanas. Staphylococcus xylosus foi o microrganismo mais isolado, nas amostras animais, e S. cohnii subsp. cohnii em humanos. Os isolados foram avaliados de modo a traçar o perfil fenotípico de sua resistência aos antimicrobianos mais indicados no tratamento de infecções estafilocócicas. Foi detectado um elevado nível de resistência à penicilina e ampicilina. A gentamicina, a vancomicina e a associação ampicilina+sulbactam foram eficientes frente aos isolados testados. A resistência à oxacilina foi avaliada por meio dos testes de difusão em disco modificada, ágar screen, microdiluição em caldo e diluição em ágar para constatar, se à semelhança do que ocorre com os estafilococos coagulase-positivo, esta pode ser mediada pelo gene mecA e apresentada de forma heterogênea. A presença do gene mecA foi determinada pelo método da Reação em Cadeia de Polimerase (PCR, sendo 5,6% dos isolados mecA positivos.Coagulase-negative staphylococci (SCN make part of the normal microbiota skin and although they have been considered saprophytics for years, nowadays their clinical significance as an etiologic agent has increased. In this study, 72 SCN isolates obtained from external ear canals of dogs, bovine mastitis and human nosocomial infections were evaluated. Staphylococcus xylosus was the most prevalent microorganism in animal samples and S. cohnii subsp. cohnii in human samples. SCN isolates were evaluated in order to establish a phenotypical resistance pattern towards the most indicated antibiotics for staphyloccocal infections. A high level of resistance to penicillin

  8. Analyzing negative ties in social networks

    Directory of Open Access Journals (Sweden)

    Mankirat Kaur

    2016-03-01

    Full Text Available Online social networks are a source of sharing information and maintaining personal contacts with other people through social interactions and thus forming virtual communities online. Social networks are crowded with positive and negative relations. Positive relations are formed by support, endorsement and friendship and thus, create a network of well-connected users whereas negative relations are a result of opposition, distrust and avoidance creating disconnected networks. Due to increase in illegal activities such as masquerading, conspiring and creating fake profiles on online social networks, exploring and analyzing these negative activities becomes the need of hour. Usually negative ties are treated in same way as positive ties in many theories such as balance theory and blockmodeling analysis. But the standard concepts of social network analysis do not yield same results in respect of each tie. This paper presents a survey on analyzing negative ties in social networks through various types of network analysis techniques that are used for examining ties such as status, centrality and power measures. Due to the difference in characteristics of flow in positive and negative tie networks some of these measures are not applicable on negative ties. This paper also discusses new methods that have been developed specifically for analyzing negative ties such as negative degree, and h∗ measure along with the measures based on mixture of positive and negative ties. The different types of social network analysis approaches have been reviewed and compared to determine the best approach that can appropriately identify the negative ties in online networks. It has been analyzed that only few measures such as Degree and PN centrality are applicable for identifying outsiders in network. For applicability in online networks, the performance of PN measure needs to be verified and further, new measures should be developed based upon negative clique concept.

  9. On the Consumption of Negative Feelings

    OpenAIRE

    Andrade, Eduardo B.; Cohen, Joel B

    2007-01-01

    How can the hedonistic assumption (i.e., people's willingness to pursue pleasure and avoid pain) be reconciled with people choosing to expose themselves to experiences known to elicit negative feelings? We assess how (1) the intensity of the negative feelings, (2) positive feelings in the aftermath, and (3) the coactivation of positive and negative feelings contribute to our understanding of such behavior. In a series of 4 studies, consumers with either approach or avoidance tendencies (towar...

  10. Art, Terrorism and the Negative Sublime

    Directory of Open Access Journals (Sweden)

    Arnold Berleant

    2009-01-01

    Full Text Available The range of the aesthetic has expanded to cover not only a wider range of objects and situations of daily life but also to encompass the negative. This includes terrorism, whose aesthetic impact is central to its use as a political tactic. The complex of positive and negative aesthetic values in terrorism are explored, introducing the concept of the sublime as a negative category to illuminate the analysis and the distinctive aesthetic of terrorism.

  11. Exploring Impact: Negative Effects of Social Networks

    OpenAIRE

    Egbert, Henrik; Sedlarski, Teodor

    2011-01-01

    he sociological literature on social networks emphasizes by and large positive network effects. Negative effects of such networks are discussed rather rarely. This paper tackles negative effects by applying economic theory, particularly neoclassical theory, new institutional theory and the results from experimental economics to the concept of social networks. In the paper it is assumed that social networks are exclusive and since exclusiveness affects the allocation of resources, negative ext...

  12. PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients

    Directory of Open Access Journals (Sweden)

    Hiroji Iwata

    2017-08-01

    Full Text Available Purpose: To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy–resistant metastatic breast cancer. Patients and Methods: The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3 trial, a double-blind phase III study, included 521 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs were assessed on study treatment and at the end of treatment. Results: This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71 or placebo plus fulvestrant (n = 31. Palbociclib plus fulvestrant improved progression-free survival (PFS compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065. The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92% and leukopenia (29%; febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. Conclusion: This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.

  13. PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy-Safety and Efficacy in Asian Patients.

    Science.gov (United States)

    Iwata, Hiroji; Im, Seock-Ah; Masuda, Norikazu; Im, Young-Hyuck; Inoue, Kenichi; Rai, Yoshiaki; Nakamura, Rikiya; Kim, Jee Hyun; Hoffman, Justin T; Zhang, Ke; Giorgetti, Carla; Iyer, Shrividya; Schnell, Patrick T; Bartlett, Cynthia Huang; Ro, Jungsil

    2017-08-01

    To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy-resistant metastatic breast cancer. The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3) trial, a double-blind phase III study, included 521 patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs) were assessed on study treatment and at the end of treatment. This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71) or placebo plus fulvestrant (n = 31). Palbociclib plus fulvestrant improved progression-free survival (PFS) compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached) but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065). The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92%) and leukopenia (29%); febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.

  14. Negation of resultative and progressive periphrases

    Directory of Open Access Journals (Sweden)

    Raquel González Rodríguez

    2015-05-01

    Full Text Available This paper focuses on resultative and progressive periphrases in Spanish: and , respectively. These periphrases have been associated with several negated constructions. On the one hand, the negative particle no ‘not’ can precede the auxiliary verb ( and ; on the other hand, we have the structure . Contrary to what has been suggested in the literature, I will show that these negative constructions have a different interpretation and develop a semantic analysis of them. Furthermore, I will offer new evidence in favor of the existence of negative events.

  15. Human ehrlichiosis

    Directory of Open Access Journals (Sweden)

    Đokić Milomir

    2006-01-01

    Full Text Available Background. Human ehrlichiosis is a newly recognized disease. It is a tick-borne disease caused by several bacterial species of the genhus Erlichia. These are small gram-negative pleomorphic cocci, that are obligatory intracellular bacteria. Tick Ixodes is the principle vector in Europe, and Amblyomma americanum in the United States. Bacterial organisms replicate in a tick, and are transmited from infected cells in a vector to the blood cells of animals or humans. Human ehrlichiosis is a name for a group of diseases caused by different species of Ehrlichia. One of them is the disease named human monocytic ehrlichiosis, caused by Ehrlichia chaffeensis, and the other is a human granulocytic ehrlichiosis caused by Anaplasma phagocytophilia. Case report. We reported a 23-year-old patient admitted for the clinical treatment with the symptoms of high febrility (above 40 °C, headache, vomiting, general weakness and exhaustion, but without data on a tick bite. The patient was treated with trimetoprim-sulfamethoxazole for a week when Ehrlichia chaffeensis was confirmed by the immunofluoroscence test, and the therapy contimed with doxacyclin. Conclusion. Human ehrlichiosis is also present in our country, so this disease should be considered everyday, especially in infectology practice.

  16. Scope of negation detection in sentiment analysis

    NARCIS (Netherlands)

    Dadvar, M.; Hauff, C.; de Jong, Franciska M.G.

    2011-01-01

    An important part of information-gathering behaviour has always been to find out what other people think and whether they have favourable (positive) or unfavourable (negative) opinions about the subject. This survey studies the role of negation in an opinion-oriented information-seeking system. We

  17. Appendicitis: A Study of Negative Appendicectomies | Kpolugbo ...

    African Journals Online (AJOL)

    52.8% were confirmed on histology. The diagnostic error (negative appendicectomy) was 47.2%. the error was lower in males (35%) compared with females. The reason for the high negative appendicectomy in women is pelvic inflammatory diseases, which mimics acute appendicitis. Post-operative complications were ...

  18. Negating the Infinitive in Biblical Hebrew

    DEFF Research Database (Denmark)

    Ehrensvärd, Martin Gustaf

    1999-01-01

    The article examines the negating of the infinitive in biblical and post-biblical Hebrew. The combination of the negation ayin with infinitive is widely claimed to belong to the linguistic layer commonly referred to as late biblical Hebrew and scholars use it to late-date texts. The article showa...

  19. Repetitive negative thinking as a transdiagnostic process

    NARCIS (Netherlands)

    Ehring, T.; Watkins, E.R.

    2008-01-01

    The current paper provides an updated review of repetitive negative thinking as a transdiagnostic process. It is shown that elevated levels of repetitive negative thinking are present across a large range of Axis I disorders and appear to be causally involved in the maintenance of emotional

  20. Aspects of Negation in Classical Greek.

    Science.gov (United States)

    Taylor, Daniel J.

    1972-01-01

    Traditional grammars are criticized as having obscured or omitted many significant features of negation patterns in classical Greek. The author demonstrates that negation in Greek extensively involves semantic and syntactic factors. Certain of the factors are thoroughly embedded in the traditional approach to grammar, while others are derived from…

  1. Visual content of words delays negation.

    Science.gov (United States)

    Orenes, Isabel; Santamaría, Carlos

    2014-11-01

    Many studies have shown the advantage of processing visualizable words over non-visualizables due to the associated image code. The present paper reports the case of negation in which imagery could slow down processing. Negation reverses the truth value of a proposition from false to true or vice versa. Consequently, negation works only on propositions (reversing their truth value) and cannot apply directly to other forms of knowledge representation such as images (although they can be veridical or not). This leads to a paradoxical hypothesis: despite the advantage of visualizable words for general processing, the negation of clauses containing words related to the representation of an image would be more difficult than negation containing non-visualizable words. Two experiments support this hypothesis by showing that sentences with a previously negated visualizable word took longer to be read than sentences with previously negated non-visualizable words. The results suggest that a verbal code is used to process negation. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Negative Priming in Free Recall Reconsidered

    Science.gov (United States)

    Hanczakowski, Maciej; Beaman, C. Philip; Jones, Dylan M.

    2016-01-01

    Negative priming in free recall is the finding of impaired memory performance when previously ignored auditory distracters become targets of encoding and retrieval. This negative priming has been attributed to an aftereffect of deploying inhibitory mechanisms that serve to suppress auditory distraction and minimize interference with learning and…

  3. Negative appendicectomy: evaluation of ultrasonography and ...

    African Journals Online (AJOL)

    Background: High negative appendicectomy rates are no longer acceptable with improvements in imaging techniques and clinical prediction rules. The use of ultrasound and CT scan in addition to clinical assessment and blood investigations has greatly reduced the negative appendicectomy rate to less than 10%.

  4. Criticism and the Ethics of Negative Reviews

    Science.gov (United States)

    Peters, Michael A.

    2014-01-01

    This paper is an attempt to work through my own angst at a negative review of my "Education, Philosophy and Politics," reviewed recently by Ian Stronach for the "British Educational Research Journal," and to provide a therapeutic reading of the ethics of negative reviews. What of "shots in the dark" and should there…

  5. A Negative Permeability Material at Red Light

    DEFF Research Database (Denmark)

    Yuan, Hsiao-Kuan; Chettiar, Uday K.; Cai, Wenshan

    2007-01-01

    A negative permeability in a periodic array of pairs of thin silver strips is demonstrated experimentally for two distinct samples. The effect of the strip surface roughness on negative permeability is evaluated. The first sample, Sample A, is fabricated of thinner strips with a root mean square ...

  6. Negative creep in nickel base superalloys

    DEFF Research Database (Denmark)

    Dahl, Kristian Vinter; Hald, John

    2004-01-01

    Negative creep describes the time dependent contraction of a material as opposed to the elongation seen for a material experiencing normal creep behavior. Negative creep occurs because of solid state transformations that results in lattice contractions. For most applications negative creep...... will have no practical implications but under certain conditions it may become critical. For bolts and fasteners, which are highly constrained during service, negative creep may lead to dramatically increased stresses and eventually to failure. The article was inspired by a recent failure of Nimonic 80A...... bolts in German gas turbines. As a result of this failure similar bolts from Danish gas turbines of the same type were investigated and it was found that the bolts had experienced negative creep during service....

  7. Small membranes under negative surface tension.

    Science.gov (United States)

    Avital, Yotam Y; Farago, Oded

    2015-03-28

    We use computer simulations and a simple free energy model to study the response of a bilayer membrane to the application of a negative (compressive) mechanical tension. Such a tension destabilizes the long wavelength undulation modes of giant vesicles, but it can be sustained when small membranes and vesicles are considered. Our negative tension simulation results reveal two regimes-(i) a weak negative tension regime characterized by stretching-dominated elasticity and (ii) a strong negative tension regime featuring bending-dominated elastic behavior. This resembles the findings of the classic Evans and Rawicz micropipette aspiration experiment in giant unilamellar vesicles (GUVs) [E. Evans and W. Rawicz, Phys, Rev. Lett. 64, 2094 (1990)]. However, in GUVs the crossover between the two elasticity regimes occurs at a small positive surface tension, while in smaller membranes it takes place at a moderate negative tension. Another interesting observation concerning the response of a small membrane to negative surface tension is related to the relationship between the mechanical and fluctuation tensions, which are equal to each other for non-negative values. When the tension decreases to negative values, the fluctuation tension γ drops somewhat faster than the mechanical tension τ in the small negative tension regime, before it saturates (and becomes larger than τ) for large negative tensions. The bending modulus exhibits an "opposite" trend. It remains almost unchanged in the stretching-dominated elastic regime, and decreases in the bending-dominated regime. Both the amplitudes of the thermal height undulations and the projected area variations diverge at the onset of mechanical instability.

  8. TLR4 as a negative regulator of keratinocyte proliferation.

    Directory of Open Access Journals (Sweden)

    Guergana Iotzova-Weiss

    Full Text Available TLR4 is an innate immune receptor with expression in human skin, keratinocytes as well as squamous cell carcinoma (SCC of the skin. In the present study we investigate the role of TLR4 as a negative regulator of keratinocyte proliferation. We present here that the expression of TLR4 increased with the differentiation of cultured keratinocytes in a passage-dependent manner or under calcium-rich conditions. Moreover, the down-regulation of TLR4 by specific knockdown increased the proliferation of HaCaT keratinocytes in vitro. In addition, subcutaneously injected HaCaT keratinocytes with shTLR4 formed growing tumors in nude mice. In contrast, we observed lower proliferation and increased migration in vitro of the SCC13 cell line stably overexpressing TLR4 in comparison to SCC13 TLR4 negative cells. In vivo, SCC13 TLR4-overexpressing tumors showed delayed growth in comparison to TLR4 negative tumors. The overexpression of TLR4 in SCC13 tumor cells was followed by phosphorylation of ERK1/2 and JNK and increased expression of ATF3. In gene expression arrays, the overexpression of TLR4 in tumor cells correlated with gene expression of ATF-3, IL-6, CDH13, CXCL-1 and TFPI. In summary, TLR4 negatively regulates the proliferation of keratinocytes and its overexpression reduces tumor growth of SCC cells.

  9. TLR4 as a negative regulator of keratinocyte proliferation.

    Science.gov (United States)

    Iotzova-Weiss, Guergana; Freiberger, Sandra N; Johansen, Pål; Kamarachev, Jivko; Guenova, Emmanuella; Dziunycz, Piotr J; Roux, Guillaume A; Neu, Johannes; Hofbauer, Günther F L

    2017-01-01

    TLR4 is an innate immune receptor with expression in human skin, keratinocytes as well as squamous cell carcinoma (SCC) of the skin. In the present study we investigate the role of TLR4 as a negative regulator of keratinocyte proliferation. We present here that the expression of TLR4 increased with the differentiation of cultured keratinocytes in a passage-dependent manner or under calcium-rich conditions. Moreover, the down-regulation of TLR4 by specific knockdown increased the proliferation of HaCaT keratinocytes in vitro. In addition, subcutaneously injected HaCaT keratinocytes with shTLR4 formed growing tumors in nude mice. In contrast, we observed lower proliferation and increased migration in vitro of the SCC13 cell line stably overexpressing TLR4 in comparison to SCC13 TLR4 negative cells. In vivo, SCC13 TLR4-overexpressing tumors showed delayed growth in comparison to TLR4 negative tumors. The overexpression of TLR4 in SCC13 tumor cells was followed by phosphorylation of ERK1/2 and JNK and increased expression of ATF3. In gene expression arrays, the overexpression of TLR4 in tumor cells correlated with gene expression of ATF-3, IL-6, CDH13, CXCL-1 and TFPI. In summary, TLR4 negatively regulates the proliferation of keratinocytes and its overexpression reduces tumor growth of SCC cells.

  10. Negated bio-events: analysis and identification

    Science.gov (United States)

    2013-01-01

    Background Negation occurs frequently in scientific literature, especially in biomedical literature. It has previously been reported that around 13% of sentences found in biomedical research articles contain negation. Historically, the main motivation for identifying negated events has been to ensure their exclusion from lists of extracted interactions. However, recently, there has been a growing interest in negative results, which has resulted in negation detection being identified as a key challenge in biomedical relation extraction. In this article, we focus on the problem of identifying negated bio-events, given gold standard event annotations. Results We have conducted a detailed analysis of three open access bio-event corpora containing negation information (i.e., GENIA Event, BioInfer and BioNLP’09 ST), and have identified the main types of negated bio-events. We have analysed the key aspects of a machine learning solution to the problem of detecting negated events, including selection of negation cues, feature engineering and the choice of learning algorithm. Combining the best solutions for each aspect of the problem, we propose a novel framework for the identification of negated bio-events. We have evaluated our system on each of the three open access corpora mentioned above. The performance of the system significantly surpasses the best results previously reported on the BioNLP’09 ST corpus, and achieves even better results on the GENIA Event and BioInfer corpora, both of which contain more varied and complex events. Conclusions Recently, in the field of biomedical text mining, the development and enhancement of event-based systems has received significant interest. The ability to identify negated events is a key performance element for these systems. We have conducted the first detailed study on the analysis and identification of negated bio-events. Our proposed framework can be integrated with state-of-the-art event extraction systems. The

  11. Information Filtering Based on Users' Negative Opinions

    Science.gov (United States)

    Guo, Qiang; Li, Yang; Liu, Jian-Guo

    2013-05-01

    The process of heat conduction (HC) has recently found application in the information filtering [Zhang et al., Phys. Rev. Lett.99, 154301 (2007)], which is of high diversity but low accuracy. The classical HC model predicts users' potential interested objects based on their interesting objects regardless to the negative opinions. In terms of the users' rating scores, we present an improved user-based HC (UHC) information model by taking into account users' positive and negative opinions. Firstly, the objects rated by users are divided into positive and negative categories, then the predicted interesting and dislike object lists are generated by the UHC model. Finally, the recommendation lists are constructed by filtering out the dislike objects from the interesting lists. By implementing the new model based on nine similarity measures, the experimental results for MovieLens and Netflix datasets show that the new model considering negative opinions could greatly enhance the accuracy, measured by the average ranking score, from 0.049 to 0.036 for Netflix and from 0.1025 to 0.0570 for Movielens dataset, reduced by 26.53% and 44.39%, respectively. Since users prefer to give positive ratings rather than negative ones, the negative opinions contain much more information than the positive ones, the negative opinions, therefore, are very important for understanding users' online collective behaviors and improving the performance of HC model.

  12. Context processing and negative symptoms in schizophrenia.

    Science.gov (United States)

    Thoma, Patrizia; Zoppelt, Diana; Wiebel, Burkhard; Daum, Irene

    2007-05-01

    The objective of the study was to test the assumption that patients with a high level of negative symptoms show disproportionate impairments of inhibition and multitasking, both representing an underlying context processing mechanism. A total of 26 schizophrenia patients scoring high or low on negative symptoms (Positive and Negative Syndrome Scale) and a group of 13 healthy controls were assessed on measures of response inhibition (AX- Continuous Performance Task, Stroop Test) and multitasking (Dual Task, Trail Making Test). Only the high negative symptoms group showed significantly higher inhibition costs and multitasking costs than healthy controls. In the AX-Continuous Performance Test, inhibition costs exceeded context costs in patients with more severe negative symptoms, while in controls a tendency towards the reverse pattern emerged. There were no statistically significant effects involving the patient group with lower negative symptom scores. The pattern of results suggests that primarily patients with more severe negative symptoms have difficulties benefiting from contextual information. The deficit may manifest itself via increased multitasking costs and increased inhibition costs but also via reduced context costs.

  13. Negative HPV screening test predicts low cervical cancer risk better than negative Pap test

    Science.gov (United States)

    Based on a study that included more than 1 million women, investigators at NCI have determined that a negative test for HPV infection compared to a negative Pap test provides greater safety, or assurance, against future risk of cervical cancer.

  14. Negative staining and cryo-negative staining of macromolecules and viruses for TEM.

    Science.gov (United States)

    De Carlo, Sacha; Harris, J Robin

    2011-02-01

    In this review we cover the technical background to negative staining of biomolecules and viruses, and then expand upon the different possibilities and limitations. Topics range from conventional air-dry negative staining of samples adsorbed to carbon support films, the variant termed the "negative staining-carbon film" technique and negative staining of samples spread across the holes of holey-carbon support films, to a consideration of dynamic/time-dependent negative staining. For each of these approaches examples of attainable data are given. The cryo-negative staining technique for the specimen preparation of frozen-hydrated/vitrified samples is also presented. A detailed protocol to successfully achieve cryo-negative staining with ammonium molybdate is given, as well as examples of data, which support the claim that cryo-negative staining provides a useful approach for the high-resolution study of macromolecular and viral structure. Copyright © 2009 Elsevier Ltd. All rights reserved.

  15. Antimitochondrial antibody-negative primary biliary cirrhosis.

    Science.gov (United States)

    Mendes, Flavia; Lindor, Keith D

    2008-06-01

    There is a subset of patients who have biochemical and histologic features consistent with primary biliary cirrhosis (PBC) who lack antimitochondrial antibodies (AMA). This entity is usually referred to as AMA-negative PBC or alternatively autoimmune cholangitis. Patients who have AMA-negative PBC are believed to have a similar clinical course, response to treatment, and prognosis as their AMA-positive counterparts. As more sensitive and specific serologic tests are developed to detect serum AMA, it is possible we may find that these patients initially believed to be AMA-negative are indeed AMA-positive, suggesting a single disease process.

  16. Does Negative Type Characterize the Round Sphere?

    DEFF Research Database (Denmark)

    Kokkendorff, Simon Lyngby

    2007-01-01

    We discuss the measure theoretic metric invariants extent, mean distance and symmetry ratio and their relation to the concept of negative type of a metric space. A conjecture stating that a compact Riemannian manifold with symmetry ratio 1 must be a round sphere, was put forward in a previous paper....... We resolve this conjecture in the class of Riemannian symmetric spaces by showing, that a Riemannian manifold with symmetry ratio 1 must be of negative type and that the only compact Riemannian symmetric spaces of negative type are the round spheres....

  17. Finite Metric Spaces of Strictly negative Type

    DEFF Research Database (Denmark)

    Hjorth, Poul G.

    If a finite metric space is of strictly negative type then its transfinite diameter is uniquely realized by an infinite extent (“load vector''). Finite metric spaces that have this property include all trees, and all finite subspaces of Euclidean and Hyperbolic spaces. We prove that if the distance...... matrix of a finite metric space is both hypermetric and regular, then it is of strictly negative type. We show that the strictly negative type finite subspaces of spheres are precisely those which do not contain two pairs of antipodal points....

  18. Triple-Negative Breast Cancer: Adjuvant Therapeutic Options

    Directory of Open Access Journals (Sweden)

    Ayca Gucalp

    2011-01-01

    Full Text Available Triple-negative breast cancer (TNBC, a subtype distinguished by negative immunohistochemical assays for expression of the estrogen and progesterone receptors (ER/PR and human epidermal growth factor receptor-2(HER2 represents 15% of all breast cancers. Patients with TNBC generally experience a more aggressive clinical course with increased risk of disease progression and poorer overall survival. Furthermore, this subtype accounts for a disproportionate number of disease-related mortality in part due to its aggressive natural history and our lack of effective targeted agents beyond conventional cytotoxic chemotherapy. In this paper, we will review the epidemiology, risk factors, prognosis, and the molecular and clinicopathologic features that distinguish TNBC from other subtypes of breast cancer. In addition, we will examine the available data for the use of cytotoxic chemotherapy in the treatment of TNBC in both the neoadjuvant and adjuvant setting and explore the ongoing development of newer targeted agents.

  19. V-antigen homologs in pathogenic gram-negative bacteria.

    Science.gov (United States)

    Sawa, Teiji; Katoh, Hideya; Yasumoto, Hiroaki

    2014-05-01

    Gram-negative bacteria cause many types of infections in animals from fish and shrimps to humans. Bacteria use Type III secretion systems (TTSSs) to translocate their toxins directly into eukaryotic cells. The V-antigen is a multifunctional protein required for the TTSS in Yersinia and Pseudomonas aeruginosa. V-antigen vaccines and anti-V-antigen antisera confer protection against Yersinia or P. aeruginosa infections in animal models. The V-antigen forms a pentameric cap structure at the tip of the Type III secretory needle; this structure, which has evolved from the bacterial flagellar cap structure, is indispensable for toxin translocation. Various pathogenic gram-negative bacteria such as Photorhabdus luminescens, Vibrio spp., and Aeromonas spp. encode homologs of the V-antigen. Because the V-antigens of pathogenic gram-negative bacteria play a key role in toxin translocation, they are potential therapeutic targets for combatting bacterial virulence. In the USA and Europe, these vaccines and specific antibodies against V-antigens are in clinical trials investigating the treatment of Yersinia or P. aeruginosa infections. Pathogenic gram-negative bacteria are of great interest because of their ability to infect fish and shrimp farms, their potential for exploitation in biological terrorism attacks, and their ability to cause opportunistic infections in humans. Thus, elucidation of the roles of the V-antigen in the TTSS and mechanisms by which these functions can be blocked is critical to facilitating the development of improved anti-V-antigen strategies. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

  20. Perceived Social Competence, Negative Social Interactions, and Negative Cognitive Style Predict Depressive Symptoms during Adolescence

    Science.gov (United States)

    Lee, Adabel; Hankin, Benjamin L.; Mermelstein, Robin J.

    2010-01-01

    The current study examined whether negative interactions with parents and peers would mediate the longitudinal association between perceived social competence and depressive symptoms and whether a negative cognitive style would moderate the longitudinal association between negative interactions with parents and increases in depressive symptoms.…

  1. The Aesthetic Value Embedded in the Negative Number History and the Negative Number Instruction

    Directory of Open Access Journals (Sweden)

    Shu-Chuan Chen

    2013-12-01

    Full Text Available The purpose of this article is to interpret the meaning and the aesthetics value in the history of negative numbers and the instruction of negative numbers. The argument begins with explaining the reasons why the aesthetic approach can be recommended to inspire the instruction of negative numbers. The aesthetic contents of negative numbers are then analyzed and presented. The author further explicates the beauty embedded in negative numbers can be demonstrated through their developmental history. This article ends up with emphasizing the 4 merits of aesthetic viewpoints in broadening the visions of the negative number instruction; they are as follows: (1 to calm the restlessness of negative number learning; (2 to inspire student to pay more attention to number learning; (3 to better the understanding of negative number algorithm through the aesthetic intuition afforded by two examples of figure images showing that "subtracting a negative number by adding its opposite" and that "the multiplication of two negative numbers being positive"; (4 to assist student in facing and overcoming the problems in learning negative numbers. The teachers are encouraged to facilitate students to embrace the aesthetic value of negative numbers and to tackle students’ problems in advanced mathematics learning by taking into consideration of their cognitive abilities and mathematic performance.

  2. The chameleonic nature of French ni : negative coordination in a negative concord language

    NARCIS (Netherlands)

    Doetjes, Jenny

    2005-01-01

    The main goal of this paper is to defend the claim that ni, the French counterpart of neither and nor is always a negative conjunction which takes part in the negative concord system of French. The interpretation one seems to get for this negative concord ni varies depending on the environment where

  3. Production of negatively charged radioactive ion beams

    Science.gov (United States)

    Liu, Y.; Stracener, D. W.; Stora, T.

    2017-08-01

    Beams of short-lived radioactive nuclei are needed for frontier experimental research in nuclear structure, reactions, and astrophysics. Negatively charged radioactive ion beams have unique advantages and allow for the use of a tandem accelerator for post-acceleration, which can provide the highest beam quality and continuously variable energies. Negative ion beams can be obtained with high intensity and some unique beam purification techniques based on differences in electronegativity and chemical reactivity can be used to provide beams with high purity. This article describes the production of negative radioactive ion beams at the former holifield radioactive ion beam facility at Oak Ridge National Laboratory and at the CERN ISOLDE facility with emphasis on the development of the negative ion sources employed at these two facilities. ).

  4. Origin of Negative Longitudinal Piezoelectric Effect.

    Science.gov (United States)

    Liu, Shi; Cohen, R E

    2017-11-17

    Piezoelectrics with negative longitudinal piezoelectric coefficients will contract in the direction of an applied electric field. Such piezoelectrics are thought to be rare, but there is no fundamental physics preventing the realization of negative longitudinal piezoelectric effect in a single-phase material. Using first-principles calculations, we demonstrate that several hexagonal ABC ferroelectrics possess significant negative longitudinal piezoelectric effects. The data mining of a first-principles-based database of piezoelectrics reveals that this effect is a general phenomenon. The origin of this unusual piezoelectric response relies on the strong ionic bonds associated with small effective charges and rigid potential energy surfaces. Moreover, ferroelectrics with negative longitudinal piezoelectric coefficients show anomalous pressure-enhanced ferroelectricity. Our results offer design principles to aid the search for new piezoelectrics for novel electromechanical device applications.

  5. Finite Metric Spaces of Strictly Negative Type

    DEFF Research Database (Denmark)

    Hjorth, Poul; Lisonek, P.; Markvorsen, Steen

    1998-01-01

    We prove that, if a finite metric space is of strictly negative type, then its transfinite diameter is uniquely realized by the infinite extender (load vector). Finite metric spaces that have this property include all spaces on two, three, or four points, all trees, and all finite subspaces...... of Euclidean spaces. We prove that, if the distance matrix is both hypermetric and regular, then it is of strictly negative type. We show that the strictly negative type finite subspaces of spheres are precisely those which do not contain two pairs of antipodal points. In connection with an open problem raised...... by Kelly, we conjecture that all finite subspaces of hyperbolic spaces are hypermetric and regular, and hence of strictly negative type. (C) 1998 Elsevier Science Inc....

  6. How to target estrogen receptor-negative breast cancer?

    Science.gov (United States)

    Rochefort, H; Glondu, M; Sahla, M E; Platet, N; Garcia, M

    2003-06-01

    Estrogen receptor (ER)-positive breast cancers generally have a better prognosis and are often responsive to anti-estrogen therapy, which is the first example of a successful therapy targeted on a specific protein, the ER. Unfortunately ER-negative breast cancers are more aggressive and unresponsive to anti-estrogens. Other targeted therapies are thus urgently needed, based on breast cancer oncogene inhibition or suppressor gene activation as far as molecular studies have demonstrated the alteration of expression, or structure of these genes in human breast cancer. Using the MDA-MB.231 human breast cancer cell line as a model of ER-negative breast cancers, we are investigating two of these approaches in our laboratory. Our first approach was to transfect the ER or various ER-deleted variants into an ER-negative cell line in an attempt to recover anti-estrogen responsiveness. The unliganded receptor, and surprisingly estradiol, were both found to inhibit tumor growth and invasiveness in vitro and in vivo. The mechanisms of these inhibitions in ER-negative cancer cells are being studied, in an attempt to target the ER sequence responsible for such inhibition in these cancer cells. Another strategy is trying to inhibit the activity or expression of an oncogene specifically overexpressed in most breast cancers. This approach was recently shown by others to be efficient in breast cancer therapy with HER2-Neu oncogene amplification using Herceptin. Without excluding other molecular putative targets, we have focused our research on cathepsin D as a potential target, since it is often overexpressed in aggressive human breast cancers, including ER-negative tumors, and rarely associated with HER2-Neu amplification. Our first results obtained in vitro on cell lines and in vivo in tumor xenografts in nude mice, illustrate that the mode of action of cathepsin D in breast cancer is useful to guide the development of these therapies. In the past 20 years we have learned that the

  7. Topical negative pressure stimulates endothelial migration and proliferation: a suggested mechanism for improved integration of Integra.

    Science.gov (United States)

    Baldwin, Christopher; Potter, Matthew; Clayton, Elizabeth; Irvine, Laurie; Dye, Julian

    2009-01-01

    Topical negative pressure is an effective technique to promote wound healing and the integration of skin graft and synthetic dermal equivalents. We describe an in vitro model to investigate the effect of negative pressure on angiogenesis, a pivotal step. Dermal fibroblasts or human microvascular endothelial cells were cultured on Integra and subjected to intermittent or continuous negative pressure. At fixed intervals of over 120 hours, the Integra was fixed and assessed for cell migration (microscopy), cell viability (MTS assay), and cell proliferation (Ki67 immunostaining). Under control conditions, endothelial cells formed a monolayer and failed to ingress, whereas fibroblasts migrated throughout the Integra within 24 hours. Negative pressure switches endothelial cell to a migratory and proliferative phenotype. Ingress is greatest with intermittent rather than continuous negative pressure. It has no effect on dermal fibroblast function. This study identifies an important, potential pro-angiogenic mechanism by which topical negative pressure promotes wound healing.

  8. Negative pressure pulmonary oedema after septoplasty.

    Science.gov (United States)

    García de Hombre, Alina M; Cuffini, Alejandro; Bonadeo, Alejandro

    2013-01-01

    Negative pressure pulmonary oedema (NPPO) is an anaesthetic complication due to acute obstruction of the upper airway, whose main cause is laryngospasm. The pathophysiology involves a strong negative intrapleural pressure during inspiration against a closed glottis, which triggers excessive pressure in the pulmonary microvasculature. Although its diagnosis can be difficult, its recognition helps to minimise morbidity and mortality. This article presents a case of NPPO due to postextubation laryngospasm. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  9. Optical Negative Refraction in Ferrofluids with Magnetocontrollability

    Science.gov (United States)

    2010-01-22

    Optical Negative Refraction in Ferrofluids with Magnetocontrollability Y. Gao,1,2 J. P. Huang,1,* Y.M. Liu,3 L. Gao,4 K.W. Yu,2 and X. Zhang3...China (Received 5 October 2009; published 20 January 2010) We numerically demonstrate optical negative refraction in ferrofluids containing isotropic...certain soft materials. As a result, we reveal, for the first time, a new class of all-angle broadband optical nega- tive refraction in ferrofluids with

  10. Negative thermal expansion in framework compounds

    Indian Academy of Sciences (India)

    2015-11-27

    Nov 27, 2015 ... We have studied negative thermal expansion (NTE) compounds with chemi- cal compositions of NX2O8 and NX2O7 (N=Zr, Hf and X=W, Mo, V) and M2O (M=Cu, Ag) using the techniques of inelastic neutron scattering and lattice dynamics. There is a large variation in the negative thermal expansion ...

  11. What makes dreams positive or negative: relations to fundamental dimensions of positive and negative mood.

    Science.gov (United States)

    Kallmeyer, R J; Chang, E C

    1998-02-01

    The present study examined the general emotional content of dreams reported by individuals who typically experience "positive" versus "negative" dreams. Self-reports of the 153 participants indicated that positive versus negative dreamers (ns = 42 and 24, respectively) generally experienced more positive emotions, e.g., joviality, self-assurance, and fewer negative emotions, e.g., fear, sadness. No differences were found in the self-reports of the participants in the experience of surprise, guilt, fatigue, and shyness between the groups, hence, positive and negative dreams do not appear to reflect simply more positive and fewer negative emotions, respectively.

  12. Negation without symbols: the importance of recurrence and context in linguistic negation.

    Science.gov (United States)

    Huette, Stephanie; Anderson, Sarah

    2012-09-01

    A simple recurrent network with a perceptual simulation layer was trained on a corpus of affirmative and negated sentences. Linguistic negation can be encoded by the network via the inclusion (or absence) of features and categories associated with the senses, in one step, without the need for an explicit logical operation or for treating the negating word any differently than any other words. Visualizing negation as a trajectory in perceptual simulation space is explored in detail, and the implications for artificial intelligence, embodied computational models, and more practical implications of everyday use of negations are discussed.

  13. Ruptured ectopic pregnancy with a negative urine pregnancy test.

    Science.gov (United States)

    Hughes, Mallory; Lupo, Andrew; Browning, Adrianne

    2017-01-01

    Ectopic pregnancy is commonly seen as a differential diagnosis of first-trimester vaginal bleeding. Often the diagnosis is made based on a combination of exam findings, transvaginal ultrasound, and a positive pregnancy test. Our case describes a patient with a history of ectopic pregnancy treated with methotrexate and serial human chorionic gonadotropin measurements that were decreasing appropriately. At the time of evaluation, her urine pregnancy test was negative; however, she was confirmed to have a ruptured tubal ectopic pregnancy. This case highlights the variable presentation of ectopic pregnancies and the importance of combining exam findings with ultrasound and laboratory results.

  14. Expression of Androgen Receptor Is Negatively Regulated By p53

    OpenAIRE

    Fatouma Alimirah; Ravichandran Panchanathan; Jianming Chen; Xiang Zhang; Shuk-Mei Ho; Divaker Choubey

    2007-01-01

    Increased expression of androgen receptor (AR) in prostate cancer (PC) is associated with transition to androgen independence. Because the progression of PC to advanced stages is often associated with the loss of p53 function, we tested whether the p53 could regulate the expression of AR gene. Here we report that p53 negatively regulates the expression of AR in prostate epithelial cells (PrECs). We found that in LNCaP human prostate cancer cells that express the wild-type p53 and AR and in hu...

  15. The Interplay Among Children's Negative Family Representations, Visual Processing of Negative Emotions, and Externalizing Symptoms.

    Science.gov (United States)

    Davies, Patrick T; Coe, Jesse L; Hentges, Rochelle F; Sturge-Apple, Melissa L; van der Kloet, Erika

    2017-02-25

    This study examined the transactional interplay among children's negative family representations, visual processing of negative emotions, and externalizing symptoms in a sample of 243 preschool children (Mage  = 4.60 years). Children participated in three annual measurement occasions. Cross-lagged autoregressive models were conducted with multimethod, multi-informant data to identify mediational pathways. Consistent with schema-based top-down models, negative family representations were associated with attention to negative faces in an eye-tracking task and their externalizing symptoms. Children's negative representations of family relationships specifically predicted decreases in their attention to negative emotions, which, in turn, was associated with subsequent increases in their externalizing symptoms. Follow-up analyses indicated that the mediational role of diminished attention to negative emotions was particularly pronounced for angry faces. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

  16. Personality Moderates the Interaction between Positive and Negative Daily Events Predicting Negative Affect and Stress.

    Science.gov (United States)

    Longua, Julie; Dehart, Tracy; Tennen, Howard; Armeli, Stephen

    2009-08-01

    A 30-day diary study examined personality moderators (neuroticism and extraversion) of the interaction between positive and negative daily events predicting daily negative affect and night-time stress. Multilevel analyses revealed positive daily events buffered the effect of negative daily events on negative affect for individuals low in neuroticism and individuals high in extraversion, but not for individuals high in neuroticism or individuals low in extraversion. Positive daily events also buffered the effect of negative daily events on that night's stress, but only for participants low in neuroticism. As such, this research linked today's events to tonight's stressfulness. This study advances our understanding of how neuroticism and extraversion influence within-person associations between positive and negative events predicting negative affect and stress.

  17. Realism’s understanding of negative numbers

    Directory of Open Access Journals (Sweden)

    Bojanić Petar

    2016-01-01

    Full Text Available Our topic is the understanding of the nature of negative numbers - the entities to which expressions such as ‘-1’ refer. Following Frege, we view positive whole numbers as providing the answer to the question „how many?“ In this light, how are we to view negative numbers? Both positive and negative numbers can be ordered through the relation of larger or smaller. It is then true of all negative numbers that they are entities which are (somehow smaller than zero. For many, this has been understood as an ontological paradox: how can something be „less than nothing?“ Some propose to avoid the paradox by treating negative numbers as mere façons de parler. In this paper, we propose a more realist account, taking as our starting point the thesis that there is at least one familiar type of object, the magnitude of which can be expressed with negative numbers, namely, debt. How can the sense of an expression be ontologically paradoxical, yet the expression itself still plausibly refer to a social object such as a debt? Or, put differently, how is it possible to be, at the same time, a realist in financial theory and a nominalist in mathematical theory? The paper first shows that the paradox arises when the two distinct ways in which negative numbers are connected to real objects are run together. The first of the two refers to debt only, whereas the second could refer to debt, as well as to physical objects. Finally, we claim that a debt is at once a specifically social object and part of reality as described by physics.

  18. [Negative hallucination, self-onsciousness and ageing].

    Science.gov (United States)

    Hazif-Thomas, C; Stephan, F; Walter, M; Thomas, P

    2015-04-01

    Negative hallucinations are characterized by a defect in perception of an object or a person, or a denial of the existence of their perception. Negative hallucinations create blank spaces, due to both an impossible representation and an incapability of investment in reality. They have a close relationship with Cotard's syndrome, delusional theme of organ denial observed in melancholic syndromes in the elderly. Phenomenological approach. The phenomenology of negative hallucinations provides quite an amount of information on the origin of the psychotic symptoms when one is rather old. The connections between hallucinations, mood disorders and negative symptoms are often difficult to live with for the nearest and dearest. Negative hallucinations require a strict approach to identify their expression that is crucial because a wide heterogeneity exists within the pathological pictures, as in Cotard's syndrome. Although the negative hallucination has an anti traumatic function in elderly people fighting against mental pain, it still represents a deficiency in symbolization. The prevalence of this symptom is without doubt underestimated, although its presence often underlines thymic suffering that is more striking. These hallucinatory symptoms have an important impact on the patients' daily life, and they appear to be prisoners of a suffering, which cannot be revealed. We propose in this article to review the clinical symptoms of negative hallucinations in the elderly and the way to manage them. The medicinal approaches are not always effective. A greater place must be given to what is in connection with the body, aiming at a strong impact and thus to offer non-pharmacological approaches, such as somatic ones, which can be either invasive (electroconvulsive therapy) or not (transcranial magnetic stimulation). Copyright © 2014. Published by Elsevier Masson SAS.

  19. Detecting negative ions on board small satellites

    Science.gov (United States)

    Lepri, S. T.; Raines, J. M.; Gilbert, J. A.; Cutler, J.; Panning, M.; Zurbuchen, T. H.

    2017-04-01

    Recent measurements near comets, planets, and their satellites have shown that heavy ions, energetic neutral atoms, molecular ions, and charged dust contain a wealth of information about the origin, evolution, and interaction of celestial bodies with their space environment. Using highly sensitive plasma instruments, positively charged heavy ions have been used to trace exospheric and surface composition of comets, planets, and satellites as well as the composition of interplanetary and interstellar dust. While positive ions dominate throughout the heliosphere, negative ions are also produced from surface interactions. In fact, laboratory experiments have shown that oxygen released from rocky surfaces is mostly negatively charged. Negative ions and negatively charged nanograins have been detected with plasma electron analyzers in several different environments (e.g., by Cassini and Rosetta), though more extensive studies have been challenging without instrumentation dedicated to negative ions. We discuss an adaptation of the Fast Imaging Plasma Spectrometer (FIPS) flown on MErcury Surface, Space ENvironment, GEochemistry and Ranging (MESSENGER) for the measurement of negatively charged particles. MESSENGER/FIPS successfully measured the plasma environment of Mercury from 2011 until 2015, when the mission ended, and has been used to map multiple ion species (H+ through Na+ and beyond) throughout Mercury's space environment. Modifications to the existing instrument design fits within a 3U CubeSat volume and would provide a low mass, low power instrument, ideal for future CubeSat or distributed sensor missions seeking, for the first time, to characterize the contribution of negative particles in the heliospheric plasmas near the planets, moons, comets, and other sources.

  20. [Mutual inhibition between positive and negative emotions].

    Science.gov (United States)

    Shimokawa, A

    1994-02-01

    The purpose of this study is to examine the relationship between positive and negative emotions. In study 1, 62 emotional items were selected in order to measure subjective emotional experiences. In study 2, comics, photos and poems were randomly presented to 1,220 college students to induce emotion. Subjects were asked to rate their momentary emotional intensity on two set of 5-point scales (general emotional intensity scale and 62 specific emotional intensity scale). In analysis 1, positive correlations were suggested between general emotional intensity scale and some of the specific emotional intensity scales which were activated by stimuli. In analysis 2, 10 positive and 10 negative emotional items were extracted from 62 items by factor analysis. In analysis 3, 4 and 5, it became clear that the distribution of frequency of correlations of 10 positive x 10 negative items changed according to the general emotional intensity scale. That is, from low to moderate levels of GEIS, the two kinds of emotion had no or slightly positive correlation, but at high level they became to be negatively correlated. From the facts described above, it is concluded that positive and negative emotions is not always independent, but show mutual inhibition in case of high intensity level of one of each emotions.

  1. Negative obstacle detection by thermal signature

    Science.gov (United States)

    Matthies, Larry; Rankin, A.

    2003-01-01

    Detecting negative obstacles (ditches, potholes, and other depressions) is one of the most difficult problems in perception for autonomous, off-road navigation. Past work has largely relied on range imagery, because that is based on the geometry of the obstacle, is largely insensitive to illumination variables, and because there have not been other reliable alternatives. However, the visible aspect of negative obstacles shrinks rapidly with range, making them impossible to detect in time to avoid them at high speed. To relive this problem, we show that the interiors of negative obstacles generally remain warmer than the surrounding terrain throughout the night, making thermal signature a stable property for night-time negative obstacle detection. Experimental results to date have achieved detection distances 45% greater by using thermal signature than by using range data alone. Thermal signature is the first known observable with potential to reveal a deep negative obstacle without actually seeing far into it. Modeling solar illumination has potential to extend the usefulness of thermal signature through daylight hours.

  2. Exclusion of identification by negative superposition

    Directory of Open Access Journals (Sweden)

    Takač Šandor

    2012-01-01

    Full Text Available The paper represents the first report of negative superposition in our country. Photo of randomly selected young, living woman was superimposed on the previously discovered female skull. Computer program Adobe Photoshop 7.0 was used in work. Digitilized photographs of the skull and face, after uploaded to computer, were superimposed on each other and displayed on the monitor in order to assess their possible similarities or differences. Special attention was payed to matching the same anthropometrical points of the skull and face, as well as following their contours. The process of fitting the skull and the photograph is usually started by setting eyes in correct position relative to the orbits. In this case, lower jaw gonions go beyond the face contour and gnathion is highly placed. By positioning the chin, mouth and nose their correct anatomical position cannot be achieved. All the difficulties associated with the superposition were recorded, with special emphasis on critical evaluation of work results in a negative superposition. Negative superposition has greater probative value (exclusion of identification than positive (possible identification. 100% negative superposition is easily achieved, but 100% positive - almost never. 'Each skull is unique and viewed from different perspectives is always a new challenge'. From this point of view, identification can be negative or of high probability.

  3. Gender differences in negative reinforcement smoking expectancies.

    Science.gov (United States)

    Pang, Raina D; Zvolensky, Michael J; Schmidt, Norman B; Leventhal, Adam M

    2015-06-01

    Previous research suggests that females may be more motivated to smoke for negative reinforcement (NR) than males. However, it remains unclear whether gender differences in smoking outcome expectancies for negative smoking reinforcement-an important theoretical and clinical target defined as beliefs that smoking alleviates negative affect-exist above and beyond gender differences in depression and/or other outcome expectancies. Relations between gender and negative smoking reinforcement expectancies were examined in two independent samples. Sample 1 consisted of non-treatment seeking daily smokers (Male n = 188; Female n = 91) recruited from Southern California (49.5% Black, 32.2% Caucasian, and 18.3% other race/ethnicity). Sample 2 consisted of treatment seeking daily smokers (Male n = 257; Female n = 237) in Northern Florida and Vermont (10.7% Black, 82.9% Caucasian, and 6.4% other). Females (vs. males) reported stronger NR smoking expectancies with and without statistically controlling for nicotine dependence, other smoking expectancies, and anxiety and depression in both samples (βs = .06 to .14, ps = .06 to gender-specific etiological process disproportionately prominent in women. Enhancing ability to cope with negative affect without smoking or challenge NR expectancies may be particularly important for cessation treatment in women. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. The talking language in some major Gram-negative bacteria.

    Science.gov (United States)

    Banerjee, Goutam; Ray, Arun Kumar

    2016-08-01

    Cell-cell interaction or quorum sensing (QS) is a vital biochemical/physiological process in bacteria that is required for various physiological functions, including nutrient uptake, competence development, biofilm formation, sporulation, as well as for toxin secretion. In natural environment, bacteria live in close association with other bacteria and interaction among them is crucial for survival. The QS-regulated gene expression in bacteria is a cell density-dependent process and the initiation process depends on the threshold level of the signaling molecule, N-acyl-homoserine lactone (AHL). The present review summarizes the QS signal and its respective circuit in Gram-negative bacteria. Most of the human pathogens belong to Gram-negative group, and only a few of them cause disease through QS system. Thus, inhibition of pathogenic bacteria is important. Use of antibiotics creates a selective pressure (antibiotics act as natural selection factor to promote one group of bacteria over another group) for emerging multidrug-resistant bacteria and will not be suitable for long-term use. The alternative process of inhibition of QS in bacteria using different natural and synthetic molecules is called quorum quenching. However, in the long run, QS inhibitors or blockers may also develop resistance, but obviously it will solve some sort of problems. In this review, we also have stated the mode of action of quorum-quenching molecule. The understanding of QS network in pathogenic Gram-negative bacteria will help us to solve many health-related problems in future.

  5. Mental Models for the Negation of Conjunctions and Disjunctions

    Directory of Open Access Journals (Sweden)

    Guillermo Macbeth

    2014-02-01

    Full Text Available This study investigates why reasoning that involves negation is extremely difficult. We presented participants with reasoning problems containing sentences with negation of conjunctions and disjunctions in order to test predictions derived from the Mental Models Theory of human thought. According to this theory, reasoning consists of representing and comparing possibilities. Different sentential forms would require different cognitive demands. In particular, responses to a sentential negation task would be modulated by working memory load. This prediction would hold for correct responses but also for the general pattern of responses that includes incorrect responses when the task offers different response options. A within-subjects experimental design with selection paradigm was applied to test these predictions. Experimental comparisons and a complementary descriptive study yielded evidence consistent with the theory-driven predictions derived from the Mental Models Theory. The working memory load was critical for the modulation of correct responses and overall responses. We discussed alternative accounts, and suggested additional predictions for further evaluation of these phenomena.

  6. Transformation media with negative refractive indices

    Science.gov (United States)

    Chan, C. T.; Lai, Y.; Chen, H. Y.; Ng, Jack; Zhang, Z. Q.

    2009-03-01

    Artificially structured materials with a negative refractive index designed by transformation optics can have interesting properties. Based on merging the concept of complementary media and transformation media, we propose an invisibility cloak operating at a finite frequency that can make an object invisible with a pre-specified shape and size within a certain distance outside the shell. The cloak is comprised of a dielectric core, a negative index metamaterial shell and an ``anti-object'' embedded inside the shell. The cloaked object is not blinded by the cloaking shell since it lies outside the cloak. Full-wave simulations in two dimensions have been performed to verify the cloaking effect. We also show that a positive index core coated with a negative index shell can result in a frequency selective super-absorber which has an absorption cross section that is significantly higher than the geometric cross section.

  7. Goffman, Parsons, and the Negational Self

    Directory of Open Access Journals (Sweden)

    James J. Chriss

    2015-01-01

    Full Text Available Erving Goffman’s emphasis on impression management in everyday life means that for the most part persons offer only partial or incomplete glimpses of themselves. Indeed, under specifiable conditions self-presentations may take the form of a negational self. If negational selves exist at the person or individual level, then they must also exist at the collective level (that is, if we are to take seriously such notions as the social mind, collective representations, or even culture. Understandings of how this negational self appears and is produced at various analytical levels (micro, meso, and macro can be anchored via a conceptual schema which merges Goffman’s own identity typology with the three-world model of Jürgen Habermas by way of Talcott Parsons.

  8. [H. pylori-negative gastric cancer].

    Science.gov (United States)

    Kato, Mototsugu; Ono, Shouko; Shimizu, Yuichi; Sakamoto, Naoya; Mabe, Katsuhiro

    2015-07-01

    Broad category of H. pylori-negative gastric cancer includes true gastric cancer without history of H. pylori infection, gastric cancer after successful eradication of H. pylori, and H. pylori-negative gastric cancer with history of H. pylori infection. The frequency of gastric cancer without history of H. pylori infection was less than 1% in Japan. Although preventive effect for gastric cancer of H. pylori eradication can be expected, risk of gastric cancer incidence continues after eradication of H. pylori. The frequency of gastric cancer after successful eradication has been increasing, since eradication treatment was widely spread in Japan. The features of H. pylori-negative gastric cancer were reported to be different from conventional H. pylori-positive gastric cancer. Endoscopic screening of gastric cancer requires to understand the characteristics of gastric cancer based on status of H. pylori infection.

  9. Classical fluids of negative heat capacity

    Energy Technology Data Exchange (ETDEWEB)

    Landsberg, P.T. (Southampton Univ., (United Kingdom). Faculty of Mathematical Studies); Woodard, R.P. (Florida Univ., Gainesville, FL (United States). Dept. of Physics)

    1992-06-01

    It is shown that new parameters X can be defined such that the heat capacity C{sub X} {equivalent to} T({partial derivative}S/{partial derivative}T)X is negative, even when the canonical ensemble (i.e. at fixed T = ({partial derivative}U/{partial derivative}S) and Y {ne} X) is stable. As examples we treat black body radiation and general gas systems with nonsingular {kappa}{sub T}. For the case of a simple ideal gas we even exhibit an apparatus which enforces a constraint X(p,V) = const. that makes C{sub X} < 0. Since it is possible to invent constraints for which canonically stable systems have negative heat capacity we speculate that it may also be possible to infer the statistical mechanics of canonically unstable systems - for which even the traditional heat capacities are negative - by imposing constraints that stabilize the associated, inoncanonical ensembles.

  10. Classical fluids of negative heat capacity

    Energy Technology Data Exchange (ETDEWEB)

    Landsberg, P.T. [Southampton Univ., (United Kingdom). Faculty of Mathematical Studies; Woodard, R.P. [Florida Univ., Gainesville, FL (United States). Dept. of Physics

    1992-06-01

    It is shown that new parameters X can be defined such that the heat capacity C{sub X} {equivalent_to} T({partial_derivative}S/{partial_derivative}T)X is negative, even when the canonical ensemble (i.e. at fixed T = ({partial_derivative}U/{partial_derivative}S) and Y {ne} X) is stable. As examples we treat black body radiation and general gas systems with nonsingular {kappa}{sub T}. For the case of a simple ideal gas we even exhibit an apparatus which enforces a constraint X(p,V) = const. that makes C{sub X} < 0. Since it is possible to invent constraints for which canonically stable systems have negative heat capacity we speculate that it may also be possible to infer the statistical mechanics of canonically unstable systems - for which even the traditional heat capacities are negative - by imposing constraints that stabilize the associated, inoncanonical ensembles.

  11. News Media Framing of Negative Campaigning

    DEFF Research Database (Denmark)

    Pedersen, Rasmus Tue

    2014-01-01

    News media coverage of election campaigns is often characterized by use of the strategic game frame and a focus on politicians’ use of negative campaigning. However, the exact relationship between these two characteristics of news coverage is largely unexplored. This article theorizes that consumer...... demand and norms of journalistic independence might induce the news media outlets to cover negative campaigning with a strategic game frame. A comprehensive content analysis based on several newspaper types, several election campaigns, and several different measurements of media framing confirms...... that news coverage of negative campaigning does apply the strategic game frame to a significantly larger degree than articles covering positive campaigning. This finding has significant implications for campaigning politicians and for scholars studying campaign and media effects....

  12. Emotionally negative pictures enhance gist memory.

    Science.gov (United States)

    Bookbinder, S H; Brainerd, C J

    2017-02-01

    In prior work on how true and false memory are influenced by emotion, valence and arousal have often been conflated. Thus, it is difficult to say which specific effects are caused by valence and which are caused by arousal. In the present research, we used a picture-memory paradigm that allowed emotional valence to be manipulated with arousal held constant. Negatively valenced pictures elevated both true and false memory, relative to positive and neutral pictures. Conjoint recognition modeling revealed that negative valence (a) reduced erroneous suppression of true memories and (b) increased the familiarity of the semantic content of both true and false memories. Overall, negative valence impaired the verbatim side of episodic memory but enhanced the gist side, and these effects persisted even after a week-long delay. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  13. Giant negative thermal expansion in magnetic nanocrystals

    Science.gov (United States)

    Zheng, X. G.; Kubozono, H.; Yamada, H.; Kato, K.; Ishiwata, Y.; Xu, C. N.

    2008-12-01

    Most solids expand when they are heated, but a property known as negative thermal expansion has been observed in a number of materials, including the oxide ZrW2O8 (ref. 1) and the framework material ZnxCd1-x(CN)2 (refs 2,3). This unusual behaviour can be understood in terms of low-energy phonons, while the colossal values of both positive and negative thermal expansion recently observed in another framework material, Ag3[Co(CN)6], have been explained in terms of the geometric flexibility of its metal-cyanide-metal linkages. Thermal expansion can also be stopped in some magnetic transition metal alloys below their magnetic ordering temperature, a phenomenon known as the Invar effect, and the possibility of exploiting materials with tuneable positive or negative thermal expansion in industrial applications has led to intense interest in both the Invar effect and negative thermal expansion. Here we report the results of thermal expansion experiments on three magnetic nanocrystals-CuO, MnF2 and NiO-and find evidence for negative thermal expansion in both CuO and MnF2 below their magnetic ordering temperatures, but not in NiO. Larger particles of CuO and MnF2 also show prominent magnetostriction (that is, they change shape in response to an applied magnetic field), which results in significantly reduced thermal expansion below their magnetic ordering temperatures; this behaviour is not observed in NiO. We propose that the negative thermal expansion effect in CuO (which is four times larger than that observed in ZrW2O8) and MnF2 is a general property of nanoparticles in which there is strong coupling between magnetism and the crystal lattice.

  14. Automatic negation detection in narrative pathology reports.

    Science.gov (United States)

    Ou, Ying; Patrick, Jon

    2015-05-01

    To detect negations of medical entities in free-text pathology reports with different approaches, and evaluate their performances. Three different approaches were applied for negation detection: the lexicon-based approach was a rule-based method, relying on trigger terms and termination clues; the syntax-based approach was also a rule-based method, where the rules and negation patterns were designed using the dependency output from the Stanford parser; the machine-learning-based approach used a support vector machine as a classifier to build models with a number of features. A total of 284 English pathology reports of lymphoma were used for the study. The machine-learning-based approach had the best overall performance on the test set with micro-averaged F-score of 82.56%, while the syntax-based approach performed worst with 78.62% F-score. The lexicon-based approach attained an overall average precision of 89.74% and recall of 76.09%, which were significantly better than the results achieved by Negation Tagger with a similar approach. The lexicon-based approach benefitted from being customized to the corpus more than the other two methods. The errors in negation detection with the syntax-based approach producing poorest performance were mainly due to the poor parsing results, and the errors with the other methods were probably because of the abnormal grammatical structures. A machine-learning-based approach has potential advantages for negation detection, and may be preferable for the task. To improve the overall performance, one of the possible solutions is to apply different approaches to each section in the reports. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Negative electrodes for lithium cells and batteries

    Science.gov (United States)

    Vaughey, John T.; Fransson, Linda M.; Thackeray, Michael M.

    2005-02-15

    A negative electrode is disclosed for a non-aqueous electrochemical cell. The electrode has an intermetallic compound as its basic structural unit with the formula M.sub.2 M' in which M and M' are selected from two or more metal elements including Si, and the M.sub.2 M' structure is a Cu.sub.2 Sb-type structure. Preferably M is Cu, Mn and/or Li, and M' is Sb. Also disclosed is a non-aqueous electrochemical cell having a negative electrode of the type described, an electrolyte and a positive electrode. A plurality of cells may be arranged to form a battery.

  16. Negative Ion Sources: Magnetron and Penning

    CERN Document Server

    Faircloth, D.C.

    2013-12-16

    The history of the magnetron and Penning electrode geometry is briefly outlined. Plasma generation by electrical discharge-driven electron impact ionization is described and the basic physics of plasma and electrodes relevant to magnetron and Penning discharges are explained. Negative ions and their applications are introduced, along with their production mechanisms. Caesium and surface production of negative ions are detailed. Technical details of how to build magnetron and Penning surface plasma sources are given, along with examples of specific sources from around the world. Failure modes are listed and lifetimes compared.

  17. Indlæring af negative tal

    OpenAIRE

    Damm, Jakob; Krabbe, Elisabeth; Nissen, Rie

    2006-01-01

    I denne rapport ses på indlæring af negative tal som en case i indlæringsvanskelighederne i matematikundervisningen i 4. – 6. klasse. Problemstillingen belyses fra to vinkler. Der ses på casen fra et historisk perspektiv, hvor der gives en kort introduktion af de negative tals udvikling og plads i historien. Her følger nogle forslag til, hvordan historien kan bruges i undervisningen. Casen belyses også fra et psykologisk perspektiv, hvor Piaget, Vygotsky og Sfards teorier kort introducere...

  18. Soft Manifold Dynamics behind Negative Thermal Expansion

    Science.gov (United States)

    Schlesinger, Z.; Rosen, J. A.; Hancock, J. N.; Ramirez, A. P.

    2008-07-01

    Minimal models are developed to examine the origin of large negative thermal expansion in underconstrained systems. The dynamics of these models reveals how underconstraint can organize a thermodynamically extensive manifold of low-energy modes which not only drives negative thermal expansion but extends across the Brillioun zone. Mixing of twist and translation in the eigenvectors of these modes, for which in ZrW2O8 there is evidence from infrared and neutron scattering measurements, emerges naturally in our model as a signature of the dynamics of underconstraint.

  19. Negative-Index Media for Matter Waves

    Science.gov (United States)

    Perales, F.; Bocvarski, V.; Baudon, J.; Hamamda, M.; Grucker, J.; Dutier, G.; Mainos, C.; Boustimi, M.; Ducloy, M.

    2010-02-01

    One reviews the recently introduced field of matter-wave "meta-optics", i.e. the extension of optical negative-index media (NIM) to atom optics. After emphasizing the differences with light meta-optics and particularly the necessary transient character of NIM's in atom optics, we present the way of generating matter-wave NIM's and their general properties: negative refraction, atom meta-lenses. Finally their specific features are reviewed: longitudinal wave packet narrowing associated to a time-reversal effect, transient revivals of evanescent matter waves and atom reflection echoes at a potential barrier.

  20. Expression of Androgen Receptor Is Negatively Regulated By p53

    Directory of Open Access Journals (Sweden)

    Fatouma Alimirah

    2007-12-01

    Full Text Available Increased expression of androgen receptor (AR in prostate cancer (PC is associated with transition to androgen independence. Because the progression of PC to advanced stages is often associated with the loss of p53 function, we tested whether the p53 could regulate the expression of AR gene. Here we report that p53 negatively regulates the expression of AR in prostate epithelial cells (PrECs. We found that in LNCaP human prostate cancer cells that express the wild-type p53 and AR and in human normal PrECs, the activation of p53 by genotoxic stress or by inhibition of p53 nuclear export downregulated the expression of AR. Furthermore, forced expression of p53 in LNCaP cells decreased the expression of AR. Conversely, knockdown of p53 expression in LNCaP cells increased the AR expression. Consistent with the negative regulation of AR expression by p53, the p53-null HCT116 cells expressed higher levels of AR compared with the isogenic HCT116 cells that express the wildtype p53. Moreover, we noted that in etoposide treated LNCaP cells p53 bound to the promoter region of the AR gene, which contains a potential p53 DNA-binding consensus sequence, in chromatin immunoprecipitation assays. Together, our observations provide support for the idea that the loss of p53 function in prostate cancer cells contributes to increased expression of AR.

  1. Negative Expression of Melanoma Cell Adhesion Molecule (MCAM Correlated with Axillary Lymph Node Metastasis in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sartika Nurwenda

    2016-09-01

    Full Text Available Triple negative breast cancer (TNBC is breast cancer that demonstrate the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. TNBC has an aggressive behaviour, high frequency of metastasis to the axillary lymph nodes and recurrence, and poor prognosis. Metastasis to the axillary lymph nodes will affect the rate of survival and recurrence in TNBC. Melanoma cell adhession molecule (MCAM is a membrane glycoprotein of the immunoglobulin superfamily, which is involved in the cells binding, which later became known as the marker for the progression and metastasis of melanoma and carcinoma of the prostate. However, MCAM role in mammary carcinoma still controversial. The aim of this study was to assess correlation between MCAM expression with incidence of metastatic to axillary lymph nodes in TNBC. This research was conducted during January 1st 2010–April 31st 2015 at Pathology Anatomy, Faculty of Medicine, Universitas Padjadjaran. This study used a cross-sectional design, using lambda correlation test. MCAM immunohistochemical staining performed on 56 samples of paraffin blocks of TNBC group that did not metastasized and has metastasized to the axillary lymph nodes. A total of 22 of 28 (78.6% of TNBC metastatic to axillary lymph nodes have histoskor MCAM value <4 (negative, whereas 16 of 28 (57.1% of TNBC non-metastatic have histoskor value ≥ 4 (positive. Negative expression of MCAM correlated with TNBC that had metastasized to axillary lymph nodes, although not the only factor that influenced them.

  2. Negative thermal expansion in framework compounds

    Indian Academy of Sciences (India)

    electron microscopy, EXAFS and differential scanning calorimetry have been used to study structural properties as a function of temperature for these compounds. In this paper we report the results obtained from our study [14–20] of negative thermal expansion (NTE) compounds with chemical compositions of NX2O8 and.

  3. THE SISYPHEAN MYTH, NEGATIVE CAPABILITY AND SOCIETAL ...

    African Journals Online (AJOL)

    mycl

    literature can offer. But not all literary expressions are posers of questions and problems. Certain concepts such as Keats' Negative. Capability suggest solutions to Camus' Sisyphean problem and its ilk. This paper explores this problem-solution relationship and finds complementarity and possibility feasible. Introduction.

  4. Negative Interpersonal Interactions in Student Training Settings

    Science.gov (United States)

    Ferris, Patricia A.; Kline, Theresa J. B.

    2009-01-01

    Studies demonstrate that negative interpersonal interaction(s) (NII) such as bullying are frequent and harmful to individuals in workplace and higher education student settings. Nevertheless, it is unclear whether the degree of perceived severity of NII varies by the status of the actor. The present study explored the moderating effect of actor…

  5. Targeting EGFR in Triple Negative Breast Cancer

    OpenAIRE

    Naoto T. Ueno, Dongwei Zhang

    2011-01-01

    Our preliminary data show that erlotinib inhibits Triple-negative breast cancer (TNBC) in a xenograft model. However, inhibition of metastasis by erlotinib is accompanied by nonspecific effects because erlotinib can inhibit other kinases; thus, more direct targets that regulate TNBC metastasis need to be identified to improve its therapeutic efficacy.

  6. Targeting EGFR in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Naoto T. Ueno, Dongwei Zhang

    2011-01-01

    Full Text Available Our preliminary data show that erlotinib inhibits Triple-negative breast cancer (TNBC in a xenograft model. However, inhibition of metastasis by erlotinib is accompanied by nonspecific effects because erlotinib can inhibit other kinases; thus, more direct targets that regulate TNBC metastasis need to be identified to improve its therapeutic efficacy.

  7. Magnetic levitation induced by negative permeability

    OpenAIRE

    Rangelov, A. A.

    2011-01-01

    In this paper we study the interaction between a point magnetic dipole and a semi-infinite metamaterial using the method of images. We obtain analytical expressions for the levitation force for an arbitrarily oriented dipole. Surprisingly the maximal levitation force for negative permeability is found to be stronger compared to the case when the dipole is above a superconductor.

  8. Negative emotions impact on mental physical health

    Directory of Open Access Journals (Sweden)

    Oblitas, Luis Armando

    2009-12-01

    Full Text Available Fear, sadness, anger and disgust are considered affective states, that when they become frequent and intense, adversely affect the quality of life. Consequently, negative emotions are regarded as one of the key risk factors in physical and mental illness. Firstly, this article aims to define precisely concepts and key features of each emotion. The second objective of this paper is to show a synthesis of scientific findings supporting the influence of emotional factors, especially classic negative emotions in the process of health and disease. These psychophysiological phenomena have been associated with mental and physical illness as influencing variables in its initiation, development and maintenance. Therefore, the paper reviews some of the links between these four negative emotions and mental disorders. It also reviews the evidence supporting the influence of negative emotions in the development of risk behaviors to physical health. Finally, we describe some data supporting the impact of psychophysiological activation of emotions in organic systems, such as, for instance, immunity, tumor processes and so on

  9. The Contrast Theory of negative input.

    Science.gov (United States)

    Saxton, M

    1997-02-01

    Beliefs about whether or not children receive corrective input for grammatical errors depend crucially on how one defines the concept of correction. Arguably, previous conceptualizations do not provide a viable basis for empirical research (Gold, 1967; Brown & Hanlon, 1970; Hirsh-Pasek, Treiman & Schneiderman, 1984). Within the Contrast Theory of negative input, an alternative definition of negative evidence is offered, based on the idea that the unique discourse structure created in the juxtaposition of child error and adult correct form can reveal to the child the contrast, or conflict, between the two forms, and hence provide a basis for rejecting the erroneous form. A within-subjects experimental design was implemented for 36 children (mean age 5;0), in order to compare the immediate effects of negative evidence with those of positive input, on the acquisition of six novel irregular past tense forms. Children reproduced the correct irregular model more often, and persisted with fewer errors, following negative evidence rather than positive input.

  10. Quantum Heat Engine and Negative Boltzmann Temperature

    Science.gov (United States)

    Xi, Jing-Yi; Quan, Hai-Tao

    2017-09-01

    To clarify the ambiguity on negative Boltzmann temperature in literature, we study the Carnot and the Otto cycle with one of the heat reservoirs at the negative Boltzmann temperature based on a canonical ensemble description. The work extraction, entropy production and the efficiency of these cycles are explored. Conditions for constructing and properties of these thermodynamic cycles are elucidated. We find that the apparent “violation” of the second law of thermodynamics in these cycles are due to the fact that the traditional definition of thermodynamic efficiency is inappropriate in this situation. When properly understanding the efficiency and the adiabatic processes, in which the system crosses over “absolute ZERO” in a limit sense, the Carnot cycle with one of the heat reservoirs at a negative Boltzmann temperature can be understood straightforwardly, and it contradicts neither the second nor the third law of thermodynamics. Hence, negative Boltzmann temperature is a consistent concept in thermodynamics. We use a two-level system and an Ising spin system to illustrate our central results. Support from the National Science Foundation of China under Grants Nos. 11375012, 11534002, and The Recruitment Program of Global Youth Experts of China

  11. Performance characteristics of positive and negative delayed ...

    Indian Academy of Sciences (India)

    Cochin University of Science and Technology, Cochin 682 022, India ... press chaotic dynamics and bistabily in semiconductor lasers [37,38]. The effect of such a combination in inducing chaotic dynamics through a quasiperiodic route in .... To study the effect of both positive- and negative-delayed optoelectronic feedback.

  12. Performance characteristics of positive and negative delayed ...

    Indian Academy of Sciences (India)

    The effects of positive and negative delayed optoelectronic feedback in producing chaotic outputs from such lasers with nonlinear gain reduction in its optimum ... Sophisticated Test and Instrumentation Centre; Cochin University of Science and Technology, Cochin 682 022, India; International School of Photonics, Cochin ...

  13. Error-Related Psychophysiology and Negative Affect

    Science.gov (United States)

    Hajcak, G.; McDonald, N.; Simons, R.F.

    2004-01-01

    The error-related negativity (ERN/Ne) and error positivity (Pe) have been associated with error detection and response monitoring. More recently, heart rate (HR) and skin conductance (SC) have also been shown to be sensitive to the internal detection of errors. An enhanced ERN has consistently been observed in anxious subjects and there is some…

  14. Exploring the Psychological Influence of Perceived Negative ...

    African Journals Online (AJOL)

    This paper critically examined the psychological influence of perceived negative foreign factors which were those obstacles brought to Nigeria and Nigerians since our first contact with the European colonialists. The obstacles have constituted formidable barriers to indigenous organisational performance and national ...

  15. Preservation Copying Endangered Historic Negative Collections

    DEFF Research Database (Denmark)

    Kejser, Ulla Bøgvad

    2008-01-01

    This article discusses preservation copying of unstable B&W nitrate and acetate still photographic negatives. It focuses on evaluating two different strategies for preserving the copies from a point of view of quality and cost-effectiveness. The evaluated strategies are preservation of the master...

  16. Discriminant projective non-negative matrix factorization.

    Directory of Open Access Journals (Sweden)

    Naiyang Guan

    Full Text Available Projective non-negative matrix factorization (PNMF projects high-dimensional non-negative examples X onto a lower-dimensional subspace spanned by a non-negative basis W and considers W(T X as their coefficients, i.e., X≈WW(T X. Since PNMF learns the natural parts-based representation Wof X, it has been widely used in many fields such as pattern recognition and computer vision. However, PNMF does not perform well in classification tasks because it completely ignores the label information of the dataset. This paper proposes a Discriminant PNMF method (DPNMF to overcome this deficiency. In particular, DPNMF exploits Fisher's criterion to PNMF for utilizing the label information. Similar to PNMF, DPNMF learns a single non-negative basis matrix and needs less computational burden than NMF. In contrast to PNMF, DPNMF maximizes the distance between centers of any two classes of examples meanwhile minimizes the distance between any two examples of the same class in the lower-dimensional subspace and thus has more discriminant power. We develop a multiplicative update rule to solve DPNMF and prove its convergence. Experimental results on four popular face image datasets confirm its effectiveness comparing with the representative NMF and PNMF algorithms.

  17. Monogamy Relations for Squared Entanglement Negativity

    Science.gov (United States)

    Liu, Feng

    2016-10-01

    This paper contains two main contents. In the first part, we provide two counterexamples of monogamy inequalities for the squared entanglement negativity: one three-qutrit pure state which violates of the He—Vidal monogamy conjecture, and one four-qubit pure state which disproves the squared-negativity-based Regula—Martino—Lee—Adesso-class strong monogamy conjecture. In the second part, we investigate the sharing of the entanglement negativity in a composite cavity-reservoir system using the corresponding multipartite entanglement scores, and then we find that there is no simple dominating relation between multipartite entanglement scores and the entanglement negativity in composite cavity-reservoir systems. As a by-product, we further validate that the entanglement of two cavity photons is a decreasing function of the evolution time, and the entanglement will suddenly disappear interacting with independent reservoirs. Supported by the National Natural Science Foundation of China under Grant No. 60973135 and Shandong Provincial Natural Science Foundation of China under Grant No. ZR2015FQ006

  18. Negative Life Events Scale for Students (NLESS)

    Science.gov (United States)

    Buri, John R.; Cromett, Cristina E.; Post, Maria C.; Landis, Anna Marie; Alliegro, Marissa C.

    2015-01-01

    Rationale is presented for the derivation of a new measure of stressful life events for use with students [Negative Life Events Scale for Students (NLESS)]. Ten stressful life events questionnaires were reviewed, and the more than 600 items mentioned in these scales were culled based on the following criteria: (a) only long-term and unpleasant…

  19. On affine non-negative matrix factorization

    DEFF Research Database (Denmark)

    Laurberg, Hans; Hansen, Lars Kai

    2007-01-01

    We generalize the non-negative matrix factorization (NMF) generative model to incorporate an explicit offset. Multiplicative estimation algorithms are provided for the resulting sparse affine NMF model. We show that the affine model has improved uniqueness properties and leads to more accurate id...

  20. Variations of Negative Pressure Wound Therapy

    African Journals Online (AJOL)

    There have been several reports about the various types of negative pressure wound therapy. (NPWT). The most common dressing material is the polyurethane foam sponge, although there have been some reports that did not use any dressing materials.[1] Even for the polyurethane foam sponges, there are wide variations ...

  1. The negative ions emission in nitrogen

    Science.gov (United States)

    Soon, W. H.; Kunc, J. A.

    1991-01-01

    The contribution of negative atomic ions to continuum radiation in nitrogen plasma is discussed. It is shown that both unstable N(-)(3P) and metastable N(-)(1D) ions have a significant effect on the total production of the continuum radiation at electron temperatures below 12,000 K.

  2. Positive and negative pulsed corona in argon

    NARCIS (Netherlands)

    E.M. van Veldhuizen; W.R. Rutgers; U. Ebert (Ute)

    2002-01-01

    htmlabstractPhotographs are obtained of corona discharges in argon at atmospheric pressure using a high resolution, intensified CCD camera. Positive and negative polarity is applied at the curved electrode in a point-plane gap and a plane-plane gap with a protruding point. Branching is observed in

  3. Entanglement versus negative domains of Wigner functions

    DEFF Research Database (Denmark)

    Dahl, Jens Peder; Mack, H.; Wolf, A.

    2006-01-01

    We show that s waves, that is wave functions that only depend on a hyperradius, are entangled if and only if the corresponding Wigner functions exhibit negative domains. We illustrate this feature using a special class of s waves which allows us to perform the calculations analytically. This class...

  4. Negative freedom and the liberal paradoxes

    NARCIS (Netherlands)

    van Hees, M.V.B.P.M

    In their game-theoretic formulations, the liberal paradoxes of Amartya Sm and Alan Gibbard show a tension between freedom on the one hand, and Pareto optimality and stability on the other. This article examines what happens to the liberal paradoxes if a negative conception of freedom is used. Given

  5. Electroluminescence and negative differential resistance studies of ...

    Indian Academy of Sciences (India)

    Negative differential resistance (NDR) characteristics observed at a low voltage region in blended OLED is related to the generation of guest hopping site and phonon scattering phenomenon. However, luminescence of the devices is not altered by the NDR effect. Keywords. Organic-light-emitting diodes; Alq3; TPD; PBD; ...

  6. Electroluminescence and negative differential resistance studies of ...

    Indian Academy of Sciences (India)

    Electroluminescence properties were investigated with respect to blend systems. Significant improvement in turn-on voltage and luminance intensity was observed by employing the blends technique. Negative differential resistance (NDR) characteristics observed at a low voltage region in blended OLED is related to the ...

  7. [Negative symptoms of schizophrenia: historical aspects].

    Science.gov (United States)

    Pringuey, D; Paquin, N; Cherikh, F; Giordana, B; Belzeaux, R; Cermolacce, M; Adida, M; Azorin, J-M

    2015-12-01

    The history of negative symptoms of schizophrenia rises early days of medicine in clinical and pathophysiological differences between positive and negative and their complex joint. Forming a set of typical core of symptoms, and some feature of a syndrome belonging to a specific pathophysiological mechanism, negative symptoms of schizophrenia emerge from old descriptions of clinical pictures, related to the overall look of madness, the heart of alienation, a central sign of early dementia, gradually more precisely describing the strange nature of the autistic withdrawal and schizophrenic apragmatism. At therapeutic era, negative symptoms have taken over the positive symptoms to establish an operational criteria whose importance lies in the progressive severity of this clinical type and in their contribution to therapeutic resistance. Despite the efforts of modern typological classifications, this work rehabilitates the old concept of "unitary psychosis" by defining a common symptomatic core to multiple clinical forms of psychosis, combining deficit of emotional expression and avolition, meaning a native psychopathology and a pathophysiology possibly in a common final way, and calling the arrival of new treatment strategies. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Blood Culture-Negative Endocarditis, Morocco.

    Science.gov (United States)

    Boudebouch, Najma; Sarih, M'hammed; Chakib, Abdelfattah; Fadili, Salma; Boumzebra, Drissi; Zouizra, Zahira; Mahadji, Badie Azamane; Amarouch, Hamid; Raoult, Didier; Fournier, Pierre-Edouard

    2017-11-01

    We investigated the microorganisms causing blood culture-negative endocarditis (BCNE) in Morocco. We tested 19 patients with BCNE by serologic methods, molecular methods, or both and identified Bartonella quintana, Staphylococcus aureus, Streptococcus equi, and Streptococcus oralis in 4 patients. These results highlight the role of these zoonotic agents in BCNE in Morocco.

  9. Are there negative returns to aid?

    NARCIS (Netherlands)

    Lensink, Robert; White, Howard

    1999-01-01

    The World Bank report Assessing Aid assumes that aid is more effective when it is given to countries where polices are sound. Moreover, it assumes that an inflow of aid, above a certain level, starts to have negative effects. In this paper we empirically test both assumptions. We do not find

  10. The Positive Side of Negative Labelling

    NARCIS (Netherlands)

    Dam, van Y.K.; Jonge, de J.

    2015-01-01

    Ethical labels signal positive ethical quality of a product but fail to create massive demand for such products. Based on regulatory focus theory and prospect theory, it is argued that negative signalling of low ethical quality would have a stronger effect on the adoption of ethical products than

  11. Revisiting the gram-negative lipoprotein paradigm

    Science.gov (United States)

    The processing of lipoproteins (lpps) in Gram-negative bacteria is generally considered to be an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein n-acyltransferase. The mature lipoproteins are then sorted...

  12. Exploring the Psychological Influence of Perceived Negative ...

    African Journals Online (AJOL)

    Nneka Umera-Okeke

    2017-10-14

    Oct 14, 2017 ... Abstract. This paper critically examined the psychological influence of perceived negative foreign factors which were those obstacles brought to Nigeria and Nigerians since our first contact with the European colonialists. The obstacles have constituted formidable barriers to indigenous organisational ...

  13. Implicit and explicit negation in logic programming

    NARCIS (Netherlands)

    Jonker, C.M.

    The focus of the research is the semantics of logic programming. Concepts in the currently used semantics like negation as failure, the Closed World Assumption and multivalued interpretations need to be thoroughly understood in order to develop semantics for extensions of the logic programming

  14. Targeted chemotherapy for triple-negative breast cancers via LHRH receptor.

    Science.gov (United States)

    Föst, Crispin; Duwe, Francesca; Hellriegel, Martin; Schweyer, Stefan; Emons, Günter; Gründker, Carsten

    2011-05-01

    Triple-negative breast cancer does not express estrogen and progesterone receptors and there is no overexpression/amplification of the HER2-neu gene. Therefore, this subtype of breast cancer lacks the benefits of specific therapies which target these receptors. About 60% of all human breast cancers express receptors for luteinizing hormone releasing hormone (LHRH, GnRH), which might be used as a target. The LHRH receptor can be used for targeted chemotherapy with cytotoxic luteinizing hormone releasing hormone agonists such as AEZS-108 (AN-152), in which doxorubicin is linked to [D-Lys6]LHRH. In the present study we have analyzed by in vitro and in vivo experiments whether the cytotoxic LHRH agonist AEZS-108 (AN-152) induces apoptosis in triple-negative human breast cancer cells that express LHRH receptors. LHRH receptor expression in tumor biopsy specimens of triple-negative breast cancers was tested using immunohistochemistry. Cell proliferation was analyzed using alamar blue proliferation assay. Induction of apoptosis was quantified by measurement of loss of mitochondrial membrane potential. In vivo experiments were performed using nude mice bearing xenografted human breast tumors.Thirty-one of 42 triple-negative breast cancers (73.8%) expressed LHRH receptors. We could show that treatment of triple-negative but LHRH-positive MDA-MB-231, HCC1806 and HCC1937 human breast cancer cells with AEZS-108 (AN-152) resulted in apoptotic cell death in vitro via activation of caspase-3. The antitumor effects were confirmed in nude mice. AEZS-108 (AN-152) inhibited the growth of xenotransplants of triple-negative human breast cancers in nude mice completely, without any apparent side effects. The cytotoxic LHRH agonist AEZS-108 (AN-152) seems to be a suitable drug for an efficacious therapy for triple-negative breast cancers with little toxicity.

  15. Attentional bias to negative affect moderates negative affect's relationship with smoking abstinence.

    Science.gov (United States)

    Etcheverry, Paul E; Waters, Andrew J; Lam, Cho; Correa-Fernandez, Virmarie; Vidrine, Jennifer Irvin; Cinciripini, Paul M; Wetter, David W

    2016-08-01

    To examine whether initial orienting (IO) and inability to disengage (ITD) attention from negative affective stimuli moderate the association of negative affect with smoking abstinence during a quit attempt. Data were from a longitudinal cohort study of smoking cessation (N = 424). A negative affect modified Stroop task was administered 1 week before and on quit day to measure IO and ITD. Ecological Momentary Assessments were used to create negative affect intercepts and linear slopes for the week before quitting and on quit day. Quit day and long-term abstinence measures were collected. Continuation ratio logit model analyses found significant interactions for prequit negative affect slope with prequit ITD, odds ratio (OR) = 0.738 (0.57, 0.96), p = .02, and for quit day negative affect intercept with quit day ITD, OR = 0.62 (0.41, 950), p = .03, predicting abstinence. The Prequit Negative Affect Intercept × Prequit IO interaction predicting quit day abstinence was significant, OR = 1.42 (1.06, 1.90), p = .02, as was the Quit Day Negative Affect Slope × Quit Day IO interaction predicting long-term abstinence, OR = 1.45 (1.02, 2.08), p = .04. The hypothesis that the association of negative affect with smoking abstinence would be moderated by ITD was generally supported. Among individuals with high ITD, negative affect was inversely related to abstinence, but unrelated to abstinence among individuals with lower levels of ITD. Unexpectedly, among individuals with low IO, negative affect was inversely related to abstinence, but unrelated to abstinence among individuals with higher levels of ITD. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  16. Revisiting the Gram-negative lipoprotein paradigm.

    Science.gov (United States)

    LoVullo, Eric D; Wright, Lori F; Isabella, Vincent; Huntley, Jason F; Pavelka, Martin S

    2015-05-01

    The processing of lipoproteins (Lpps) in Gram-negative bacteria is generally considered an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein N-acyltransferase. The mature lipoproteins are then sorted by the Lol system, with most Lpps inserted into the outer membrane (OM). We demonstrate here that the lnt gene is not essential to the Gram-negative pathogen Francisella tularensis subsp. tularensis strain Schu or to the live vaccine strain LVS. An LVS Δlnt mutant has a small-colony phenotype on sucrose medium and increased susceptibility to globomycin and rifampin. We provide data indicating that the OM lipoprotein Tul4A (LpnA) is diacylated but that it, and its paralog Tul4B (LpnB), still sort to the OM in the Δlnt mutant. We present a model in which the Lol sorting pathway of Francisella has a modified ABC transporter system that is capable of recognizing and sorting both triacylated and diacylated lipoproteins, and we show that this modified system is present in many other Gram-negative bacteria. We examined this model using Neisseria gonorrhoeae, which has the same Lol architecture as that of Francisella, and found that the lnt gene is not essential in this organism. This work suggests that Gram-negative bacteria fall into two groups, one in which full lipoprotein processing is essential and one in which the final acylation step is not essential, potentially due to the ability of the Lol sorting pathway in these bacteria to sort immature apolipoproteins to the OM. This paper describes the novel finding that the final stage in lipoprotein processing (normally considered an essential process) is not required by Francisella tularensis or Neisseria gonorrhoeae. The paper provides a potential reason for this and shows that it may be widespread in other Gram-negative bacteria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. Negative ion beam extraction in ROBIN

    Energy Technology Data Exchange (ETDEWEB)

    Bansal, Gourab, E-mail: bansal@ipr.res.in [Institute for Plasma Research (IPR), Bhat, Gandhinagar, Gujarat 382428 (India); Gahlaut, Agrajit; Soni, Jignesh; Pandya, Kaushal; Parmar, Kanu G.; Pandey, Ravi; Vuppugalla, Mahesh; Prajapati, Bhavesh; Patel, Amee; Mistery, Hiren [Institute for Plasma Research (IPR), Bhat, Gandhinagar, Gujarat 382428 (India); Chakraborty, Arun; Bandyopadhyay, Mainak; Singh, Mahendrajit J.; Phukan, Arindam; Yadav, Ratnakar K.; Parmar, Deepak [ITER-India, Institute for Plasma Research, A-29, Sector 25, GIDC, Gandhinagar, Gujarat 380025 (India)

    2013-10-15

    Highlights: ► A RF based negative hydrogen ion beam test bed has been set up at IPR, India. ► Ion source has been successfully commissioned and three campaigns of plasma production have been carried out. ► Extraction system (35 kV) has been installed and commissioning has been initiated. Negative ion beam extraction is immediate milestone. -- Abstract: The RF based single driver −ve ion source experiment test bed ROBIN (Replica Of BATMAN like source in INDIA) has been set up at Institute for Plasma Research (IPR), India in a technical collaboration with IPP, Garching, Germany. A hydrogen plasma of density 5 × 10{sup 12} cm{sup −3} is expected in driver region of ROBIN by launching 100 kW RF power into the driver by 1 MHz RF generator. The cesiated source is expected to deliver a hydrogen negative ion beam of 10 A at 35 kV with a current density of 35 mA/cm{sup 2} as observed in BATMAN. In first phase operation of the ROBIN ion source, a hydrogen plasma has been successfully generated (without extraction system) by coupling 80 kW RF input power through a matching network with high power factor (cos θ > 0.8) and different plasma parameters have been measured using Langmuir probes and emission spectroscopy. The plasma density of 2.5 × 10{sup 11} cm{sup −3} has been measured in the extraction region of ROBIN. For negative hydrogen ion beam extraction in second phase operation, extraction system has been assembled and installed with ion source on the vacuum vessel. The source shall be first operated in volume mode for negative ion beam extraction. The commissioning of the source with high voltage power supply has been initiated.

  18. Characterization of Hemagglutinin Negative Botulinum Progenitor Toxins

    Directory of Open Access Journals (Sweden)

    Suzanne R. Kalb

    2017-06-01

    Full Text Available Botulism is a disease involving intoxication with botulinum neurotoxins (BoNTs, toxic proteins produced by Clostridium botulinum and other clostridia. The 150 kDa neurotoxin is produced in conjunction with other proteins to form the botulinum progenitor toxin complex (PTC, alternating in size from 300 kDa to 500 kDa. These progenitor complexes can be classified into hemagglutinin positive or hemagglutinin negative, depending on the ability of some of the neurotoxin-associated proteins (NAPs to cause hemagglutination. The hemagglutinin positive progenitor toxin complex consists of BoNT, nontoxic non-hemagglutinin (NTNH, and three hemagglutinin proteins; HA-70, HA-33, and HA-17. Hemagglutinin negative progenitor toxin complexes contain BoNT and NTNH as the minimally functional PTC (M-PTC, but not the three hemagglutinin proteins. Interestingly, the genome of hemagglutinin negative progenitor toxin complexes comprises open reading frames (orfs which encode for three proteins, but the existence of these proteins has not yet been extensively demonstrated. In this work, we demonstrate that these three proteins exist and form part of the PTC for hemagglutinin negative complexes. Several hemagglutinin negative strains producing BoNT/A, /E, and /F were found to contain the three open reading frame proteins. Additionally, several BoNT/A-containing bivalent strains were examined, and NAPs from both genes, including the open reading frame proteins, were associated with BoNT/A. The open reading frame encoded proteins are more easily removed from the botulinum complex than the hemagglutinin proteins, but are present in several BoNT/A and /F toxin preparations. These are not easily removed from the BoNT/E complex, however, and are present even in commercially-available purified BoNT/E complex.

  19. Triple-negative breast cancer: new perspectives for targeted therapies

    Directory of Open Access Journals (Sweden)

    Tomao F

    2015-01-01

    Full Text Available Federica Tomao,1 Anselmo Papa,2 Eleonora Zaccarelli,2 Luigi Rossi,2 Davide Caruso,2 Marina Minozzi,2 Patrizia Vici,3 Luigi Frati,4 Silverio Tomao21Department of Gynecology and Obstetrics, “Sapienza” University of Rome, Policlinico “Umberto I”, Rome, 2Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, Oncology Unit, Istituto Chirurgico Ortopedico Traumatologico, Latina, 3Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy; 4Department of Molecular Medicine, “Sapienza” University of Rome, Policlinico “Umberto I”, Rome, ItalyAbstract: Breast cancer is a heterogeneous disease, encompassing a large number of entities showing different morphological features and having clinical behaviors. It has became apparent that this diversity may be justified by distinct patterns of genetic, epigenetic, and transcriptomic aberrations. The identification of gene-expression microarray-based characteristics has led to the identification of at least five breast cancer subgroups: luminal A, luminal B, normal breast-like, human epidermal growth factor receptor 2, and basal-like. Triple-negative breast cancer is a complex disease diagnosed by immunohistochemistry, and it is characterized by malignant cells not expressing estrogen receptors or progesterone receptors at all, and human epidermal growth factor receptor 2. Along with this knowledge, recent data show that triple-negative breast cancer has specific molecular features that could be possible targets for new biological targeted drugs. The aim of this article is to explore the use of new drugs in this particular setting, which is still associated with poor prognosis and high risk of distant recurrence and death.Keywords: basal-like breast cancer, estrogen–progesterone receptors, gene-expression microarray, human epidermal growth factor receptor 2, chemotherapy, target therapy

  20. Seeing ghosts: Negative body evaluation predicts overestimation of negative social feedback

    NARCIS (Netherlands)

    Alleva, J.M.; Lange, W.G.; Jansen, A.T.M.; Martijn, C.

    2014-01-01

    The current study investigated whether negative body evaluation predicts women's overestimation of negative social feedback related to their own body (i.e., covariation bias). Sixty-five female university students completed a computer task where photos of their own body, of a control woman's body,

  1. Locating Sites of Negations and Denegating "Negative Essentializing": Rereading Virginia Woolf's "A Room of One's Own"

    Science.gov (United States)

    Adhikari, Manahari

    2014-01-01

    This essay examines how Virginia Woolf uses writing as a tool to locate sites of negations, such as women's exclusion from places of power and knowledge, and to expose negative essentializing that permeates patriarchal structure in "A Room of One's Own." Whereas scholarship on the book has explored a wide range of issues including sex,…

  2. Sentential Negative Markers as Pro-Forms of Negative Sentences in Modern Mongolian

    Science.gov (United States)

    Dagvasumberel, Enkhjargal

    2015-01-01

    Negation in modern Mongolian was analyzed by scholars namely: Luvsanvandan Sh (1968, 2000), Wonsoo Yu (1991), Mönkh-Amgalan Yu (1998), Purev-Ochir B. (1998, 2001), Byambasan P. (2006), Kunihiko Hasimoto (2008), BatIreedui J.(2009), Ravdan E. (2009), Mönkh-Amgalan Yu & Kan Shin (2014). Sentential negation in modern Mongolian is not sufficiently…

  3. NegAIT: A new parser for medical text simplification using morphological, sentential and double negation.

    Science.gov (United States)

    Mukherjee, Partha; Leroy, Gondy; Kauchak, David; Rajanarayanan, Srinidhi; Romero Diaz, Damian Y; Yuan, Nicole P; Pritchard, T Gail; Colina, Sonia

    2017-05-01

    Many different text features influence text readability and content comprehension. Negation is commonly suggested as one such feature, but few general-purpose tools exist to discover negation and studies of the impact of negation on text readability are rare. In this paper, we introduce a new negation parser (NegAIT) for detecting morphological, sentential, and double negation. We evaluated the parser using a human annotated gold standard containing 500 Wikipedia sentences and achieved 95%, 89% and 67% precision with 100%, 80%, and 67% recall, respectively. We also investigate two applications of this new negation parser. First, we performed a corpus statistics study to demonstrate different negation usage in easy and difficult text. Negation usage was compared in six corpora: patient blogs (4K sentences), Cochrane reviews (91K sentences), PubMed abstracts (20K sentences), clinical trial texts (48K sentences), and English and Simple English Wikipedia articles for different medical topics (60K and 6K sentences). The most difficult text contained the least negation. However, when comparing negation types, difficult texts (i.e., Cochrane, PubMed, English Wikipedia and clinical trials) contained significantly (pstudy to show the importance of negation in distinguishing between easy and difficulty text. Five binary classifiers (Naïve Bayes, SVM, decision tree, logistic regression and linear regression) were trained using only negation information. All classifiers achieved better performance than the majority baseline. The Naïve Bayes' classifier achieved the highest accuracy at 77% (9% higher than the majority baseline). Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Negative cognitive errors and positive illusions for negative divorce events: predictors of children's psychological adjustment.

    Science.gov (United States)

    Mazur, E; Wolchik, S A; Sandler, I N

    1992-12-01

    This study examined the relations among negative cognitive errors regarding hypothetical negative divorce events, positive illusions about those same events, actual divorce events, and psychological adjustment in 38 8- to 12-year-old children whose parents had divorced within the previous 2 years. Children's scores on a scale of negative cognitive errors (catastrophizing, overgeneralizing, and personalizing) correlated significantly with self-reported symptoms of anxiety and self-esteem, and with maternal reports of behavior problems. Children's scores on a scale measuring positive illusions (high self-regard, illusion of personal control, and optimism for the future) correlated significantly with less self-reported aggression. Both appraisal types accounted for variance in some measures of symptomatology beyond that explained by actual events. There was no significant association between children's negative cognitive errors and positive illusions. The implications of these results for theories of negative cognitive errors and of positive illusions, as well as for future research, are discussed.

  5. Negative ion beam programs at JAERI

    Science.gov (United States)

    Ohara, Y.

    1990-08-01

    Three negative ion beam programs for nuclear fusion research are proposed at the Japan Atomic Energy Research Institute (JAERI): a 500 keV, 10 MW deuterium neutral beam injection (NBI) for heating and current drive in the JT-60U tokamak, a 0.5/1 MeV, 50 MW deuterium beam injection for the Fusion Experimental Reactor (FER), and a 2 MeV, 20 mA lithium beam injection for ion temperature measurement in the JT-60U. The 500 keV negative-ion-based NBI system for the JT-60U will be developed in the first step, followed by the development of the reactor relevant 0.5/1 MeV NBI system. This two step development mitigates the risk in developing a MeV class NBI system.

  6. Negative electrodes for lithium cells and batteries

    Energy Technology Data Exchange (ETDEWEB)

    Vaughey, John T.; Fransson, Linda M.; Thackeray, Michael M.

    2005-02-15

    A negative electrode is disclosed for a non-aqueous electrochemical cell. The electrode has an intermetallic compound as its basic structural unit with the formula M.sub.2 M' in which M and M' are selected from two or more metal elements including Si, and the M.sub.2 M' structure is a Cu.sub.2 Sb-type structure. Preferably M is Cu, Mn and/or Li, and M' is Sb. Also disclosed is a non-aqueous electrochemical cell having a negative electrode of the type described, an electrolyte and a positive electrode. A plurality of cells may be arranged to form a battery.

  7. Multipole-bound molecular negative ions

    CERN Document Server

    Abdul-Karim, H; Desfrançois, C

    2002-01-01

    Within the framework of a simple electrostatic model, as compared to recent experimental results, we here discuss the stability of very weakly bound molecular negative ions. In contrast with the case of conventional valence anions, the excess electron is then located in a very diffuse orbital and is mainly bound by electrostatic dipolar, quadrupolar, and polarization forces, at large distances from the neutral molecular core. By fitting a single repulsion parameter of the model to the available experimental data, it is possible to make quantitative predictions of the excess-electron binding energies in these species. Critical values of the dipole moment, quadrupole moment or polarizability required for the observation of stable multipole-bound negative ions are predicted and compared to available experimental data and ab initio calculations. Refs. 26 (author)

  8. Magnetic levitation from negative permeability materials

    Energy Technology Data Exchange (ETDEWEB)

    Coffey, Mark W., E-mail: mcoffey@mines.edu [Department of Physics, Colorado School of Mines, Golden, CO 80401 (United States)

    2012-09-03

    As left-handed materials and metamaterials are becoming more prevalent, we examine the effect of negative permeability upon levitation force. We first consider two half spaces of differing permeability and a point magnetic source, so that the method of images may be employed. We determine that the resulting force may be larger than for conventional magnetic materials. We then illustrate the inclusion of a finite sample thickness. -- Highlights: ► The effect of negative permeability upon levitation force is considered. ► Such an effect could be realized with metamaterials. ► The resulting force may be larger than with conventional materials. ► The analysis is extended to allow for a finite sample thickness. ► Representative numerical values are given.

  9. Strategy to Avoid Negative Perception on Game

    Directory of Open Access Journals (Sweden)

    Yedija Prima Putra

    2014-10-01

    Full Text Available In the beginning, games are made to provide entertainment. But, with the interesting entertainment, some game developers use that just for their own benefit. Moreover, many of them including elements of violence and pornography on their games. That is just only to make more profit for them. Thats why some parents are anxious and have a bad view of games. But, not all of the games have elements of violence and pornography. Some of developers make game which is including educational value. "Crazy Machines 2" is one of many games which has educational value. This is one of the ways to Avoid Negative Perception on Game. Key Word : game, creativity, strategy, avoid negative perception

  10. Negative emotional stimuli enhance vestibular processing.

    Science.gov (United States)

    Preuss, Nora; Ellis, Andrew W; Mast, Fred W

    2015-08-01

    Recent studies have shown that vestibular stimulation can influence affective processes. In the present study, we examined whether emotional information can also modulate vestibular perception. Participants performed a vestibular discrimination task on a motion platform while viewing emotional pictures. Six different picture categories were taken from the International Affective Picture System: mutilation, threat, snakes, neutral objects, sports, and erotic pictures. Using a Bayesian hierarchical approach, we were able to show that vestibular discrimination improved when participants viewed emotionally negative pictures (mutilation, threat, snake) when compared to neutral/positive objects. We conclude that some of the mechanisms involved in the processing of vestibular information are also sensitive to emotional content. Emotional information signals importance and mobilizes the body for action. In case of danger, a successful motor response requires precise vestibular processing. Therefore, negative emotional information improves processing of vestibular information. (c) 2015 APA, all rights reserved).

  11. Negative permittivity in bubble and stripe phases

    Science.gov (United States)

    Friess, B.; Peng, Y.; Rosenow, B.; von Oppen, F.; Umansky, V.; von Klitzing, K.; Smet, J. H.

    2017-11-01

    The physics of itinerant electrons in condensed matter is by and large governed by repulsive Coulomb forces. However, attractive interactions may emerge and prevail in determining the ground state despite the pervasive Coulomb repulsion. A notable example is electron pairing and superconductivity. The interplay of attractive and repulsive interactions may also instigate spontaneous symmetry lowering and clustering of charges in geometric patterns even without net attraction. Both types of attractive interaction triggered physics--pairing and charge ordering--are at play in two-dimensional electron systems exposed to a quantizing magnetic field. The charge ordering has been concluded indirectly from transport behaviour. Here we report the observation of negative permittivity present solely when bubble and stripe phases form. In conjunction with a theoretical model, the negative permittivity provides evidence for the underlying attractive exchange-correlation energy which sufficiently countervails Coulomb repulsion at small distances to enable and mediate charge clustering.

  12. Nociception, pain, negative moods and behavior selection

    Science.gov (United States)

    Baliki, Marwan N.; Apkarian, A. Vania

    2015-01-01

    Recent neuroimaging studies suggest that the brain adapts with pain, as well as imparts risk for developing chronic pain. Within this context we revisit the concepts for nociception, acute and chronic pain, and negative moods relative to behavior selection. We redefine nociception as the mechanism protecting the organism from injury; while acute pain as failure of avoidant behavior; and a mesolimbic threshold process that gates the transformation of nociceptive activity to conscious pain. Adaptations in this threshold process are envisioned to be critical for development of chronic pain. We deconstruct chronic pain into four distinct phases, each with specific mechanisms; and outline current state of knowledge regarding these mechanisms: The limbic brain imparting risk, while mesolimbic learning processes reorganizing the neocortex into a chronic pain state. Moreover, pain and negative moods are envisioned as a continuum of aversive behavioral learning, which enhance survival by protecting against threats. PMID:26247858

  13. Structures with negative index of refraction

    Science.gov (United States)

    Soukoulis, Costas M [Ames, IA; Zhou, Jiangfeng [Ames, IA; Koschny, Thomas [Ames, IA; Zhang, Lei [Ames, IA; Tuttle, Gary [Ames, IA

    2011-11-08

    The invention provides simplified negative index materials (NIMs) using wire-pair structures, 4-gap single ring split-ring resonator (SRR), fishnet structures and overleaf capacitor SRR. In the wire-pair arrangement, a pair of short parallel wires and continuous wires are used. In the 4-gap single-ring SRR, the SRRs are centered on the faces of a cubic unit cell combined with a continuous wire type resonator. Combining both elements creates a frequency band where the metamaterial is transparent with simultaneously negative .di-elect cons. and .mu.. In the fishnet structure, a metallic mesh on both sides of the dielectric spacer is used. The overleaf capacitor SRR changes the gap capacities to small plate capacitors by making the sections of the SRR ring overlap at the gaps separated by a thin dielectric film. This technique is applicable to conventional SRR gaps but it best deploys for the 4-gap single-ring structures.

  14. Ghost plasmon and negative dielectric function

    Science.gov (United States)

    Takayanagi, Kazuo; Lipparini, Enrico

    1997-08-01

    We show explicitly that a negative value of the static dielectric function necessarily means the existence of what might be called a ``ghost plasmon,'' a pole of the screened response χsc(q,ω) on the imaginary axis of ω. The ghost plasmon is a collective state exhausting most of the conductivity sum rule. This is demonstrated for a two-dimensional electron gas with a microscopic calculation.

  15. Features of triple-negative breast cancer

    OpenAIRE

    Plasilova, Magdalena L.; Hayse, Brandon; Killelea, Brigid K.; Horowitz, Nina R; Chagpar, Anees B.; Donald R. Lannin

    2016-01-01

    Abstract The aim of this study was to determine the features of triple-negative breast cancer (TNBC) using a large national database. TNBC is known to be an aggressive subtype, but national epidemiologic data are sparse. All patients with invasive breast cancer and known molecular subtype diagnosed in 2010 to 2011 were identified from the National Cancer Data Base (NCDB). Patients with and without TNBC were compared with respect to their sociodemographic and clinicopathologic features. TNBC w...

  16. Adjuvant Therapy of Triple Negative Breast Cancer

    OpenAIRE

    Perez, Edith A.; Moreno-Aspitia, Alvaro; Thompson, E. Aubrey; Andorfer, Cathy A

    2010-01-01

    Patients with the triple negative subtype of breast cancer have an overall poor outcome, with earlier relapses, distinct patterns of metastases, and lack of specific targets for treatment selection. Classification of these tumors has begun to be modified by inclusion of immunohistochemistry for various markers, and gene profiling, to further characterize this subtype of breast cancer, may aid in the identification of new targeted therapies. Anthracyclines and taxanes remain the standard of ca...

  17. Multiband Negative Permittivity Metamaterials and Absorbers

    Directory of Open Access Journals (Sweden)

    Yiran Tian

    2013-01-01

    Full Text Available Design and characteristics of multiband negative permittivity metamaterial and its absorber configuration are presented in this paper. The proposed multiband metamaterial is composed of a novel multibranch resonator which can possess four electric resonance frequencies. It is shown that, by controlling the length of the main branches of such resonator, the resonant frequencies and corresponding absorbing bands of metamaterial absorber can be shifted in a large frequency band.

  18. Enforced Sparse Non-Negative Matrix Factorization

    Science.gov (United States)

    2016-01-23

    mixture of topics constitutes a document. Other common methods for topic modeling include the following: latent semantic analysis (LSA) [1...probabilistic latent semantic analysis (PLSA) [2], and term frequency- inverse document frequency (TF-IDF) [3] analysis. More recently, non-negative matrix...3, pp. 993–1022, 2003. [2] T. Hofmann, “Probabilistic latent semantic indexing,” in Proceedings of the 22nd Annual International ACM SIGIR

  19. Uniform Refraction in Negative Refractive Index Materials

    CERN Document Server

    Gutierrez, Cristian E

    2015-01-01

    We study the problem of constructing an optical surface separating two homogeneous, isotropic media, one of which has a negative refractive index. In doing so, we develop a vector form of Snell's law, which is used to study surfaces possessing a certain uniform refraction property, both in the near and far field cases. In the near field problem, unlike the case when both materials have positive refractive index, we show that the resulting surfaces can be neither convex nor concave.

  20. Anisotropic and Negative Acoustic Index Metamaterials

    OpenAIRE

    Fok, Lee Ren

    2010-01-01

    Microstructured materials are used in material science and engineering to attain desired material properties. Acoustic metamaterials are a rapidly growing area in this field of engineered materials that use deep subwavelength microstructures to attain exotic acoustic properties unavailable in nature. These properties, such as negative acoustic index, allow unprecedented capabilities such as sub-diffraction limit resolution, which have the potential to greatly improve existing technologies l...

  1. ANCA-negative Churg-Strauss Syndrome

    Directory of Open Access Journals (Sweden)

    Syed Jamil Abdal

    2016-08-01

    Full Text Available A rare and a disease of unknown etiology, Churg-Strauss syndrome (CSS is a granulomatous necrotizing small vessel vasculitis characterized by the presence of asthma, sinusitis, and hypereosinophilia, which is initially described by Churg and Strauss in 1951. Because of its clinical and pathological features that overlap with those of the other anti-neutrophil antibody (ANCA-associated systemic vasculitides (AASVs and now the disease is classified as AASVs. The ANCA status may dictate the clinical phenotype. ANCA-positive patients are significantly more likely to have disease manifesta­tions associated with small-vessel vasculitis, including oecrotising glomemlonephritis, mononeuritis and purpura, whereas ANCA-negative cases predominantly likely to have cardiac and lung involvement. The objective of this case report is to point out the possibility of vasculitic rash in ANCA-negative CSS in a 35-year-old man and the disease rarely occurs in Bangladeshi population. We analyze the history, clinical examinations and relevant investigations related to the patient to establish the diagnosis in our department. The clinical scenario and biopsy help us to attain the diagnosis. But due to unavailability of patients' cohort we have limitations of comparison of ANCA status in Bangladeshi populations. Though ANCA-positive and ANCA-negative CSS differ phenotypically, primary therapy for both the conditions is systemic glucocorticoids. Additional immunosuppressive agents like cyclophosphamide, mycophenolate mofetil, azathioprine, rituxin1ab are occasionally added in patients with more advanced or refractory disease.

  2. LIFE EVENTS AND NEGATIVE RELIGIOUS COPING

    Directory of Open Access Journals (Sweden)

    sema eryücel

    2013-07-01

    Full Text Available ABSTRACT Recently, insufficiency of secular coping methods has drawn the attention of researchers towards religious coping methods. While the parts about theory and model cover an important place in the literature, experimental studies are rapidly going on. Although religious coping was initially interpreted as positive, experimental studies reveal that it also has negative forms. The purpose of this study, in which qualitative research methods were used, is to define the components of religious coping. Semi structured interview was used among 42 participants, 9 war veterans from Association of Turkish Disabled War Veterans, Martyrs, their Widows and Orphans Ankara Branch, and 9 relatives of martyrs from the Association of Martyrs’ Families Ankara Branch, totaling 60 volunteer participants between the ages 25 and 65 with snowball sampling method. It was discovered that 29 of the participants used negative religious coping and the participants who only used negative religious coping were studied in this research. Upon recording the interviews with the aid of a recorder, the researched typed the script of the interviews. The qualitative analysis of the collected data was done in MAXODA 11 computer program.

  3. Negative Results in European Psychology Journals

    Directory of Open Access Journals (Sweden)

    Martin Rachev Vasilev

    2013-11-01

    Full Text Available Psychologists have long speculated that the research literature is largely dominated by positive findings, but yet there is little data to justify these speculations. The present study investigates the extent to which negative findings exist in the literature by reviewing articles published in five European psychology journals. While no temporal change was observed, the results indicate that almost all (95.4% articles published in 2001, 2006 and 2011 found support for at least one tested hypothesis. Moreover, a sizable number (73% of papers found support for all tested hypotheses. It is argued that the lack of negative findings can have a detrimental effect on the ability to systemize scientific knowledge, the way science is practiced, and the rate of replications in psychology. Publishing positive findings may be very important for making progress in our field, but negative findings are also crucial for maintaining its scientific integrity. When we base our conclusions on results that support our predictions and ignore data to the contrary, we run the risk of creating a biased view of reality that gives us little confidence in the validity and applicability of our findings.

  4. Negative Knudsen force on heated microbeams

    KAUST Repository

    Zhu, Taishan

    2011-11-18

    Knudsen force acting on a heated microbeam adjacent to a cold substrate in a rarefied gas is a mechanical force created by unbalanced thermal gradients. The measured force has its direction pointing towards the side with a lower thermal gradient and its magnitude vanishes in both continuum and free-molecule limits. In our previous study, negative Knudsen forces were discovered at the high Knudsen regime before diminishing in the free-molecule limit. Such a phenomenon was, however, neither observed in experiment [A. Passian et al., Phys. Rev. Lett. 90, 124503 (2003)], nor captured in the latest numerical study [J. Nabeth et al., Phys. Rev. E 83, 066306 (2011)]. In this paper, the existence of such a negative Knudsen force is further confirmed using both numerical simulation and theoretical analysis. The asymptotic order of the Knudsen force near the collisionless limit is analyzed and the analytical expression of its leading term is provided, from which approaches for the enhancement of negative Knudsen forces are proposed. The discovered phenomenon could find its applications in novel mechanisms for pressure sensing and actuation.

  5. Negative Halogen Ions for Fusion Applications

    Energy Technology Data Exchange (ETDEWEB)

    Grisham, L.R.; Kwan, J.W.; Hahto, S.K.; Hahto, S.T.; Leung, K.N.; Westenskow, G.

    2006-01-01

    Over the past quarter century, advances in hydrogen negative ion sources have extended the usable range of hydrogen isotope neutral beams to energies suitable for large magnetically confined fusion devices. Recently, drawing upon this experience, negative halogen ions have been proposed as an alternative to positive ions for heavy ion fusion drivers in inertial confinement fusion, because electron accumulation would be prevented in negative ion beams, and if desired, the beams could be photo-detached to neutrals. This paper reports the results of an experiment comparing the current density and beam emittance of Cl+ and Cl- extracted from substantially ion-ion plasmas with that of Ar+ extracted from an ordinary electron-ion plasma, all using the same source, extractor, and emittance scanner. At similar discharge conditions, the Cl- current was typically 85 – 90% of the positive chlorine current, with an e-/ Cl- ratio as low as seven without grid magnets. The Cl- was as much as 76% of the Ar+ current from a discharge with the same RF drive. The minimum normalized beam emittance and inferred ion temperatures of Cl+, Cl-, and Ar+ were all similar, so the current density and optical quality of Cl- appear as suitable for heavy ion fusion driver applications as a positive noble gas ion of similar mass. Since F, I, and Br should all behave similarly in an ion source, they should also be suitable as driver beams.

  6. Negative Mood Increases Selective Attention to Negatively Valenced Body Parts in Female Adolescents with Anorexia Nervosa.

    Science.gov (United States)

    Svaldi, Jennifer; Bender, Caroline; Caffier, Detlef; Ivanova, Viliana; Mies, Nina; Fleischhaker, Christian; Tuschen-Caffier, Brunna

    2016-01-01

    Previous research has yielded evidence of increased attentional processing of negatively valenced body parts in women with anorexia nervosa (AN), especially for those with high depressive symptomatology. The present study extended previous research by implementing an experimental mood manipulation. In a within-subjects design, female adolescents with AN (n = 12) and an age matched female control group (CG; n = 12) were given a negative and a positive mood induction at a one-week interval. After each mood induction, participants underwent a 3-min mirror exposure, while their eye movements were recorded. After the positive mood induction, both AN and CG participants displayed longer and more frequent gazes towards their self-defined most ugly relative to their self-defined most beautiful body part. However, after the negative mood induction, only females with AN were characterized by increased attention to their most ugly compared to their most beautiful body part, while CG participants' attention distribution was balanced. Furthermore, in the negative (but not in the positive) mood induction condition gaze frequency and duration towards the most ugly body part was significantly stronger in the AN group relative to the CG. The results emphasize the role of negative mood in the maintenance of pathological information processing of the self-body. This increased body-related negativity-bias during negative mood may lead to the persistence and aggravation of AN patients' body image disturbance.

  7. Gram-negative bacteraemia in haemodialysis.

    Science.gov (United States)

    Murray, Eleanor C; Marek, Aleksandra; Thomson, Peter C; Coia, John E

    2015-07-01

    Patients on renal replacement therapy experience higher rates of morbidity and mortality, infection being the second commonest cause of death. In our haemodialysis population, we identify the pathogens, sensitivity patterns, sources of infection and outcomes of Gram-negative bacteraemia. Data from the NHS Greater Glasgow & Clyde and NHS Forth Valley haemodialysis population were collected July 2011 to April 2014 through an interrogation of the renal unit electronic patient record, and confirmed by an independent search of the Microbiology database. Over 544 377 haemodialysis days, 84 patients experienced 95 Gram-negative bacteraemia events, a rate of 0.175 events per 1000 haemodialysis days, which varied with dialysis modality: non-tunnelled central venous catheters 4.77, arteriovenous grafts 0.24, tunnelled central venous catheters 0.21, and arteriovenous fistulae 0.11 per 1000 haemodialysis days. The commonest sources of bacteraemia were central venous catheters (CVCs) (16.8%, n = 16), infected ulcers (14.7%, n = 14), urinary (10.5%, n = 10), biliary (9.5%, n = 9) and intra-abdominal (9.5%, n = 9).The principal organisms were Escherichia coli (49.5%, n = 47), Enterobacter spp. (13.1%, n = 13), Klebsiella spp. (11.1%, n = 11), Proteus mirabilis (6.1%, n = 6) and Pseudomonas aeruginosa (5.1%, n = 5). Of the Enterobacteriaceae (n = 84), 88% were sensitive to gentamicin, 81% to ciprofloxacin, 91% to piperacillin-tazobactam and 100% were sensitive to meropenem.Three-month case mortality was 25.3% (n = 24). Ten patients (11.9%) had more than one Gram-negative bacteraemia; of these, nine patients (90.0%) were the same causative organism, predominantly E. coli. CVCs and diabetic foot ulcers remain significant risk factors for Gram-negative bacteraemia, highlighting the importance of vascular access planning. Despite good levels of antibiotic sensitivity, the early mortality following Gram-negative bacteraemia remains high, supporting aggressive treatment of such

  8. Virulence plasmid of Rhodococcus equi contains inducible gene family encoding secreted proteins.

    Science.gov (United States)

    Byrne, B A; Prescott, J F; Palmer, G H; Takai, S; Nicholson, V M; Alperin, D C; Hines, S A

    2001-02-01

    Rhodococcus equi causes severe pyogranulomatous pneumonia in foals. This facultative intracellular pathogen produces similar lesions in immunocompromised humans, particularly in AIDS patients. Virulent strains of R. equi bear a large plasmid that is required for intracellular survival within macrophages and for virulence in foals and mice. Only two plasmid-encoded proteins have been described previously; a 15- to 17-kDa surface protein designated virulence-associated protein A (VapA) and an antigenically related 20-kDa protein (herein designated VapB). These two proteins are not expressed by the same R. equi isolate. We describe here the substantial similarity between VapA and VapB. Moreover, we identify three additional genes carried on the virulence plasmid, vapC, -D, and -E, that are tandemly arranged downstream of vapA. These new genes are members of a gene family and encode proteins that are approximately 50% homologous to VapA, VapB, and each other. vapC, -D, and -E are found only in R. equi strains that express VapA and are highly conserved in VapA-positive isolates from both horses and humans. VapC, -D, and -E are secreted proteins coordinately regulated by temperature with VapA; the proteins are expressed when R. equi is cultured at 37 degrees C but not at 30 degrees C, a finding that is compatible with a role in virulence. As secreted proteins, VapC, -D, and -E may represent targets for the prevention of rhodococcal pneumonia. An immunologic study using VapA-specific antibodies and recombinant Vap proteins revealed no evidence of cross-reactivity despite extensive sequence similarity over the carboxy terminus of all four proteins.

  9. Dependency Parser-based Negation Detection in Clinical Narratives.

    Science.gov (United States)

    Sohn, Sunghwan; Wu, Stephen; Chute, Christopher G

    2012-01-01

    Negation of clinical named entities is common in clinical documents and is a crucial factor to accurately compile patients' clinical conditions and to further support complex phenotype detection. In 2009, Mayo Clinic released the clinical Text Analysis and Knowledge Extraction System (cTAKES), which includes a negation annotator that identifies negation status of a named entity by searching for negation words within a fixed word distance. However, this negation strategy is not sophisticated enough to correctly identify complicated patterns of negation. This paper aims to investigate whether the dependency structure from the cTAKES dependency parser can improve the negation detection performance. Manually compiled negation rules, derived from dependency paths were tested. Dependency negation rules do not limit the negation scope to word distance; instead, they are based on syntactic context. We found that using a dependency-based negation proved a superior alternative to the current cTAKES negation annotator.

  10. Improving Universal Suicide Prevention Screening in Primary Care by Reducing False Negatives

    Science.gov (United States)

    2016-09-01

    6 5.4. Significant changes in use or care of human subjects, vertebrate animals, biohazards...changes in use or care of human subjects, vertebrate animals, biohazards, and/or select agents Nothing to Report. 6. Products: 6.1. Publications...AWARD NUMBER: W81XWH-14-1-0272 TITLE: Improving universal suicide prevention screening in primary care by reducing false negatives PRINCIPAL

  11. Social rejection magnifies impulsive behavior among individuals with greater negative urgency: An experimental test of urgency theory.

    Science.gov (United States)

    Chester, David S; Lynam, Donald R; Milich, Richard; DeWall, C Nathan

    2017-07-01

    Impulsivity is a multifaceted trait with substantial implications for human well-being. One facet of impulsivity is negative urgency, the tendency to act impulsively in response to negative affect. Correlational evidence suggests that negative affect magnifies impulsive behavior among individuals with greater negative urgency, yet causal evidence for this core pillar of urgency theory is lacking. To fill this gap in the literature, participants (N = 363) were randomly assigned to experience social rejection (a situation shown to induce negative affect) or acceptance. Participants then reported their subjective negative affect, completed a behavioral measure of impulsivity, and reported their negative urgency. Among individuals with relatively high and average negative urgency, social rejection increased their impulsive behavior through greater experiences of negative affect. These indirect effects were not observed among individuals relatively low in negative urgency. These findings suggest that negative urgency exists at the nexus of urgent dispositions and situations that elicit negative affect, which offers novel support for urgency theory. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. Pregnancy presenting as hyperthyroidism with negative urine pregnancy test.

    Science.gov (United States)

    Jindal, Rita; Deepak, Desh; Ghosh, Gopal Chandra; Gupta, Mamta

    2014-05-20

    A 22-year-old lactating mother presented with symptoms of uneasiness, palpitation, tachycardia and exophthalmos. She had an abdominal lump suggestive of 26 weeks uterine size but her urine pregnancy test was negative. Her thyroid profile was suggestive of hyperthyroidism. Gynaecological and ultrasonographic findings revealed a hydatidiform mole. She had a low β-human chorionic gonadotropin level that surprisingly increased after suction and evacuation. The paradoxical findings that appeared as erroneous laboratory results could be explained by the 'high-dose hook effect' after a review of literature. One week after the evacuation, the patient's thyroid profile and symptoms resolved completely without any treatment for hyperthyroidism. 2014 BMJ Publishing Group Ltd.

  13. Positive and negative impact of increased tertiary attainment

    Directory of Open Access Journals (Sweden)

    Alena Bušíková

    2013-04-01

    Full Text Available The theory of human capital clearly states that the investments into the education bring many benefits and are worth the cost. The OECD Education at a Glance analysis provides support for both public and private investing in tertiary education as the net present value is positive for all observed countries. Considering the benefits of education, a growth in tertiary education should be viewed very positively. In this context, the European Strategy Europe 2020 set up one of its main goals for EU27 countries as follows: to increase the educated population so that it reaches 40% (tertiary educated people aged 30-34. This article, on an example of Slovakia, provides an analysis of both positive and negative impact of increased tertiary attainment.

  14. Hospital nurses? attitudes, negative perceptions, and negative acts regarding workplace bullying

    OpenAIRE

    Ma, Shu-Ching; Wang, Hsiu-Hung; Chien, Tsair-Wei

    2017-01-01

    Background Workplace bullying is a prevalent problem in today?s work places that has adverse effects on both bullying victims and organizations. To investigate the predictors of workplace bullying is an important task to prevent bullying victims of nurses in hospitals. Objective This study aims to explore the relationships among nurses? attitudes, negative perceptions, and negative acts regarding workplace bullying under the framework of the theory of planned behavior (TPB). Methods A total o...

  15. Realistic artificial DNA sequences as negative controls for computational genomics

    Science.gov (United States)

    Caballero, Juan; Smit, Arian F. A.; Hood, Leroy; Glusman, Gustavo

    2014-01-01

    A common practice in computational genomic analysis is to use a set of ‘background’ sequences as negative controls for evaluating the false-positive rates of prediction tools, such as gene identification programs and algorithms for detection of cis-regulatory elements. Such ‘background’ sequences are generally taken from regions of the genome presumed to be intergenic, or generated synthetically by ‘shuffling’ real sequences. This last method can lead to underestimation of false-positive rates. We developed a new method for generating artificial sequences that are modeled after real intergenic sequences in terms of composition, complexity and interspersed repeat content. These artificial sequences can serve as an inexhaustible source of high-quality negative controls. We used artificial sequences to evaluate the false-positive rates of a set of programs for detecting interspersed repeats, ab initio prediction of coding genes, transcribed regions and non-coding genes. We found that RepeatMasker is more accurate than PClouds, Augustus has the lowest false-positive rate of the coding gene prediction programs tested, and Infernal has a low false-positive rate for non-coding gene detection. A web service, source code and the models for human and many other species are freely available at http://repeatmasker.org/garlic/. PMID:24803667

  16. Realistic artificial DNA sequences as negative controls for computational genomics.

    Science.gov (United States)

    Caballero, Juan; Smit, Arian F A; Hood, Leroy; Glusman, Gustavo

    2014-07-01

    A common practice in computational genomic analysis is to use a set of 'background' sequences as negative controls for evaluating the false-positive rates of prediction tools, such as gene identification programs and algorithms for detection of cis-regulatory elements. Such 'background' sequences are generally taken from regions of the genome presumed to be intergenic, or generated synthetically by 'shuffling' real sequences. This last method can lead to underestimation of false-positive rates. We developed a new method for generating artificial sequences that are modeled after real intergenic sequences in terms of composition, complexity and interspersed repeat content. These artificial sequences can serve as an inexhaustible source of high-quality negative controls. We used artificial sequences to evaluate the false-positive rates of a set of programs for detecting interspersed repeats, ab initio prediction of coding genes, transcribed regions and non-coding genes. We found that RepeatMasker is more accurate than PClouds, Augustus has the lowest false-positive rate of the coding gene prediction programs tested, and Infernal has a low false-positive rate for non-coding gene detection. A web service, source code and the models for human and many other species are freely available at http://repeatmasker.org/garlic/. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. The RNA synthesis machinery of negative-stranded RNA viruses

    Energy Technology Data Exchange (ETDEWEB)

    Ortín, Juan, E-mail: jortin@cnb.csic.es [Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CSIC) and CIBER de Enfermedades Respiratorias (ISCIII), Madrid (Spain); Martín-Benito, Jaime, E-mail: jmartinb@cnb.csic.es [Department of Macromolecular Structures, Centro Nacional de Biotecnología (CSIC), Madrid (Spain)

    2015-05-15

    The group of Negative-Stranded RNA Viruses (NSVs) includes many human pathogens, like the influenza, measles, mumps, respiratory syncytial or Ebola viruses, which produce frequent epidemics of disease and occasional, high mortality outbreaks by transmission from animal reservoirs. The genome of NSVs consists of one to several single-stranded, negative-polarity RNA molecules that are always assembled into mega Dalton-sized complexes by association to many nucleoprotein monomers. These RNA-protein complexes or ribonucleoproteins function as templates for transcription and replication by action of the viral RNA polymerase and accessory proteins. Here we review our knowledge on these large RNA-synthesis machines, including the structure of their components, the interactions among them and their enzymatic activities, and we discuss models showing how they perform the virus transcription and replication programmes. - Highlights: • Overall organisation of NSV RNA synthesis machines. • Structure and function of the ribonucleoprotein components: Atomic structure of the RNA polymerase complex. • Commonalities and differences between segmented- and non-segmented NSVs. • Transcription versus replication programmes.

  18. Negative density-distribution relationship in butterflies

    Directory of Open Access Journals (Sweden)

    Kotiaho Janne S

    2005-03-01

    Full Text Available Abstract Background Because "laws of nature" do not exist in ecology, much of the foundations of community ecology rely on broad statistical generalisations. One of the strongest generalisations is the positive relationship between density and distribution within a given taxonomic assemblage; that is, locally abundant species are more widespread than locally sparse species. Several mechanisms have been proposed to create this positive relationship, and the testing of these mechanisms is attracting increasing attention. Results We report a strong, but counterintuitive, negative relationship between density and distribution in the butterfly fauna of Finland. With an exceptionally comprehensive data set (data includes all 95 resident species in Finland and over 1.5 million individuals, we have been able to submit several of the mechanisms to powerful direct empirical testing. Without exception, we failed to find evidence for the proposed mechanisms creating a positive density-distribution relationship. On the contrary, we found that many of the mechanisms are equally able to generate a negative relationship. Conclusion We suggest that one important determinant of density-distribution relationships is the geographical location of the study: on the edge of a distribution range, suitable habitat patches are likely to be more isolated than in the core of the range. In such a situation, only the largest and best quality patches are likely to be occupied, and these by definition can support a relatively dense population leading to a negative density-distribution relationship. Finally, we conclude that generalizations about the positive density-distribution relationship should be made more cautiously.

  19. BNL negative ion based neutral beam development

    Energy Technology Data Exchange (ETDEWEB)

    Alessi, J.G.; Hershcovitch, A.; Kovarik, V.; Larson, R.A.; McKenzie-Wilson, R.; Prelec, K.; Sluyters, T.

    1981-01-01

    The BNL Neutral Beam Development Group has as its objective the development of neutral beam systems, using negative ion sources with high current density. In this past year we have made the transition from pulsed high current negative ion sources to sources designed to operate steady state. We are presently testing two dc sources, a magnetron source and a modified magnetron with plasma injection from a hollow cathode discharge (HCD). Both sources have operated with steady state discharges; to date 0.11A of H/sup -/ has been extracted from the standard magnetron while about 1A of H/sup -/ has been produced on a surface, but not extracted, in the HCD system. Present plans are to transport the beam from a 2A magnetron around a bending magnet, followed by dc acceleration of the beam to 200 keV. These units would be stacked to obtain higher currents. The HCD source is expected to operate at much lower pressures (10/sup -4/ - 10/sup -3/ Torr), and therefore close coupled acceleration of the beam to 200 keV is envisioned. This makes the source module considerably more compact. The MEQA-LAC, dc acceleration with periodic electrostatic quadrupole focusing, and the RFQ are being considered as ways to accelerate negative ion beams to energies above 200 keV. In the neutral beam line a novel plasma neutralizer is being considered which uses HCD's to feed a plasma into a solenoidal magnetic field. This should result in a high plasma density (10/sup 13/ - 10/sup 14/ cm/sup -3/) with a low background gas pressure.

  20. Negative pressure therapy: theory and practice.

    Science.gov (United States)

    Schintler, M V

    2012-02-01

    Negative pressure (wound) therapy, synonymous with topical negative pressure or vacuum therapy mainly cited as branded VAC® (vacuum-assisted closure) therapy, is a mode of therapy used to encourage wound healing. It is used both as primary treatment of chronic and complex wounds and as an adjunct for temporary closure and wound bed preparation preceding surgical procedures such as skin grafts and flap surgery. The device has come into wide and successful use, although the physiological basis of its effect is not yet fully understood, and with a delay, increasingly evidence-based data become available. A meta-analysis was made of peer-reviewed publications (PubMed-Medline) chosen on the basis of inclusion of the terms randomized clinical trial, vacuum-assisted closure, and topical negative pressure. Scientific data were evaluated from experimental animal studies, randomized clinical trials, observations of clinical applications, and case reports on all known effects of VAC therapy. Systematic analysis of the data shows efficacy concerning induction of wound healing mechanisms, especially in the early stage. Increased perfusion can be considered proven. Data analysis shows positive efficacy for treatment of infection. Although this therapy appears effective and its superiority to conventional techniques has been demonstrated, there are still some critical votes concerning efficacy. Because its mechanisms of action remain unclear, and because there is still some gap between evidence-based data and the excellent clinical results, further prospective, randomized, blinded studies are needed. Even so, we conclude that vacuum therapy, used when indicated and especially by experienced surgeons, is an excellent tool to support wound healing. Copyright © 2012 John Wiley & Sons, Ltd.

  1. Vitamin a is a negative regulator of osteoblast mineralization.

    Directory of Open Access Journals (Sweden)

    Thomas Lind

    Full Text Available An excessive intake of vitamin A has been associated with an increased risk of fractures in humans. In animals, a high vitamin A intake leads to a reduction of long bone diameter and spontaneous fractures. Studies in rodents indicate that the bone thinning is due to increased periosteal bone resorption and reduced radial growth. Whether the latter is a consequence of direct effects on bone or indirect effects on appetite and general growth is unknown. In this study we therefore used pair-feeding and dynamic histomorphometry to investigate the direct effect of a high intake of vitamin A on bone formation in rats. Although there were no differences in body weight or femur length compared to controls, there was an approximately halved bone formation and mineral apposition rate at the femur diaphysis of rats fed vitamin A. To try to clarify the mechanism(s behind this reduction, we treated primary human osteoblasts and a murine preosteoblastic cell line (MC3T3-E1 with the active metabolite of vitamin A; retinoic acid (RA, a retinoic acid receptor (RAR antagonist (AGN194310, and a Cyp26 inhibitor (R115866 which blocks endogenous RA catabolism. We found that RA, via RARs, suppressed in vitro mineralization. This was independent of a negative effect on osteoblast proliferation. Alkaline phosphatase and bone gamma carboxyglutamate protein (Bglap, Osteocalcin were drastically reduced in RA treated cells and RA also reduced the protein levels of Runx2 and Osterix, key transcription factors for progression to a mature osteoblast. Normal osteoblast differentiation involved up regulation of Cyp26b1, the major enzyme responsible for RA degradation, suggesting that a drop in RA signaling is required for osteogenesis analogous to what has been found for chondrogenesis. In addition, RA decreased Phex, an osteoblast/osteocyte protein necessary for mineralization. Taken together, our data indicate that vitamin A is a negative regulator of osteoblast mineralization.

  2. Ghost plasmon and negative dielectric function

    Energy Technology Data Exchange (ETDEWEB)

    Takayanagi, K. [Department of Physics, Sophia University, 7-1 Kioi-cho, Chiyoda-ku, Tokyo 102 (Japan); Lipparini, E. [Dipartimento di Fisica, Universita degli Studi di Trento and Gruppo Collegato, Istituto Nazionale di Fisica Nucleare, Trento, I-38050 Povo Trento (Italy)

    1997-08-01

    We show explicitly that a negative value of the static dielectric function necessarily means the existence of what might be called a {open_quotes}ghost plasmon,{close_quotes} a pole of the screened response {chi}{sup sc}(q,{omega}) on the imaginary axis of {omega}. The ghost plasmon is a collective state exhausting most of the conductivity sum rule. This is demonstrated for a two-dimensional electron gas with a microscopic calculation. {copyright} {ital 1997} {ital The American Physical Society}

  3. Quorum sensing in gram-negative bacteria

    DEFF Research Database (Denmark)

    Wu, H.; Song, Z.J.; Høiby, N.

    2004-01-01

    Bacteria can communicate with each other by means of signal molecules to coordinate the behavior of the entire community, and the mechanism is referred to as quorum sensing (QS). Signal systems enable bacteria to sense the size of their densities by monitoring the concentration of the signal...... molecules. Among Gram-negative bacteria N-acyl-L-homoserine lactone (acyl-HSL)-dependent quorum sensing systems are particularly widespread. These systems are used to coordinate expression of phenotypes that are fundamental to the interaction of bacteria with each other and with their environment...

  4. Single-resonator double-negative metamaterial

    Science.gov (United States)

    Warne, Larry K.; Basilio, Lorena I.; Langston, William L.; Johnson, William A.; Ihlefeld, Jon; Ginn, III, James C.; Clem, Paul G.; Sinclair, Michael B.

    2016-06-21

    Resonances can be tuned in dielectric resonators in order to construct single-resonator, negative-index metamaterials. For example, high-contrast inclusions in the form of metallic dipoles can be used to shift the first electric resonance down (in frequency) to the first magnetic resonance, or alternatively, air splits can be used to shift the first magnetic resonance up (in frequency) near the first electric resonance. Degenerate dielectric designs become especially useful in infrared- or visible-frequency applications where the resonator sizes associated with the lack of high-permittivity materials can become of sufficient size to enable propagation of higher-order lattice modes in the resulting medium.

  5. Trees and Fields and Negative Polarity

    DEFF Research Database (Denmark)

    Vikner, Sten

    2011-01-01

    The paper takes as its point of departure a comparison between two kinds of approaches to clause structure, namely tree analyses like the generative analysis and field analyses like the sætningsskema analysis of Danish of Diderichsen (1946) and many others (or like the topologische Modell analysi...... to accounting for negative polarity items in English, Danish and German, both the more straightforward aspects and the more complex ones, e.g. the so-called NPI-verbs as well as the interaction between NPI-elements and because-clauses...

  6. Culture Negative Infective Endocarditits: a Changing Paradigm

    LENUS (Irish Health Repository)

    Daly, A

    2016-05-01

    Traditionally, the modified Duke\\'s criteria, based primarily on positive blood cultures, is used to diagnose Infective Endocarditis (IE). However, reports demonstrate that 31% of cases are diagnosed as Culture Negative Infective Endocarditis (CNIE)1. Consequently, empiric broad-spectrum antibiotics are prescribed to cover unidentified organisms and, as a result, antibiotic therapy may be compromised. Molecular diagnostic techniques aid with identifying causative organisms in cases of CNIE and we question if the increasing use of such technologies will change the local epidemiology of CNIE. We present the first case of Tropheryma whipplei Infective Endocarditis (TWIE) reported in Ireland.

  7. ATTITUDE STATEMENTS AS POSITIVE AND NEGATIVE REINFORCEMENTS.

    Science.gov (United States)

    GOLIGHTLY, C; BYRNE, D

    1964-11-06

    The finding that attraction is a function of attitude similarity has been interpreted as a special case of the effect of positive and negative reinforcements on attraction. A simple discrimination learning task was employed in which the reinforcements were attitude statements similar and dissimilar to the opinions of the subject. The presentation of similar attitude statements after each correct response and dissimilar attitude statements after each incorrect response significantly changed response probability. The hypothesis that such statements could be used as reinforcers in a learning situation was thus confirmed.

  8. Object habituation in horses: The effect of voluntary vs. negatively reinforced approach to frightening stimuli

    DEFF Research Database (Denmark)

    Christensen, Janne Winther

    2013-01-01

    Reasons for performing the study: The ability of horses to habituate to novel objects influences safety in the horse–human relationship. However, the effectiveness of different habituation techniques has not been investigated in detail. Objectives: 1) To investigate whether horses show increased...... stress responses when negatively reinforced to approach novel objects, compared with horses allowed to voluntarily explore the objects and 2) whether a negatively reinforced approach facilitates object habituation. Methods: Twenty-two 2–3-year-old Danish Warmblood geldings were included. Half...... of the horses (NR group) were negatively reinforced by a familiar human handler to approach a collection of novel objects in a test arena. The other half were individually released in the arena and were free to explore the objects (VOL group). On the next day, the horses were exposed to the objects again...

  9. Doubled strings, negative strings and null waves

    Energy Technology Data Exchange (ETDEWEB)

    Blair, Chris D.A. [Theoretische Natuurkunde, Vrije Universiteit Brussel, and the International Solvay Institutes,Pleinlaan 2, B-1050 Brussels (Belgium)

    2016-11-08

    We revisit the fundamental string (F1) solution in the doubled formalism. We show that the wave-like solution of double field theory (DFT) corresponding to the F1/pp-wave duality pair is more properly a solution of the DFT action coupled to a doubled sigma model action. The doubled string configuration which sources the pp-wave can be thought of as static gauge with the string oriented in a dual direction. We also discuss the DFT solution corresponding to a vibrating string, carrying both winding and momentum. We further show that the solution dual to the F1 in both time and space can be viewed as a “negative string” solution. Negative branes are closely connected to certain exotic string theories which involve unusual signatures for both spacetime and brane worldvolumes. In order to better understand this from the doubled point of view, we construct a variant of DFT suitable for describing theories in which the fundamental string has a Euclidean worldsheet, for which T-dualities appear to change the spacetime signature.

  10. Development of versatile multiaperture negative ion sources

    Science.gov (United States)

    Cavenago, M.; Serianni, G.; Antoni, V.; Bigi, M.; De Muri, M.; Pasqualotto, R.; Recchia, M.; Veltri, P.; Agostinetti, P.; Barbisan, M.; Baseggio, L.; Cervaro, V.; Cazzador, M.; Degli Agostini, F.; Franchin, L.; Kulevoy, T.; Laterza, B.; Mimo, A.; Minarello, A.; Petrenko, S.; Ravarotto, D.; Rossetto, F.; Sattin, M.; Zaniol, B.; Zucchetti, S.

    2015-04-01

    Enhancement of negative ion sources for production of large ion beams is a very active research field nowadays, driven from demand of plasma heating in nuclear fusion devices and accelerator applications. As a versatile test bench, the ion source NIO1 (Negative Ion Optimization 1) is being commissioned by Consorzio RFX and INFN. The nominal beam current of 135 mA at -60 kV is divided into 9 beamlets, with multiaperture extraction electrodes. The plasma is sustained by a 2 MHz radiofrequency power supply, with a standard matching box. A High Voltage Deck (HVD) placed inside the lead shielding surrounding NIO1 contains the radiofrequency generator, the gas control, electronics and power supplies for the ion source. An autonomous closed circuit water cooling system was installed for the whole system, with a branch towards the HVD, using carefully optimized helical tubing. Insulation transformer is installed in a nearby box. Tests of several magnetic configurations can be performed. Status of experiments, measured spectra and plasma luminosity are described. Upgrades of magnetic filter, beam calorimeter and extraction grid and related theoretical issues are reviewed.

  11. Inflation and Growth: Positive or Negative Relationship?

    Science.gov (United States)

    Berument, Hakan; Inamlik, Ali; Olgun, Hasan

    This study has been motivated by two developments. Firstly, by the vast literature on the relationship between inflation and growth which is abundantly endowed with diverse theoretical explanations and contradictory evidence and by the unique experience of the Turkish economy with inflation and growth. A preliminary examination of the Turkish data pointed to a negative relation between inflation and growth. Moreover, there is a unanimous agreement among the students of the Turkish economy that many factors have contributed to inflation in this country. In view of these facts this paper employs a VAR model which will enable us to identify the sources of the shocks and control for external factors. In addition VAR models have a high predictive power and enable the researcher to observe the impulse response functions. The study employs Generalised Impulse Response analysis. In the empirical experiments oil prices, money supply, government spending and taxes have been taken as the most likely determinants of inflation. The study shows that there is a negative relationship between inflation and output growth in Turkey and that the underlying explanatory factor is the real exchange rate. This result is robust.

  12. Nitric oxide negatively regulates mammalian adult neurogenesis

    Science.gov (United States)

    Packer, Michael A.; Stasiv, Yuri; Benraiss, Abdellatif; Chmielnicki, Eva; Grinberg, Alexander; Westphal, Heiner; Goldman, Steven A.; Enikolopov, Grigori

    2003-08-01

    Neural progenitor cells are widespread throughout the adult central nervous system but only give rise to neurons in specific loci. Negative regulators of neurogenesis have therefore been postulated, but none have yet been identified as subserving a significant role in the adult brain. Here we report that nitric oxide (NO) acts as an important negative regulator of cell proliferation in the adult mammalian brain. We used two independent approaches to examine the function of NO in adult neurogenesis. In a pharmacological approach, we suppressed NO production in the rat brain by intraventricular infusion of an NO synthase inhibitor. In a genetic approach, we generated a null mutant neuronal NO synthase knockout mouse line by targeting the exon encoding active center of the enzyme. In both models, the number of new cells generated in neurogenic areas of the adult brain, the olfactory subependyma and the dentate gyrus, was strongly augmented, which indicates that division of neural stem cells in the adult brain is controlled by NO and suggests a strategy for enhancing neurogenesis in the adult central nervous system.

  13. Distance Sensitive Bloom Filters Without False Negatives

    DEFF Research Database (Denmark)

    Goswami, Mayank; Pagh, Rasmus; Silvestri, Francesco

    2017-01-01

    A Bloom filter is a widely used data-structure for representing a set S and answering queries of the form “Is x in S?”. By allowing some false positive answers (saying ‘yes’ when the answer is in fact ‘no’) Bloom filters use space significantly below what is required for storing S. In the distance...... sensitive setting we work with a set S of (Hamming) vectors and seek a data structure that offers a similar trade-off, but answers queries of the form “Is x close to an element of S?” (in Hamming distance). Previous work on distance sensitive Bloom filters have accepted false positive and false negative...... answers. Absence of false negatives is of critical importance in many applications of Bloom filters, so it is natural to ask if this can be also achieved in the distance sensitive setting. Our main contributions are upper and lower bounds (that are tight in several cases) for space usage in the distance...

  14. Will Automated Vehicles Negatively Impact Traffic Flow?

    Directory of Open Access Journals (Sweden)

    S. C. Calvert

    2017-01-01

    Full Text Available With low-level vehicle automation already available, there is a necessity to estimate its effects on traffic flow, especially if these could be negative. A long gradual transition will occur from manual driving to automated driving, in which many yet unknown traffic flow dynamics will be present. These effects have the potential to increasingly aid or cripple current road networks. In this contribution, we investigate these effects using an empirically calibrated and validated simulation experiment, backed up with findings from literature. We found that low-level automated vehicles in mixed traffic will initially have a small negative effect on traffic flow and road capacities. The experiment further showed that any improvement in traffic flow will only be seen at penetration rates above 70%. Also, the capacity drop appeared to be slightly higher with the presence of low-level automated vehicles. The experiment further investigated the effect of bottleneck severity and truck shares on traffic flow. Improvements to current traffic models are recommended and should include a greater detail and understanding of driver-vehicle interaction, both in conventional and in mixed traffic flow. Further research into behavioural shifts in driving is also recommended due to limited data and knowledge of these dynamics.

  15. Negative probability of random multiplier in turbulence

    Science.gov (United States)

    Bai, Xuan; Su, Weidong

    2017-11-01

    The random multiplicative process (RMP), which has been proposed for over 50 years, is a convenient phenomenological ansatz of turbulence cascade. In the RMP, the fluctuation in a large scale is statistically mapped to the one in a small scale by the linear action of an independent random multiplier (RM). Simple as it is, the RMP is powerful enough since all of the known scaling laws can be included in this model. So far as we know, however, a direct extraction for the probability density function (PDF) of RM has been absent yet. The reason is the deconvolution during the process is ill-posed. Nevertheless, with the progress in the studies of inverse problems, the situation can be changed. By using some new regularization techniques, for the first time we recover the PDFs of the RMs in some turbulent flows. All the consistent results from various methods point to an amazing observation-the PDFs can attain negative values in some intervals; and this can also be justified by some properties of infinitely divisible distributions. Despite the conceptual unconventionality, the present study illustrates the implications of negative probability in turbulence in several aspects, with emphasis on its role in describing the interaction between fluctuations at different scales. This work is supported by the NSFC (No. 11221062 and No. 11521091).

  16. Universal corner contributions to entanglement negativity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Keun-Young, E-mail: fortoe@gist.ac.kr [School of Physics and Chemistry, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of); Niu, Chao, E-mail: chaoniu09@gmail.com [School of Physics and Chemistry, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of); Pang, Da-Wei, E-mail: d.pang@soton.ac.uk [Mathematical Sciences and STAG Research Centre, University of Southampton, Southampton SO17 1BJ (United Kingdom)

    2016-09-15

    It has been realised that corners in entangling surfaces can induce new universal contributions to the entanglement entropy and Rényi entropy. In this paper we study universal corner contributions to entanglement negativity in three- and four-dimensional CFTs using both field theory and holographic techniques. We focus on the quantity χ defined by the ratio of the universal part of the entanglement negativity over that of the entanglement entropy, which may characterise the amount of distillable entanglement. We find that for most of the examples χ takes bigger values for singular entangling regions, which may suggest increase in distillable entanglement. However, there also exist counterexamples where distillable entanglement decreases for singular surfaces. We also explore the behaviour of χ as the coupling varies and observe that for singular entangling surfaces, the amount of distillable entanglement is mostly largest for free theories, while counterexample exists for free Dirac fermion in three dimensions. For holographic CFTs described by higher derivative gravity, χ may increase or decrease, depending on the sign of the relevant parameters. Our results may reveal a more profound connection between geometry and distillable entanglement.

  17. Surgery and radiation therapy of triple-negative breast cancers: From biology to clinics

    NARCIS (Netherlands)

    Bernier, J.; Poortmans, P.M.P.

    2016-01-01

    Triple negative breast cancer refers to tumours lacking the expression of the three most used tumour markers, namely oestrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). These cancers are known to carry a more dismal prognosis than the other molecular

  18. Role of CD5-negative CD8 T Cells in Adaptation to Antigenic ...

    African Journals Online (AJOL)

    negative CD8. +. T Cells in Adaptation to. Antigenic Variation of Human Immunodeficiency Virus. Type 1. Xin-Yun Zhang1, Jian-Rong Zhao2, Yi-Le Xue3, Ying-Kui .... to a computer database. At the end of the programme, the data were analysed.

  19. Acute HIV-1 Infection in Antigen/Antibody-negative Blood Donors in ...

    African Journals Online (AJOL)

    Acute HIV-1 Infection in Antigen/Antibody-negative Blood Donors in Dar es Salaam, Tanzania. ... Fourth generation human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) enzyme-linked immunosorbent assay (ELISA) test used in the current screening of blood donors at the National Blood Transfusion Service ...

  20. Common Elements Enhance or Retard Negative Patterning Discrimination Learning Depending on Modality of Stimuli

    Science.gov (United States)

    Redhead, Edward S.; Curtis, Cheryl

    2013-01-01

    Human contingency learning studies were used to compare the predictions of configural and elemental theories. In two experiments, participants were required to learn which stimuli were associated with an increase in core temperature of a fictitious nuclear plant. Experiments investigated the rate at which a simple negative patterning…