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Sample records for human vap-c negatively

  1. Characterization of the Deep-Sea Streptomyces sp. SCSIO 02999 Derived VapC/VapB Toxin-Antitoxin System in Escherichia coli

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    Yunxue Guo

    2016-07-01

    Full Text Available Toxin-antitoxin (TA systems are small genetic elements that are ubiquitous in prokaryotes. Most studies on TA systems have focused on commensal and pathogenic bacteria; yet very few studies have focused on TAs in marine bacteria, especially those isolated from a deep sea environment. Here, we characterized a type II VapC/VapB TA system from the deep-sea derived Streptomyces sp. SCSIO 02999. The VapC (virulence-associated protein protein belongs to the PIN (PilT N-terminal superfamily. Overproduction of VapC strongly inhibited cell growth and resulted in a bleb-containing morphology in E. coli. The toxicity of VapC was neutralized through direct protein–protein interaction by a small protein antitoxin VapB encoded by a neighboring gene. Antitoxin VapB alone or the VapB/VapC complex negatively regulated the vapBC promoter activity. We further revealed that three conserved Asp residues in the PIN domain were essential for the toxic effect of VapC. Additionally, the VapC/VapB TA system stabilized plasmid in E. coli. Furthermore, VapC cross-activated transcription of several TA operons via a partially Lon-dependent mechanism in E. coli, and the activated toxins accumulated more preferentially than their antitoxin partners. Collectively, we identified and characterized a new deep sea TA system in the deep sea Streptomyces sp. and demonstrated that the VapC toxin in this system can cross-activate TA operons in E. coli.

  2. Characterization of the Deep-Sea Streptomyces sp. SCSIO 02999 Derived VapC/VapB Toxin-Antitoxin System in Escherichia coli.

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    Guo, Yunxue; Yao, Jianyun; Sun, Chenglong; Wen, Zhongling; Wang, Xiaoxue

    2016-07-01

    Toxin-antitoxin (TA) systems are small genetic elements that are ubiquitous in prokaryotes. Most studies on TA systems have focused on commensal and pathogenic bacteria; yet very few studies have focused on TAs in marine bacteria, especially those isolated from a deep sea environment. Here, we characterized a type II VapC/VapB TA system from the deep-sea derived Streptomyces sp. SCSIO 02999. The VapC (virulence-associated protein) protein belongs to the PIN (PilT N-terminal) superfamily. Overproduction of VapC strongly inhibited cell growth and resulted in a bleb-containing morphology in E. coli. The toxicity of VapC was neutralized through direct protein-protein interaction by a small protein antitoxin VapB encoded by a neighboring gene. Antitoxin VapB alone or the VapB/VapC complex negatively regulated the vapBC promoter activity. We further revealed that three conserved Asp residues in the PIN domain were essential for the toxic effect of VapC. Additionally, the VapC/VapB TA system stabilized plasmid in E. coli. Furthermore, VapC cross-activated transcription of several TA operons via a partially Lon-dependent mechanism in E. coli, and the activated toxins accumulated more preferentially than their antitoxin partners. Collectively, we identified and characterized a new deep sea TA system in the deep sea Streptomyces sp. and demonstrated that the VapC toxin in this system can cross-activate TA operons in E. coli.

  3. VapC toxins drive cellular dormancy under uranium stress for the extreme thermoacidophile Metallosphaera prunae.

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    Mukherjee, Arpan; Wheaton, Garrett H; Counts, James A; Ijeomah, Brenda; Desai, Jigar; Kelly, Robert M

    2017-07-01

    When abruptly exposed to toxic levels of hexavalent uranium, the extremely thermoacidophilic archaeon Metallosphaera prunae, originally isolated from an abandoned uranium mine, ceased to grow, and concomitantly exhibited heightened levels of cytosolic ribonuclease activity that corresponded to substantial degradation of cellular RNA. The M. prunae transcriptome during 'uranium-shock' implicated VapC toxins as possible causative agents of the observed RNA degradation. Identifiable VapC toxins and PIN-domain proteins encoded in the M. prunae genome were produced and characterized, three of which (VapC4, VapC7, VapC8) substantially degraded M. prunae rRNA in vitro. RNA cleavage specificity for these VapCs mapped to motifs within M. prunae rRNA. Furthermore, based on frequency of cleavage sequences, putative target mRNAs for these VapCs were identified; these were closely associated with translation, transcription, and replication. It is interesting to note that Metallosphaera sedula, a member of the same genus and which has a nearly identical genome sequence but not isolated from a uranium-rich biotope, showed no evidence of dormancy when exposed to this metal. M. prunae utilizes VapC toxins for post-transcriptional regulation under uranium stress to enter a cellular dormant state, thereby providing an adaptive response to what would otherwise be a deleterious environmental perturbation. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

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

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

    2016-01-01

    The VapC toxin from the Shigella flexneri 2a virulence plasmid pMYSH6000 belongs to the PIN domain protein family, which is characterized by a conserved fold with low amino acid sequence conservation. The toxin is a bona fide Mg2+-dependent ribonuclease and has been shown to target initiator t...

  5. VapC from the leptospiral VapBC toxin-antitoxin module displays ribonuclease activity on the initiator tRNA.

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    Alexandre P Y Lopes

    Full Text Available The prokaryotic ubiquitous Toxin-Antitoxin (TA operons encode a stable toxin and an unstable antitoxin. The most accepted hypothesis of the physiological function of the TA system is the reversible cessation of cellular growth under stress conditions. The major TA family, VapBC is present in the spirochaete Leptospira interrogans. VapBC modules are classified based on the presence of a predicted ribonucleasic PIN domain in the VapC toxin. The expression of the leptospiral VapC in E. coli promotes a strong bacterial growth arrestment, making it difficult to express the recombinant protein. Nevertheless, we showed that long term induction of expression in E. coli enabled the recovery of VapC in inclusion bodies. The recombinant protein was successfully refolded by high hydrostatic pressure, providing a new method to obtain the toxin in a soluble and active form. The structural integrity of the recombinant VapB and VapC proteins was assessed by circular dichroism spectroscopy. Physical interaction between the VapC toxin and the VapB antitoxin was demonstrated in vivo and in vitro by pull down and ligand affinity blotting assays, respectively, thereby indicating the ultimate mechanism by which the activity of the toxin is regulated in bacteria. The predicted model of the leptospiral VapC structure closely matches the Shigella's VapC X-ray structure. In agreement, the ribonuclease activity of the leptospiral VapC was similar to the activity described for Shigella's VapC, as demonstrated by the cleavage of tRNAfMet and by the absence of unspecific activity towards E. coli rRNA. This finding suggests that the cleavage of the initiator transfer RNA may represent a common mechanism to a larger group of bacteria and potentially configures a mechanism of post-transcriptional regulation leading to the inhibition of global translation.

  6. Analysis of non-typeable Haemophilous influenzae VapC1 mutations reveals structural features required for toxicity and flexibility in the active site.

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    Brooke Hamilton

    Full Text Available Bacteria have evolved mechanisms that allow them to survive in the face of a variety of stresses including nutrient deprivation, antibiotic challenge and engulfment by predator cells. A switch to dormancy represents one strategy that reduces energy utilization and can render cells resistant to compounds that kill growing bacteria. These persister cells pose a problem during treatment of infections with antibiotics, and dormancy mechanisms may contribute to latent infections. Many bacteria encode toxin-antitoxin (TA gene pairs that play an important role in dormancy and the formation of persisters. VapBC gene pairs comprise the largest of the Type II TA systems in bacteria and they produce a VapC ribonuclease toxin whose activity is inhibited by the VapB antitoxin. Despite the importance of VapBC TA pairs in dormancy and persister formation, little information exists on the structural features of VapC proteins required for their toxic function in vivo. Studies reported here identified 17 single mutations that disrupt the function of VapC1 from non-typeable H. influenzae in vivo. 3-D modeling suggests that side chains affected by many of these mutations sit near the active site of the toxin protein. Phylogenetic comparisons and secondary mutagenesis indicate that VapC1 toxicity requires an alternative active site motif found in many proteobacteria. Expression of the antitoxin VapB1 counteracts the activity of VapC1 mutants partially defective for toxicity, indicating that the antitoxin binds these mutant proteins in vivo. These findings identify critical chemical features required for the biological function of VapC toxins and PIN-domain proteins.

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

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    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.

  8. Quantum Structure of Negation and Conjunction in Human Thought

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    Diederik eAerts

    2015-09-01

    Full Text Available We analyze in this paper the data collected in a set of experiments investigating how people combine natural concepts. We study the mutual influence of conceptual conjunction and negation by measuring the membership weights of a list of exemplars with respect to two concepts, e.g., {it Fruits} and {it Vegetables}, and their conjunction {it Fruits And Vegetables}, but also their conjunction when one or both concepts are negated, namely, {it Fruits And Not Vegetables}, {it Not Fruits And Vegetables} and {it Not Fruits And Not Vegetables}. Our findings sharpen and advance existing analysis on conceptual combinations, revealing systematic deviations from classical (fuzzy set logic and probability theory. And, more important, our results give further considerable evidence to the validity of our quantum-theoretic framework for the combination of two concepts. Indeed, the representation of conceptual negation naturally arises from the general assumptions of our two-sector Fock space model, and this representation faithfully agrees with the collected data. In addition, we find a new significant and a priori unexpected deviation from classicality, which can exactly be explained by assuming that human reasoning is the superposition of an `emergent reasoning' and a `logical reasoning', and that these two processes are represented in a Fock space algebraic structure.

  9. Quantum structure of negation and conjunction in human thought

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    Aerts, Diederik; Sozzo, Sandro; Veloz, Tomas

    2015-01-01

    We analyze in this paper the data collected in a set of experiments investigating how people combine natural concepts. We study the mutual influence of conceptual conjunction and negation by measuring the membership weights of a list of exemplars with respect to two concepts, e.g., Fruits and Vegetables, and their conjunction Fruits And Vegetables, but also their conjunction when one or both concepts are negated, namely, Fruits And Not Vegetables, Not Fruits And Vegetables, and Not Fruits And Not Vegetables. Our findings sharpen and advance existing analysis on conceptual combinations, revealing systematic deviations from classical (fuzzy set) logic and probability theory. And, more important, our results give further considerable evidence to the validity of our quantum-theoretic framework for the combination of two concepts. Indeed, the representation of conceptual negation naturally arises from the general assumptions of our two-sector Fock space model, and this representation faithfully agrees with the collected data. In addition, we find a new significant and a priori unexpected deviation from classicality, which can exactly be explained by assuming that human reasoning is the superposition of an “emergent reasoning” and a “logical reasoning,” and that these two processes are represented in a Fock space algebraic structure. PMID:26483715

  10. Excessive Cellular Proliferation Negatively Impacts Reprogramming Efficiency of Human Fibroblasts.

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    Gupta, Manoj K; Teo, Adrian Kee Keong; Rao, Tata Nageswara; Bhatt, Shweta; Kleinridders, Andre; Shirakawa, Jun; Takatani, Tomozumi; Hu, Jiang; De Jesus, Dario F; Windmueller, Rebecca; Wagers, Amy J; Kulkarni, Rohit N

    2015-10-01

    The impact of somatic cell proliferation rate on induction of pluripotent stem cells remains controversial. Herein, we report that rapid proliferation of human somatic fibroblasts is detrimental to reprogramming efficiency when reprogrammed using a lentiviral vector expressing OCT4, SOX2, KLF4, and cMYC in insulin-rich defined medium. Human fibroblasts grown in this medium showed higher proliferation, enhanced expression of insulin signaling and cell cycle genes, and a switch from glycolytic to oxidative phosphorylation metabolism, but they displayed poor reprogramming efficiency compared with cells grown in normal medium. Thus, in contrast to previous studies, our work reveals an inverse correlation between the proliferation rate of somatic cells and reprogramming efficiency, and also suggests that upregulation of proteins in the growth factor signaling pathway limits the ability to induce pluripotency in human somatic fibroblasts. The efficiency with which human cells can be reprogrammed is of interest to stem cell biology. In this study, human fibroblasts cultured in media containing different concentrations of growth factors such as insulin and insulin-like growth factor-1 exhibited variable abilities to proliferate, with consequences on pluripotency. This occurred in part because of changes in the expression of proteins involved in the growth factor signaling pathway, glycolysis, and oxidative phosphorylation. These findings have implications for efficient reprogramming of human cells. ©AlphaMed Press.

  11. Oxidative stress negatively affects human sperm mitochondrial respiration.

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    Ferramosca, Alessandra; Pinto Provenzano, Sara; Montagna, Daniela Domenica; Coppola, Lamberto; Zara, Vincenzo

    2013-07-01

    To correlate the level of oxidative stress in serum and seminal fluid and the level of sperm deoxyribonucleic acid (DNA) fragmentation with sperm mitochondrial respiratory efficiency. Sperm mitochondrial respiratory activity was evaluated with a polarographic assay of oxygen consumption carried out in hypotonically treated sperm cells. A possible relationship between sperm mitochondrial respiratory efficiency, the level of oxidative stress, and the level of sperm DNA fragmentation was investigated. Sperm motility was positively correlated with mitochondrial respiration but negatively correlated with oxidative stress and DNA fragmentation. Interestingly, sperm mitochondrial respiratory activity was negatively affected by oxidative stress and DNA fragmentation. Our data indicate that sperm mitochondrial respiration is decreased in patients with high levels of reactive oxygen species by an uncoupling between electron transport and adenosine triphosphate synthesis. This reduction in mitochondrial functionality might be 1 of the reasons responsible for the decrease in spermatozoa motility. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Temporal span of human echoic memory and mismatch negativity: revisited.

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    Jääskeläinen, I P; Hautamäki, M; Näätänen, R; Ilmoniemi, R J

    1999-04-26

    The stimulus onset asynchrony (SOA)-related decrease in mismatch negativity (MMN) amplitude has been used to infer a putative auditory sensory memory duration of 4-10 s. However, both increased standard-to-standard (SSA) and standard-to-deviant (SDA) gaps could contribute to the effect. Fourteen subjects were presented with standard and deviant tones with short (0.35 s) and long (3.5 s) SOAs. In addition, the SSA and SDA were separately manipulated to test the relative contributions of slower rate of standard tone presentation and longer SDA gap to the SOA-related decrease in MMN amplitude. The MMN amplitude decreased with long SOA by 61%. Increases in SSA and SDA resulted in intermediate 47% and 31% decreases, these manipulations explaining 67% of the long SOA effect (pechoic memory length cannot be directly inferred from an MMN-SOA dependency function.

  13. Human amygdala response to dynamic facial expressions of positive and negative surprise.

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    Vrticka, Pascal; Lordier, Lara; Bediou, Benoît; Sander, David

    2014-02-01

    Although brain imaging evidence accumulates to suggest that the amygdala plays a key role in the processing of novel stimuli, only little is known about its role in processing expressed novelty conveyed by surprised faces, and even less about possible interactive encoding of novelty and valence. Those investigations that have already probed human amygdala involvement in the processing of surprised facial expressions either used static pictures displaying negative surprise (as contained in fear) or "neutral" surprise, and manipulated valence by contextually priming or subjectively associating static surprise with either negative or positive information. Therefore, it still remains unresolved how the human amygdala differentially processes dynamic surprised facial expressions displaying either positive or negative surprise. Here, we created new artificial dynamic 3-dimensional facial expressions conveying surprise with an intrinsic positive (wonderment) or negative (fear) connotation, but also intrinsic positive (joy) or negative (anxiety) emotions not containing any surprise, in addition to neutral facial displays either containing ("typical surprise" expression) or not containing ("neutral") surprise. Results showed heightened amygdala activity to faces containing positive (vs. negative) surprise, which may either correspond to a specific wonderment effect as such, or to the computation of a negative expected value prediction error. Findings are discussed in the light of data obtained from a closely matched nonsocial lottery task, which revealed overlapping activity within the left amygdala to unexpected positive outcomes. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  14. Comparison between Human Immunodeficiency Virus Positive and Negative Patients with Tuberculosis in Southern Brazil

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    Lucélia Henn

    1999-05-01

    Full Text Available The objective of this study is to determine the different characteristics of human immunodeficiency virus (HIV positive and negative patients treated for tuberculosis (TBC in a tertiary hospital in Southern Brazil. We conducted a retrospective cohort study over a 5-year period, from January 1992 through December 1996. We reviewed medical charts of patients from our institution who received TBC treatment. We reviewed 167 medical charts of patients with confirmed TBC. HIV positivity was detected in 74 patients. There were statistically significant difference between HIV positive and negative patients in sex and age. HIV-infected patients showed significantly more signs of bacteremia than HIV-negative patients. Extra-pulmonary TBC was present respectively in 13 (17.6% and 21 (22.6% HIV positive and negative patients. There was a significant difference between chest radiograph presentation in HIV positive and negative patients. There were significantly lower hematocrit, hemoglobin, leukocyte and lymphocyte levels in HIV-positive compared to HIV-negative patients. Outcome was significantly different in the two groups with a death rate of 36.5% and 10.8% in HIV-positive and in HIV-negative patients. The difference between HIV positive and negative patients may have importance in the diagnosis, management and prognosis of patients with TBC.

  15. Simultaneous and Sequential Feature Negative Discriminations: Elemental Learning and Occasion Setting in Human Pavlovian Conditioning

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    Baeyens, Frank; Vervliet, Bram; Vansteenwegen, Debora; Beckers, Tom; Hermans, Dirk; Eelen, Paul

    2004-01-01

    Using a conditioned suppression task, we investigated simultaneous (XA-/A+) vs. sequential (X [right arrow] A-/A+) Feature Negative (FN) discrimination learning in humans. We expected the simultaneous discrimination to result in X (or alternatively the XA configuration) becoming an inhibitor acting directly on the US, and the sequential…

  16. Antibody reaction of human anti-Toxoplasma gondii positive and negative sera with Neospora caninum antigens

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    Nam, Ho-Woo; Kang, Seung-Won; Choi, Won-Young

    1998-01-01

    Anti-Neospora caninum antibody was detected in anti-Toxoplasma gondii positive and negative human sera by ELISA, western blot and immunofluorescence assay (IFA). Twelve cases out of 172 (6.7%) Toxoplasma-positive sera cross-reacted with both T. gondii and N. caninum antigens, and one out of 110 Toxoplasma-negative sera reacted with N. caninum antigen by ELISA. By western blot, all 12 sera reacted with T. gondii antigens with various banding patterns but specifically at 30 kDa (SAG1) and 22 kD...

  17. Reassurance against future risk of precancer and cancer conferred by a negative human papillomavirus test.

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    Gage, Julia C; Schiffman, Mark; Katki, Hormuzd A; Castle, Philip E; Fetterman, Barbara; Wentzensen, Nicolas; Poitras, Nancy E; Lorey, Thomas; Cheung, Li C; Kinney, Walter K

    2014-08-01

    Primary human papillomavirus (HPV) testing (without concurrent Pap tests) every 3 years is under consideration in the United States as an alternative to the two recommended cervical cancer screening strategies: primary Pap testing every 3 years, or concurrent Pap and HPV testing ("cotesting") every 5 years. Using logistic regression and Weibull survival models, we estimated and compared risks of cancer and cervical intraepithelial neoplasia grade 3 or worse (CIN3+) for the three strategies among 1011092 women aged 30 to 64 years testing HPV-negative and/or Pap-negative in routine screening at Kaiser Permanente Northern California since 2003. All statistical tests were two sided. Three-year risks following an HPV-negative result were lower than 3-year risks following a Pap-negative result (CIN3+ = 0.069% vs 0.19%, P < .0001; Cancer = 0.011% vs 0.020%, P < .0001) and 5-year risks following an HPV-negative/Pap-negative cotest (CIN3+ = 0.069% vs 0.11%, P < .0001; Cancer = 0.011% vs 0.014%, P = .21). These findings suggest that primary HPV testing merits consideration as another alternative for cervical screening. © Published by Oxford University Press 2014.

  18. Partial hydatidiform mole with false-negative urine human chorionic gonadatropin test in the emergency department.

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    Mundangepfupfu, Tichaendepi; Waseem, Muhammad

    2014-03-01

    Hydatidiform mole (molar pregnancy) is a benign tumor of placental trophoblastic cells, which release human chorionic gonadotropin (hCG). Several case reports have described complete hydatidiform moles with false-negative urine qualitative hCG tests. These negative pregnancy tests have been attributed to the hook effect. We report an unusual presentation of a partial mole and review an alternative explanation for the negative hCG test. As partial moles are usually not associated with a large proliferation of trophoblastic cells, levels of hCG are commonly negative and serum quantitative hCG was 1,094,950 mIU/mL. Pelvic ultrasonography showed a uterine cavity containing a soft-tissue mass with multiple cystic lesions and the hydatidiform mole was extracted with suction curettage. Tissue pathology confirmed partial hydatidiform mole. In addition to the hook effect, we present another possible explanation for the false-negative test; namely the inability of some assays to detect hCG-degradation products, which may be higher in clinical samples from patients with hydatidiform mole. This case underscores the importance of knowing the limitations of the commonly used hCG assays. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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    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. Prospectively Isolated Human Bone Marrow Cell-Derived MSCs Support Primitive Human CD34-Negative Hematopoietic Stem Cells.

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    Matsuoka, Yoshikazu; Nakatsuka, Ryusuke; Sumide, Keisuke; Kawamura, Hiroshi; Takahashi, Masaya; Fujioka, Tatsuya; Uemura, Yasushi; Asano, Hiroaki; Sasaki, Yutaka; Inoue, Masami; Ogawa, Hiroyasu; Takahashi, Takayuki; Hino, Masayuki; Sonoda, Yoshiaki

    2015-05-01

    Hematopoietic stem cells (HSCs) are maintained in a specialized bone marrow (BM) niche, which consists of osteoblasts, endothelial cells, and a variety of mesenchymal stem/stromal cells (MSCs). However, precisely what types of MSCs support human HSCs in the BM remain to be elucidated because of their heterogeneity. In this study, we succeeded in prospectively isolating/establishing three types of MSCs from human BM-derived lineage- and CD45-negative cells, according to their cell surface expression of CD271 and stage-specific embryonic antigen (SSEA)-4. Among them, the MSCs established from the Lineage(-) CD45(-) CD271(+) SSEA-4(+) fraction (DP MSC) could differentiate into osteoblasts and chondrocytes, but they lacked adipogenic differentiation potential. The DP MSCs expressed significantly higher levels of well-characterized HSC-supportive genes, including IGF-2, Wnt3a, Jagged1, TGFβ3, nestin, CXCL12, and Foxc1, compared with other MSCs. Interestingly, these osteo-chondrogenic DP MSCs possessed the ability to support cord blood-derived primitive human CD34-negative severe combined immunodeficiency-repopulating cells. The HSC-supportive actions of DP MSCs were partially carried out by soluble factors, including IGF-2, Wnt3a, and Jagged1. Moreover, contact between DP MSCs and CD34-positive (CD34(+) ) as well as CD34-negative (CD34(-) ) HSCs was important for the support/maintenance of the CD34(+/-) HSCs in vitro. These data suggest that DP MSCs might play an important role in the maintenance of human primitive HSCs in the BM niche. Therefore, the establishment of DP MSCs provides a new tool for the elucidation of the human HSC/niche interaction in vitro as well as in vivo. © 2014 AlphaMed Press.

  1. The negative ultraslow potential, electrophysiological correlate of infarction in the human cortex.

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    Lückl, Janos; Lemale, Coline L; Kola, Vasilis; Horst, Viktor; Khojasteh, Uldus; Oliveira-Ferreira, Ana I; Major, Sebastian; Winkler, Maren K L; Kang, Eun-Jeung; Schoknecht, Karl; Martus, Peter; Hartings, Jed A; Woitzik, Johannes; Dreier, Jens P

    2018-06-01

    Spreading depolarizations are characterized by abrupt, near-complete breakdown of the transmembrane ion gradients, neuronal oedema, mitochondrial depolarization, glutamate excitotoxicity and activity loss (depression). Spreading depolarization induces either transient hyperperfusion in normal tissue; or hypoperfusion (inverse coupling = spreading ischaemia) in tissue at risk for progressive injury. The concept of the spreading depolarization continuum is critical since many spreading depolarizations have intermediate characteristics, as opposed to the two extremes of spreading depolarization in either severely ischaemic or normal tissue. In animals, the spreading depolarization extreme in ischaemic tissue is characterized by prolonged depolarization durations, in addition to a slow baseline variation termed the negative ultraslow potential. The negative ultraslow potential is initiated by spreading depolarization and similar to the negative direct current (DC) shift of prolonged spreading depolarization, but specifically refers to a negative potential component during progressive recruitment of neurons into cell death in the wake of spreading depolarization. We here first quantified the spreading depolarization-initiated negative ultraslow potential in the electrocorticographic DC range and the activity depression in the alternate current range after middle cerebral artery occlusion in rats. Relevance of these variables to the injury was supported by significant correlations with the cortical infarct volume and neurological outcome after 72 h of survival. We then identified negative ultraslow potential-containing clusters of spreading depolarizations in 11 patients with aneurysmal subarachnoid haemorrhage. The human platinum/iridium-recorded negative ultraslow potential showed a tent-like shape. Its amplitude of 45.0 (39.0, 69.4) mV [median (first, third quartile)] was 6.6 times larger and its duration of 3.7 (3.3, 5.3) h was 34.9 times longer than the negative DC

  2. 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.

  3. 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

  4. Bloodstains on Leather: Examination of False Negatives in Presumptive Test and Human Hemoglobin Test.

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    Castelló, Ana; Francès, Francesc; Verdú, Fernando

    2017-09-01

    Presumptive tests for blood are very simple and sensitive tests used in the search for evidence. They also provide initial information on the nature of stains. A second test can confirm their nature. However, these tests can present false-negative results for different reasons. Some of those reasons have been studied, while others, those caused by the substrate material that contains the stain, are less well known. This work studies the effect of one component of a leather substrate-quebracho extract-on presumptive and human hemoglobin blood tests. Assays were performed using samples of blood dilutions contaminated with quebracho extract and others formed on a substrate containing the contaminant. Results show an undoubted interference that causes false negatives and even visible to the naked eye stains and also indicate that some tests (phenolphthalein) are more affected than others. Examiners should be taken into account when working on this kind of substrates. © 2017 American Academy of Forensic Sciences.

  5. Blocking negative effects of senescence in human skin fibroblasts with a plant extract.

    Science.gov (United States)

    Lämmermann, Ingo; Terlecki-Zaniewicz, Lucia; Weinmüllner, Regina; Schosserer, Markus; Dellago, Hanna; de Matos Branco, André Dargen; Autheried, Dominik; Sevcnikar, Benjamin; Kleissl, Lisa; Berlin, Irina; Morizot, Frédérique; Lejeune, Francois; Fuzzati, Nicola; Forestier, Sandra; Toribio, Alix; Tromeur, Anaïs; Weinberg, Lionel; Higareda Almaraz, Juan Carlos; Scheideler, Marcel; Rietveld, Marion; El Ghalbzouri, Abdoel; Tschachler, Erwin; Gruber, Florian; Grillari, Johannes

    2018-01-01

    There is increasing evidence that senescent cells are a driving force behind many age-related pathologies and that their selective elimination increases the life- and healthspan of mice. Senescent cells negatively affect their surrounding tissue by losing their cell specific functionality and by secreting a pro-tumorigenic and pro-inflammatory mixture of growth hormones, chemokines, cytokines and proteases, termed the senescence-associated secretory phenotype (SASP). Here we identified an extract from the plant Solidago virgaurea subsp. alpestris , which exhibited weak senolytic activity, delayed the acquisition of a senescent phenotype and induced a papillary phenotype with improved functionality in human dermal fibroblasts. When administered to stress-induced premature senescent fibroblasts, this extract changed their global mRNA expression profile and particularly reduced the expression of various SASP components, thereby ameliorating the negative influence on nearby cells. Thus, the investigated plant extract represents a promising possibility to block age-related loss of tissue functionality.

  6. Overlapping positive and negative regulatory domains of the human β-interferon gene

    International Nuclear Information System (INIS)

    Goodbourn, S.; Maniatis, T.

    1988-01-01

    Virus of poly(I) x poly(C) induction of human β-interferon gene expression requires a 40-base-pair DNA sequence designated the interferon gene regulatory element (IRE). Previous studies have shown that the IRE contains both positive and negative regulatory DNA sequences. To localize these sequences and study their interactions, the authors have examined the effects of a large number of single-base mutations within the IRE on β-interferon gene regulation. They find that the IRE consists of two genetically separable positive regulatory domains and an overlapping negative control sequence. They propose that the β-interferon gene is switched off in uninduced cells by a repressor that blocks the interaction between one of the two positive regulatory sequences and a specific transcription factor. Induction would then lead to inactivation or displacement of the repressor and binding of transcription factors to both positive regulatory domains

  7. CD133 (Prominin negative human neural stem cells are clonogenic and tripotent.

    Directory of Open Access Journals (Sweden)

    Yirui Sun

    Full Text Available CD133 (Prominin is widely used as a marker for the identification and isolation of neural precursor cells from normal brain or tumor tissue. However, the assumption that CD133 is expressed constitutively in neural precursor cells has not been examined.In this study, we demonstrate that CD133 and a second marker CD15 are expressed heterogeneously in uniformly undifferentiated human neural stem (NS cell cultures. After fractionation by flow cytometry, clonogenic tripotent cells are found in populations negative or positive for either marker. We further show that CD133 is down-regulated at the mRNA level in cells lacking CD133 immunoreactivity. Cell cycle profiling reveals that CD133 negative cells largely reside in G1/G0, while CD133 positive cells are predominantly in S, G2, or M phase. A similar pattern is apparent in mouse NS cell lines. Compared to mouse NS cells, however, human NS cell cultures harbour an increased proportion of CD133 negative cells and display a longer doubling time. This may in part reflect a sub-population of slow- or non-cycling cells amongst human NS cells because we find that around 5% of cells do not take up BrdU over a 14-day labelling period. Non-proliferating NS cells remain undifferentiated and at least some of them are capable of re-entry into the cell cycle and subsequent continuous expansion.The finding that a significant fraction of clonogenic neural stem cells lack the established markers CD133 and CD15, and that some of these cells may be dormant or slow-cycling, has implications for approaches to identify and isolate neural stem cells and brain cancer stem cells. Our data also suggest the possibility that CD133 may be specifically down-regulated during G0/G1, and this should be considered when this marker is used to identify and isolate other tissue and cancer stem cells.

  8. Annual Papanicolaou screening for 5 years among human papillomavirus-negative women

    International Nuclear Information System (INIS)

    Petry, Karl Ulrich; Rinnau, Franziska; Böhmer, Gerd; Hollwitz, Bettina; Luyten, Alexander; Buttmann, Nina; Brünger, Martin; Iftner, Thomas

    2013-01-01

    Primary human papilloma virus (HPV) screening is more effective than cytology in reducing the risk of cervical cancer, but screening intervals should be extended in HPV-negative women. However, some Markov models predicted that long intervals are associated with an excess risk of cervical cancer. The aim of this analysis was to estimate the real-life risks and benefits of annual Papanicolaou (Pap) screening in HPV-negative women with normal cytology. Women with negative Hybrid Capture 2 (HC2) results and normal cytology at the time of inclusion in the Hannover HPV screening trial underwent annual Pap smears for 5 years. A subgroup was randomly selected for retesting with cytology, HC2, and colposcopy 60–68 months after recruitment. Of 4236 women included, 3406 had at least one Pap smear, but only 1185 attended all five annual screening visits. The proportion of women with at least one abnormal smear was 14.4% in 60 months. The probability of abnormal smears increased continuously over time. No case of ≥ CIN2+ was observed during 5 years. Of 605 women selected for subgroup analysis, 292 agreed to be retested (48.3%). The rate of high-risk HPV at 60–68 months was 3.0% (9/296). The long-term risk of high-grade neoplasia after an initial negative HC2 test and normal cytology result was low, while the rate of false-positive abnormal Pap smears was significant and increased constantly over time. Pap smear screening of HPV-negative women more frequently than every 5 years could be potentially harmful and seems to be of little clinical value

  9. Characterization of the positive and negative inotropic effects of acetylcholine in the human myocardium

    OpenAIRE

    Du, Xiaoyi; Schoemaker, Regien; Bos, Egbert; Saxena, Pramod Ranjan

    1995-01-01

    textabstractIn the human isolated myocardium, acetylcholine (10−9 to 10−3 M) elicited a biphasic inotropic effect (a decrease in the lower and an increase in the higher concentration range) in atrial and a positive inotropic effect in ventricular trabeculae. However, under conditions of raised contractility achieved by exposure to noradrenaline (10−5 M), only negative inotropic effects were observed in both atria and ventricles. Atropine (10−6 M), but not propranolol (10−6 M), antagonized bot...

  10. A case study of human immunodeficiency virus with positive seroconversion to negative

    Directory of Open Access Journals (Sweden)

    Paranthaman Vengadasalam

    2015-07-01

    Full Text Available This case study demonstrates a 36-year-old ex-intravenous drug user (IVDU who had been initially tested positive for human immunodeficiency virus (HIV twice using Enzyme Immunoassay (EIA method (Particle agglutination, PA done, but a year later he was tested HIV-negative. The patient was asymptomatic for HIV and T helper cells (CD4 count remained stable throughout this period. In light of this case, there may be a need to retest by molecular methods for high risk category patients who were initially diagnosed HIV-positive, but later showing an unexpected clinical course, such as a rising or stable CD4 titre over the years.

  11. Comparison of Tuberculin Skin Test result and interferon gamma response to human PPD in BCG scar positive and negative children.

    Science.gov (United States)

    Sayyahfar, Shirin; Karimi, Abdollah; Fahimzad, Alireza; Shamshiri, Ahmad Reza

    2014-03-01

    The aim of this study is to compare Tuberculin Skin Test (TST) result and interferon gamma response to human PPD (purified protein derivative), in scar positive and scar negative BCG-vaccinated children. Between August 2007 and May 2008 a total of 236 children aged 1-168 months (mean 21 months) admitted to Mofid Children's Hospital, Tehran, Iran, were enrolled in a cross-sectional study. Each patient was examined for BCG vaccine scar and tested with TST and human PPD-based Interferon Gamma Release Assay (IGRA). Two hundred and twenty one cases out of 236 (44% female, 1-168 months, mean age 21 months) were scar positive of whom 95% TST result was negative. Human PPD-based IGRA was positive in 110 (49.8%), negative in 85 (38.4 %) and indeterminate in 26 (11.8%) of scar positive patients. Fifteen children (40% female, 1-156 months; mean age 42 months) were scar negative. All the scar negative cases were TST negative. Human PPD-based IGRA was positive in 10 (66.7%), negative in 4 (26.7%) and indeterminate in 1 (6.7%) of scar negative patients. Immune responsiveness to human PPD antigens in scar positive and negative children may not correspond with results of the Tuberculin Skin Test. Copyright © 2013 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  12. Electrical admittance for filling of the heart during lower body negative pressure in humans

    DEFF Research Database (Denmark)

    Cai, Yujia; Holm, S; Jenstrup, M

    2000-01-01

    To evaluate whether electrical admittance of intracellular water is applicable for monitoring filling of the heart, we determined the difference in intracellular water in the thorax (Thorax(ICW)), measured as the reciprocal value of the electrical impedance for the thorax at 1.5 and 100 kHz during...... lower body negative pressure (LBNP) in humans. Changes in Thorax(ICW) were compared with positron emission tomography-determined C(15)O-labeled erythrocytes over the heart. During -40 mmHg LBNP, the blood volume of the heart decreased by 21 +/- 3% as the erythrocyte volume was reduced by 20 +/- 2.......6 to 40.9 +/- 5.0 S. 10(-4); P = 0.08). The correlation between Thorax(ICW) and heart erythrocyte volume was 0.84 (P electrical admittance of intracellular water can be applied to evaluate changes in blood volume of the heart during LBNP in humans....

  13. 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

  14. Negative regulation of human parathyroid hormone gene promoter by vitamin D3 through nuclear factor Y

    International Nuclear Information System (INIS)

    Jaeaeskelaeinen, T.; Huhtakangas, J.; Maeenpaeae, P.H.

    2005-01-01

    The negative regulation of the human parathyroid hormone (PTH) gene by biologically active vitamin D 3 (1,25-dihydroxyvitamin D 3 ; 1,25(OH) 2 D 3 ) was studied in rat pituitary GH4C1 cells, which express factors needed for the negative regulation. We report here that NF-Y binds to sequences downstream of the site previously reported to bind the vitamin D receptor (VDR). Additional binding sites for NF-Y reside in the near vicinity and were shown to be important for full activity of the PTH gene promoter. VDR and NF-Y were shown to exhibit mutually exclusive binding to the VDRE region. According to our results, sequestration of binding partners for NF-Y by VDR also affects transcription through a NF-Y consensus binding element in GH4C1 but not in ROS17/2.8 cells. These results indicate that 1,25(OH) 2 D 3 may affect transcription of the human PTH gene both by competitive binding of VDR and NF-Y, and by modulating transcriptional activity of NF-Y

  15. A General Model of Negative Frequency Dependent Selection Explains Global Patterns of Human ABO Polymorphism.

    Directory of Open Access Journals (Sweden)

    Fernando A Villanea

    Full Text Available The ABO locus in humans is characterized by elevated heterozygosity and very similar allele frequencies among populations scattered across the globe. Using knowledge of ABO protein function, we generated a simple model of asymmetric negative frequency dependent selection and genetic drift to explain the maintenance of ABO polymorphism and its loss in human populations. In our models, regardless of the strength of selection, models with large effective population sizes result in ABO allele frequencies that closely match those observed in most continental populations. Populations must be moderately small to fall out of equilibrium and lose either the A or B allele (N(e ≤ 50 and much smaller (N(e ≤ 25 for the complete loss of diversity, which nearly always involved the fixation of the O allele. A pattern of low heterozygosity at the ABO locus where loss of polymorphism occurs in our model is consistent with small populations, such as Native American populations. This study provides a general evolutionary model to explain the observed global patterns of polymorphism at the ABO locus and the pattern of allele loss in small populations. Moreover, these results inform the range of population sizes associated with the recent human colonization of the Americas.

  16. 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.

  17. Src-family kinases negatively regulate NFAT signaling in resting human T cells.

    Directory of Open Access Journals (Sweden)

    Alan Baer

    Full Text Available T cell signaling is required for activation of both natural and therapeutic T cells including chimeric antigen receptor (CAR T cells. Identification of novel factors and pathways regulating T cell signaling may aid in development of effective T cell therapies. In resting human T cells, the majority of Src-family of tyrosine kinases (SFKs are inactive due to phosphorylation of a conserved carboxy-terminal tyrosine residue. Recently, a pool of enzymatically active SFKs has been identified in resting T cells; however, the significance of these is incompletely understood. Here, we characterized the role of active SFKs in resting human T cells. Pharmacologic inhibition of active SFKs enhanced distal TCR signaling as measured by IL-2 release and CD25 surface expression following TCR-independent activation. Mechanistically, inhibition of the active pool of SFKs induced nuclear translocation of NFAT1, and enhanced NFAT1-dependent signaling in resting T cells. The negative regulation of NFAT1 signaling was in part mediated by the Src-kinase Lck as human T cells lacking Lck had increased levels of nuclear NFAT1 and demonstrated enhanced NFAT1-dependent gene expression. Inhibition of active SFKs in resting primary human T cells also increased nuclear NFAT1 and enhanced NFAT1-dependent signaling. Finally, the calcineurin inhibitor FK506 and Cyclosporin A reversed the effect of SFKs inhibition on NFAT1. Together, these data identified a novel role of SFKs in preventing aberrant NFAT1 activation in resting T cells, and suggest that maintaining this pool of active SFKs in therapeutic T cells may increase the efficacy of T cell therapies.

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

    Directory of Open Access Journals (Sweden)

    Isabela Rodrigues Nogueira Forti

    Full Text Available 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 (P<0.001. In Brazil, the most frequent eye colour brown was significantly less frequent than expected in comparison to the general Brazilian 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.

  19. Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells.

    Science.gov (United States)

    Fonseca, Sonya G; Ishigaki, Shinsuke; Oslowski, Christine M; Lu, Simin; Lipson, Kathryn L; Ghosh, Rajarshi; Hayashi, Emiko; Ishihara, Hisamitsu; Oka, Yoshitomo; Permutt, M Alan; Urano, Fumihiko

    2010-03-01

    Wolfram syndrome is an autosomal-recessive disorder characterized by insulin-dependent diabetes mellitus, caused by nonautoimmune loss of beta cells, and neurological dysfunctions. We have previously shown that mutations in the Wolfram syndrome 1 (WFS1) gene cause Wolfram syndrome and that WFS1 has a protective function against ER stress. However, it remained to be determined how WFS1 mitigates ER stress. Here we have shown in rodent and human cell lines that WFS1 negatively regulates a key transcription factor involved in ER stress signaling, activating transcription factor 6alpha (ATF6alpha), through the ubiquitin-proteasome pathway. WFS1 suppressed expression of ATF6alpha target genes and repressed ATF6alpha-mediated activation of the ER stress response element (ERSE) promoter. Moreover, WFS1 stabilized the E3 ubiquitin ligase HRD1, brought ATF6alpha to the proteasome, and enhanced its ubiquitination and proteasome-mediated degradation, leading to suppression of ER stress signaling. Consistent with these data, beta cells from WFS1-deficient mice and lymphocytes from patients with Wolfram syndrome exhibited dysregulated ER stress signaling through upregulation of ATF6alpha and downregulation of HRD1. These results reveal a role for WFS1 in the negative regulation of ER stress signaling and in the pathogenesis of diseases involving chronic, unresolvable ER stress, such as pancreatic beta cell death in diabetes.

  20. β-arrestins negatively control human adrenomedullin type 1-receptor internalization

    International Nuclear Information System (INIS)

    Kuwasako, Kenji; Kitamura, Kazuo; Nagata, Sayaka; Sekiguchi, Toshio; Danfeng, Jiang; Murakami, Manabu; Hattori, Yuichi; Kato, Johji

    2017-01-01

    Adrenomedullin (AM) is a potent hypotensive peptide that exerts a powerful variety of protective effects against multiorgan damage through the AM type 1 receptor (AM 1 receptor), which consists of the calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 2 (RAMP2). Two β-arrestin (β-arr) isoforms, β-arr-1 and β-arr-2, play a central role in the agonist-induced internalization of many receptors for receptor resensitization. Notably, β-arr-biased agonists are now being tested in phase II clinical trials, targeting acute pain and acute heart failure. Here, we examined the effects of β-arr-1 and β-arr-2 on human AM 1 receptor internalization. We constructed a V5-tagged chimera in which the cytoplasmic C-terminal tail (C-tail) of CLR was replaced with that of the β 2 -adrenergic receptor (β 2 -AR), and it was transiently transfected into HEK-293 cells that stably expressed RAMP2. The cell-surface expression and internalization of the wild-type or chimeric receptor were quantified by flow cytometric analysis. The [ 125 I]AM binding and the AM-induced cAMP production of these receptors were also determined. Surprisingly, the coexpression of β-arr-1 or -2 resulted in significant decreases in AM 1 receptor internalization without affecting AM binding and signaling prior to receptor internalization. Dominant-negative (DN) β-arr-1 or -2 also significantly decreased AM-induced AM 1 receptor internalization. In contrast, the AM-induced internalization of the chimeric AM 1 receptor was markedly augmented by the cotransfection of β-arr-1 or -2 and significantly reduced by the coexpression of DN-β-arr-1 or -2. These results were consistent with those seen for β 2 -AR. Thus, both β-arrs negatively control AM 1 receptor internalization, which depends on the C-tail of CLR. - Highlights: • We found that β-arrestins 1 and 2 negatively control agonist-induced GPCR internalization. • β-arrestins 1 and 2 significantly inhibits the AM

  1. 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.

  2. 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.

  3. Osteocalcin as a negative regulator of serum leptin concentration in humans: insight from triathlon competitions.

    Science.gov (United States)

    Guadalupe-Grau, Amelia; Ara, Ignacio; Dorado, Cecilia; Vicente-Rodríguez, German; Perez-Gomez, Jorge; Cabrero, Javier Chavarren; Serrano-Sanchez, José A; Santana, Alfredo; Calbet, Jose A L

    2010-10-01

    Osteocalcin is a hormone produced by osteoblasts which acts as a negative regulator of fat mass, protecting against diet induced obesity and insulin resistance in rodents. To determine if an acute increase in osteocalcin concentration is associated with opposed changes in circulating leptin levels and insulin resistance we studied 15 middle and long distance male triathletes, (age 32.1 ± 6.9 years), before and 48 h after an Olympic (OT) or an Ironman (IT) triathlon competition. Muscle power, anaerobic capacity, body composition (dual-energy X-ray absorptiometry), and serum concentrations of testosterone, dihydrotestosterone, osteocalcin, leptin, glucose, insulin and insulin resistance (HOMA) were determined pre- and post-race. Pre- and 48 h post-race total and regional lean body mass was not altered, but fat mass was similarly increased (~250 g) 48 h after the competitions. This elicited an increase in plasma leptin of 33% after the IT while it remained unchanged after the OT, likely due to a 25% increase in plasma osteocalcin which occurred only after the OT (all p < 0.05). Post-race HOMA remained unchanged in OT and IT. Performance was normalized 48 h after the competitions, with the exception of a slightly lower jumping capacity after the IT. Serum testosterone concentration tended to decrease by 10% after the IT whilst dihydrotestosterone was reduced by 24% after the IT. In conclusion, an acute increase in serum osteocalcin concentration blunts the expected increase of serum leptin concentration that should occur with fat mass gain. This study provides evidence for osteocalcin as a negative regulator of serum leptin in humans.

  4. 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 oral sex (from 25% to 80%; P oral sex, regardless of tumor HPV status. 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.

  5. Non-Negative Tensor Factorization for Human Behavioral Pattern Mining in Online Games

    Directory of Open Access Journals (Sweden)

    Anna Sapienza

    2018-03-01

    Full Text Available Multiplayer online battle arena is a genre of online games that has become extremely popular. Due to their success, these games also drew the attention of our research community, because they provide a wealth of information about human online interactions and behaviors. A crucial problem is the extraction of activity patterns that characterize this type of data, in an interpretable way. Here, we leverage the Non-negative Tensor Factorization to detect hidden correlated behaviors of playing in a well-known game: League of Legends. To this aim, we collect the entire gaming history of a group of about 1000 players, which accounts for roughly 100K matches. By applying our framework we are able to separate players into different groups. We show that each group exhibits similar features and playing strategies, as well as similar temporal trajectories, i.e., behavioral progressions over the course of their gaming history. We surprisingly discover that playing strategies are stable over time and we provide an explanation for this observation.

  6. 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.

  7. Keratin 17 is overexpressed and predicts poor survival in estrogen receptor-negative/human epidermal growth factor receptor-2-negative breast cancer.

    Science.gov (United States)

    Merkin, Ross D; Vanner, Elizabeth A; Romeiser, Jamie L; Shroyer, A Laurie W; Escobar-Hoyos, Luisa F; Li, Jinyu; Powers, Robert S; Burke, Stephanie; Shroyer, Kenneth R

    2017-04-01

    Clinicopathological features of breast cancer have limited accuracy to predict survival. By immunohistochemistry (IHC), keratin 17 (K17) expression has been correlated with triple-negative status (estrogen receptor [ER]/progesterone receptor/human epidermal growth factor receptor-2 [HER2] negative) and decreased survival, but K17 messenger RNA (mRNA) expression has not been evaluated in breast cancer. K17 is a potential prognostic cancer biomarker, targeting p27, and driving cell cycle progression. This study compared K17 protein and mRNA expression to ER/progesterone receptor/HER2 receptor status and event-free survival. K17 IHC was performed on 164 invasive breast cancers and K17 mRNA was evaluated in 1097 breast cancers. The mRNA status of other keratins (16/14/9) was evaluated in 113 ER - /HER2 - ductal carcinomas. IHC demonstrated intense cytoplasmic and membranous K17 localization in myoepithelial cells of benign ducts and lobules and tumor cells of ductal carcinoma in situ. In ductal carcinomas, K17 protein was detected in most triple-negative tumors (28/34, 82%), some non-triple-negative tumors (52/112, 46%), but never in lobular carcinomas (0/15). In ductal carcinomas, high K17 mRNA was associated with reduced 5-year event-free survival in advanced tumor stage (n = 149, hazard ratio [HR] = 3.68, P = .018), and large (n = 73, HR = 3.95, P = .047), triple-negative (n = 103, HR = 2.73, P = .073), and ER - /HER2 - (n = 113, HR = 2.99, P = .049) tumors. There were significant correlations among keratins 17, 16, 14, and 9 mRNA levels suggesting these keratins (all encoded on chromosome 17) could be coordinately expressed in breast cancer. Thus, K17 is expressed in a subset of triple-negative breast cancers, and is a marker of poor prognosis in patients with advanced stage and ER - /HER2 - breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Human Polycomb group EED protein negatively affects HIV-1 assembly and release

    Directory of Open Access Journals (Sweden)

    Darlix Jean-Luc

    2007-06-01

    Full Text Available Abstract Background The human EED protein, a member of the superfamily of Polycomb group (PcG proteins with WD-40 repeats, has been found to interact with three HIV-1 components, namely the structural Gag matrix protein (MA, the integrase enzyme (IN and the Nef protein. The aim of the present study was to analyze the possible biological role of EED in HIV-1 replication, using the HIV-1-based vector HIV-Luc and EED protein expressed by DNA transfection of 293T cells. Results During the early phase of HIV-1 infection, a slight negative effect on virus infectivity occurred in EED-expressing cells, which appeared to be dependent on EED-MA interaction. At late times post infection, EED caused an important reduction of virus production, from 20- to 25-fold as determined by CAp24 immunoassay, to 10- to 80-fold based on genomic RNA levels, and this decrease was not due to a reduction of Gag protein synthesis. Coexpression of WTNef, or the non-N-myristoylated mutant NefG2A, restored virus yields to levels obtained in the absence of exogenous EED protein. This effect was not observed with mutant NefΔ57 mimicking the Nef core, or with the lipid raft-retargeted fusion protein LAT-Nef. LATAA-Nef, a mutant defective in the lipid raft addressing function, had the same anti-EED effect as WTNef. Cell fractionation and confocal imaging showed that, in the absence of Nef, EED mainly localized in membrane domains different from the lipid rafts. Upon co-expression with WTNef, NefG2A or LATAA-Nef, but not with NefΔ57 or LAT-Nef, EED was found to relocate into an insoluble fraction along with Nef protein. Electron microscopy of HIV-Luc producer cells overexpressing EED showed significant less virus budding at the cell surface compared to control cells, and ectopic assembly and clustering of nuclear pore complexes within the cytoplasm. Conclusion Our data suggested that EED exerted an antiviral activity at the late stage of HIV-1 replication, which included genomic

  9. β-arrestins negatively control human adrenomedullin type 1-receptor internalization.

    Science.gov (United States)

    Kuwasako, Kenji; Kitamura, Kazuo; Nagata, Sayaka; Sekiguchi, Toshio; Danfeng, Jiang; Murakami, Manabu; Hattori, Yuichi; Kato, Johji

    2017-05-27

    Adrenomedullin (AM) is a potent hypotensive peptide that exerts a powerful variety of protective effects against multiorgan damage through the AM type 1 receptor (AM 1 receptor), which consists of the calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 2 (RAMP2). Two β-arrestin (β-arr) isoforms, β-arr-1 and β-arr-2, play a central role in the agonist-induced internalization of many receptors for receptor resensitization. Notably, β-arr-biased agonists are now being tested in phase II clinical trials, targeting acute pain and acute heart failure. Here, we examined the effects of β-arr-1 and β-arr-2 on human AM 1 receptor internalization. We constructed a V5-tagged chimera in which the cytoplasmic C-terminal tail (C-tail) of CLR was replaced with that of the β 2 -adrenergic receptor (β 2 -AR), and it was transiently transfected into HEK-293 cells that stably expressed RAMP2. The cell-surface expression and internalization of the wild-type or chimeric receptor were quantified by flow cytometric analysis. The [ 125 I]AM binding and the AM-induced cAMP production of these receptors were also determined. Surprisingly, the coexpression of β-arr-1 or -2 resulted in significant decreases in AM 1 receptor internalization without affecting AM binding and signaling prior to receptor internalization. Dominant-negative (DN) β-arr-1 or -2 also significantly decreased AM-induced AM 1 receptor internalization. In contrast, the AM-induced internalization of the chimeric AM 1 receptor was markedly augmented by the cotransfection of β-arr-1 or -2 and significantly reduced by the coexpression of DN-β-arr-1 or -2. These results were consistent with those seen for β 2 -AR. Thus, both β-arrs negatively control AM 1 receptor internalization, which depends on the C-tail of CLR. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. 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

  11. 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.

  12. 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 m...

  13. Septicemia caused by the gram-negative bacterium CDC IV c-2 in an immunocompromised human.

    OpenAIRE

    Dan, M; Berger, S A; Aderka, D; Levo, Y

    1986-01-01

    A 37-year-old man with plasma cell leukemia developed nonfatal septicemia caused by the gram-negative bacterium CDC IV c-2. Recovery followed appropriate treatment with antibiotics. The biochemical features of this organism are reviewed.

  14. Paradigms for Assessing Hedonic Processing and Motivation in Humans: Relevance to Understanding Negative Symptoms in Psychopathology.

    Science.gov (United States)

    Barch, Deanna M; Gold, James M; Kring, Ann M

    2017-07-01

    Clinicians and researchers have long known that one of the debilitating aspects of psychotic disorders is the presence of "negative symptoms," which involve impairments in hedonic and motivational function, and/or alterations in expressive affect. We have a number of excellent clinical tools available for assessing the presence and severity of negative symptoms. However, to better understand the mechanisms that may give rise to negative symptoms, we need tools and methods that can help distinguish among different potential contributing causes, as a means to develop more targeted intervention pathways. Using such paradigms is particularly important if we wish to understand whether the causes are the same or different across disorders that may share surface features of negative symptoms. This approach is in line with the goals of the Research Diagnostic Criteria Initiative, which advocates understanding the nature of core dimensions of brain-behavior relationships transdiagnostically. Here we highlight some of the emerging measures and paradigms that may help us to parse the nature and causes of negative symptoms, illustrating both the research approaches from which they emerge and the types of constructs that they can help elucidate. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. Molecular dynamics study of the dominant-negative E219K polymorphism in human prion protein

    NARCIS (Netherlands)

    Jahandideh, Samad; Jamalan, Mostafa; Faridounnia, Maryam|info:eu-repo/dai/nl/338666923

    2015-01-01

    Human prion diseases are associated with misfolding or aggregation of the Human Prion Protein (HuPrP). Missense mutations in the HuPrP gene, contribute to conversion of HuPrP(C) to HuPrP(Sc) and amyloid formation. Based on our previous comprehensive study, three missense mutations, from two

  16. 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…

  17. Positive and negative social support and HPA-axis hyperactivity: Evidence from glucocorticoids in human hair.

    Science.gov (United States)

    Iob, Eleonora; Kirschbaum, Clemens; Steptoe, Andrew

    2018-06-12

    While positive social support is associated with lower prevalence of disease and better treatment outcomes, negative social relationships can instead have unfavourable consequences for several physical and mental health conditions. However, the specific mechanisms by which this nexus might operate remain poorly understood. Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity owing to psychosocial stress has been proposed as a potential pathway underlying the link between social support and health. Hair glucocorticoids such as cortisol and cortisone are emerging as promising biomarkers of long-term retrospective HPA activation. Therefore, the aim of this investigation was to examine the effects of positive and negative experiences of social support within key relationships (i.e. spouse/partner, children, other family members, and friends) on cortisol and cortisone. These associations were tested in a sample of 2520 older adults (mean age 68.1) from the English Longitudinal Study of Ageing. Hair samples were collected in wave 6 (2012/13). To understand the impact of cumulative exposure to poor social support, the analysis used self-reported data from waves 4 (2008/09) and 6. Covariates included demographic, socioeconomic, lifestyle, and hair characteristics. In cross sectional analyses, lower positive support from all sources and specifically from children were associated with higher cortisol. Additionally, lower positive support from children was positively associated with cortisone. Similarly, higher overall negative support was related to higher cortisol, and greater negative support from children was also positively associated with cortisone. In longitudinal analyses, there was evidence for positive associations between hair glucocorticoids and cumulative exposure to poorer social support. Experiences of low positive and high negative social support, particularly from children, were both related to higher hair glucocorticoids. Hence, social relationships of

  18. 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.

  19. 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.

  20. Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons

    OpenAIRE

    Morelli, Annamaria; Comeglio, Paolo; Sarchielli, Erica; Cellai, Ilaria; Vignozzi, Linda; Vannelli, Gabriella B.; Maggi, Mario

    2013-01-01

    Metabolic disorders are often associated with male hypogonadotropic hypogonadism, suggesting that hypothalamic defects involving GnRH neurons may impair the reproductive function. Among metabolic factors hyperglycemia has been implicated in the control of the reproductive axis at central level, both in humans and in animal models. To date, little is known about the direct effects of pathological high glucose concentrations on human GnRH neurons. In this study, we investigated the high glucose...

  1. 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.

  2. Incidence, adherence, and antibiotic resistance of coagulase-negative Staphylococcus species causing human disease.

    Science.gov (United States)

    Needham, C A; Stempsey, W

    1984-09-01

    Fifty-two isolates of coagulase-negative Staphylococcus species recovered from the blood or intravenous catheters of patients with clinically significant disease were compared to 60 similar isolates from patients who were presumably colonized. All isolates were identified and evaluated for ability to adhere to smooth surfaces, and resistance to anti-staphylococcal penicillins. S. epidermidis, S. hominis, and S. haemolyticus were the most frequently occurring species, representing 65%, 15%, and 10%, respectively, of disease isolates and 57%, 25%, and 8% of colonizers. The seven other species recovered accounted for only 10% of the total in both groups. Differences in isolation rates of each species within the two groups were not significant and were reflective of their reported incidence in the normal flora. All species of coagulase-negative Staphylococcus (except S. capitis and S. cohnii, which were isolated in very small numbers) were capable of adhering to smooth surfaces. S. hominis disease isolates were all capable of adherence, and the difference between the disease isolates and colonizers was statistically significant (p less than 0.02). This was not true for any other species that was analyzed nor for all isolates considered as a whole. Resistance to anti-staphylococcal penicillins was documented for all coagulase-negative Staphylococcus species, and was more frequent in S. epidermidis disease isolates than colonizers (p less than 0.05). No correlation was found between resistance to antistaphylococcal penicillins and ability to adhere.

  3. 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, Prelation to HPV 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

  4. Characterization of the positive and negative inotropic effects of acetylcholine in the human myocardium

    NARCIS (Netherlands)

    X.Y. Du (Xiaoyi); R.G. Schoemaker (Regien); E. Bos (Egbert); P.R. Saxena (Pramod Ranjan)

    1995-01-01

    textabstractIn the human isolated myocardium, acetylcholine (10−9 to 10−3 M) elicited a biphasic inotropic effect (a decrease in the lower and an increase in the higher concentration range) in atrial and a positive inotropic effect in ventricular trabeculae. However, under conditions of raised

  5. 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

  6. Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons

    Directory of Open Access Journals (Sweden)

    Annamaria Morelli

    2013-01-01

    Full Text Available Metabolic disorders are often associated with male hypogonadotropic hypogonadism, suggesting that hypothalamic defects involving GnRH neurons may impair the reproductive function. Among metabolic factors hyperglycemia has been implicated in the control of the reproductive axis at central level, both in humans and in animal models. To date, little is known about the direct effects of pathological high glucose concentrations on human GnRH neurons. In this study, we investigated the high glucose effects in the human GnRH-secreting FNC-B4 cells. Gene expression profiling by qRT-PCR, confirmed that FNC-B4 cells express GnRH and several genes relevant for GnRH neuron function (KISS1R, KISS1, sex steroid and leptin receptors, FGFR1, neuropilin 2, and semaphorins, along with glucose transporters (GLUT1, GLUT3, and GLUT4. High glucose exposure (22 mM; 40 mM significantly reduced gene and protein expression of GnRH, KISS1R, KISS1, and leptin receptor, as compared to normal glucose (5 mM. Consistent with previous studies, leptin treatment significantly induced GnRH mRNA expression at 5 mM glucose, but not in the presence of high glucose concentrations. In conclusion, our findings demonstrate a deleterious direct contribution of high glucose on human GnRH neurons, thus providing new insights into pathogenic mechanisms linking metabolic disorders to reproductive dysfunctions.

  7. Direct labelling of the human P2X7 receptor and identification of positive and negative cooperativity of binding.

    Science.gov (United States)

    Michel, A D; Chambers, L J; Clay, W C; Condreay, J P; Walter, D S; Chessell, I P

    2007-05-01

    The P2X(7) receptor exhibits complex pharmacological properties. In this study, binding of a [(3)H]-labelled P2X(7) receptor antagonist to human P2X(7) receptors has been examined to further understand ligand interactions with this receptor. The P2X(7) receptor antagonist, N-[2-({2-[(2-hydroxyethyl)amino]ethyl}amino)-5-quinolinyl]-2-tricyclo[3.3.1.1(3,7)]dec-1-ylacetamide (compound-17), was radiolabelled with tritium and binding studies were performed using membranes prepared from U-2 OS or HEK293 cells expressing human recombinant P2X(7) receptors. Binding of [(3)H]-compound-17 was higher in membranes prepared from cells expressing P2X(7) receptors than from control cells and was inhibited by ATP suggesting labelled sites represented human P2X(7) receptors. Binding was reversible, saturable and modulated by P2X(7) receptor ligands (Brilliant Blue G, KN62, ATP, decavanadate). Furthermore, ATP potency was reduced in the presence of divalent cations or NaCl. Radioligand binding exhibited both positive and negative cooperativity. Positive cooperativity was evident from bell shaped Scatchard plots, reduction in radioligand dissociation rate by unlabelled compound-17 and enhancement of radioligand binding by KN62 and unlabelled compound-17. ATP and decavanadate inhibited binding in a negative cooperative manner as they enhanced radioligand dissociation. These data demonstrate that human P2X(7) receptors can be directly labelled and provide novel insights into receptor function. The positive cooperativity observed suggests that binding of compound-17 to one subunit in the P2X(7) receptor complex enhances subsequent binding to other P2X(7) subunits in the same complex. The negative cooperative effects of ATP suggest that ATP and compound-17 bind at separate, interacting, sites on the P2X(7) receptor.

  8. 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.

  9. Cfr-mediated linezolid-resistance among methicillin-resistant coagulase-negative staphylococci from infections of humans.

    Directory of Open Access Journals (Sweden)

    Lanqing Cui

    Full Text Available Four methicillin-resistant coagulase-negative staphylococci (MRCoNS, one Staphylococcus haemolyticus and three Staphylococcus cohnii, from infections of humans collected via the Ministry of Health National Antimicrobial Resistance Surveillance Net (Mohnarin program in China were identified as linezolid-resistant. These four isolates were negative for the 23S rRNA mutations, but positive for the gene cfr. Mutations in the gene for the ribosomal protein L3, which resulted in the amino acid exchanges Gly152Asp and Tyr158Phe, were identified in S. haemolyticus 09D279 and S. cohnii NDM113, respectively. In each isolate, the cfr gene was located on a plasmid of ca. 35.4 kb, as shown by S1 nuclease pulsed-field gel electrophoresis and Southern blotting experiments. This plasmid was indistinguishable from the previously described plasmid pSS-02 by its size, restriction pattern, and a sequenced 14-kb cfr-carrying segment. Plasmid pSS-02 was originally identified in staphylococci isolated from pigs. This is the first time that a cfr-carrying plasmid has been detected in MRCoNS obtained from intensive care patients in China. Based on the similarities to the cfr-carrying plasmid pSS-02 from porcine coagulase-negative staphylococci, a transmission of this cfr-carrying plasmid between staphylococci from pigs and humans appears to be likely.

  10. Cfr-mediated linezolid-resistance among methicillin-resistant coagulase-negative staphylococci from infections of humans.

    Science.gov (United States)

    Cui, Lanqing; Wang, Yang; Li, Yun; He, Tao; Schwarz, Stefan; Ding, Yujing; Shen, Jianzhong; Lv, Yuan

    2013-01-01

    Four methicillin-resistant coagulase-negative staphylococci (MRCoNS), one Staphylococcus haemolyticus and three Staphylococcus cohnii, from infections of humans collected via the Ministry of Health National Antimicrobial Resistance Surveillance Net (Mohnarin) program in China were identified as linezolid-resistant. These four isolates were negative for the 23S rRNA mutations, but positive for the gene cfr. Mutations in the gene for the ribosomal protein L3, which resulted in the amino acid exchanges Gly152Asp and Tyr158Phe, were identified in S. haemolyticus 09D279 and S. cohnii NDM113, respectively. In each isolate, the cfr gene was located on a plasmid of ca. 35.4 kb, as shown by S1 nuclease pulsed-field gel electrophoresis and Southern blotting experiments. This plasmid was indistinguishable from the previously described plasmid pSS-02 by its size, restriction pattern, and a sequenced 14-kb cfr-carrying segment. Plasmid pSS-02 was originally identified in staphylococci isolated from pigs. This is the first time that a cfr-carrying plasmid has been detected in MRCoNS obtained from intensive care patients in China. Based on the similarities to the cfr-carrying plasmid pSS-02 from porcine coagulase-negative staphylococci, a transmission of this cfr-carrying plasmid between staphylococci from pigs and humans appears to be likely.

  11. Metastatic MHC class I-negative mouse cells derived by transformation with human papillomavirus type 16

    Czech Academy of Sciences Publication Activity Database

    Šmahel, M.; Sobotková, E.; Bubeník, Jan; Šímová, Jana; Žák, R.; Ludvíková, V.; Mikyšková, Romana; Kovařík, J.; Jelínek, F.; Povýšil, C.; Marinov, J.; Vonka, V.

    2001-01-01

    Roč. 84, č. 3 (2001), s. 374-380 ISSN 0007-0920 R&D Projects: GA MZd NC5900; GA MZd NC5526; GA ČR GA312/99/0542; GA ČR GA312/98/0826 Institutional research plan: CEZ:AV0Z5052915 Keywords : human papillomavirus * E6/E7 oncogenes * cell transformation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.942, year: 2001

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

    Science.gov (United States)

    2016-09-01

    behaviors believed responsible for these actions. The final category of inefficient energy behaviors analyzed is vehicle use. Vehicles consume 70...transitions to a summary of collected data that includes where energy is consumed and inefficient uses resulting from human behavior . The data is...tropical areas of Southeast Asia were gathered that captured the employment of energy producing and consuming devices as well as related user behaviors

  13. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chennubhotla, Chakra [University of Pittsburgh School of Medicine, Pittsburgh PA; Castro, Jason [Bates College

    2013-01-01

    In contrast to most other sensory modalities, the basic perceptual dimensions of olfaction remain un- clear. 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 di- mensions 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.

  15. 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.

  16. 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

  17. Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

    Directory of Open Access Journals (Sweden)

    Hongzhe Li

    2014-12-01

    Full Text Available Human bone marrow (BM contains a rare population of nonhematopoietic mesenchymal stromal cells (MSCs, which are of central importance for the hematopoietic microenvironment. However, the precise phenotypic definition of these cells in adult BM has not yet been reported. In this study, we show that low/negative expression of CD140a (PDGFR-α on lin−/CD45−/CD271+ BM cells identified a cell population with very high MSC activity, measured as fibroblastic colony-forming unit frequency and typical in vitro and in vivo stroma formation and differentiation capacities. Furthermore, these cells exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin−/CD45−/CD271+/CD140alow/− cells effectively mediated the ex vivo expansion of transplantable CD34+ hematopoietic stem cells. Taken together, these data indicate that CD140a is a key negative selection marker for adult human BM-MSCs, which enables to prospectively isolate a close to pure population of candidate human adult stroma stem/progenitor cells with potent hematopoiesis-supporting capacity.

  18. Sperm competition in humans: mate guarding behavior negatively correlates with ejaculate quality.

    Science.gov (United States)

    Leivers, Samantha; Rhodes, Gillian; Simmons, Leigh W

    2014-01-01

    In species where females mate with multiple males, the sperm from these males must compete to fertilise available ova. Sexual selection from sperm competition is expected to favor opposing adaptations in males that function either in the avoidance of sperm competition (by guarding females from rival males) or in the engagement in sperm competition (by increased expenditure on the ejaculate). The extent to which males may adjust the relative use of these opposing tactics has been relatively neglected. Where males can successfully avoid sperm competition from rivals, one might expect a decrease in their expenditure on tactics for the engagement in sperm competition and vice versa. In this study, we examine the relationship between mate guarding and ejaculate quality using humans as an empirical model. We found that men who performed fewer mate guarding behaviors produced higher quality ejaculates, having a greater concentration of sperm, a higher percentage of motile sperm and sperm that swam faster and less erratically. These effects were found independent of lifestyle factors or factors related to male quality. Our findings suggest that male expenditure on mate guarding and on the ejaculate may represent alternative routes to paternity assurance in humans.

  19. 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."

  20. 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...... volunteers before and after atropine administration. LBNP of 55 mmHg initially resulted in an increase in HR from 55 +/- 4 to 90 +/- 5 beats/min and decreases in mean arterial pressure (MAP) from 94 +/- 4 to 81 +/- 5 mmHg, in central venous pressure from 7 +/- 1 to -3 +/- 1 mmHg, and in cardiac output from 6.......1 +/- 0.5 to 3.7 +/- 0.11/min. Concomitantly, epinephrine and norepinephrine levels increased. After 8.2 +/- 2.3 min of LBNP, the MAP had decreased to 41 +/- 7 mmHg and HR had decreased to 57 +/- 3 beats/min. Vasopressin increased from 1.2 +/- 0.3 to 137 +/- 45 pg/ml and renin activity increased from 1...

  1. 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

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

    Science.gov (United States)

    Liu, Yadong; Shen, Hui; Zhou, Zongtan; Hu, Dewen

    2011-01-01

    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."

  3. Hepatic glucose output in humans measured with labeled glucose to reduce negative errors

    International Nuclear Information System (INIS)

    Levy, J.C.; Brown, G.; Matthews, D.R.; Turner, R.C.

    1989-01-01

    Steele and others have suggested that minimizing changes in glucose specific activity when estimating hepatic glucose output (HGO) during glucose infusions could reduce non-steady-state errors. This approach was assessed in nondiabetic and type II diabetic subjects during constant low dose [27 mumol.kg ideal body wt (IBW)-1.min-1] glucose infusion followed by a 12 mmol/l hyperglycemic clamp. Eight subjects had paired tests with and without labeled infusions. Labeled infusion was used to compare HGO in 11 nondiabetic and 15 diabetic subjects. Whereas unlabeled infusions produced negative values for endogenous glucose output, labeled infusions largely eliminated this error and reduced the dependence of the Steele model on the pool fraction in the paired tests. By use of labeled infusions, 11 nondiabetic subjects suppressed HGO from 10.2 +/- 0.6 (SE) fasting to 0.8 +/- 0.9 mumol.kg IBW-1.min-1 after 90 min of glucose infusion and to -1.9 +/- 0.5 mumol.kg IBW-1.min-1 after 90 min of a 12 mmol/l glucose clamp, but 15 diabetic subjects suppressed only partially from 13.0 +/- 0.9 fasting to 5.7 +/- 1.2 at the end of the glucose infusion and 5.6 +/- 1.0 mumol.kg IBW-1.min-1 in the clamp (P = 0.02, 0.002, and less than 0.001, respectively)

  4. A nomogram for predicting pathological complete response in patients with human epidermal growth factor receptor 2 negative breast cancer

    International Nuclear Information System (INIS)

    Jin, Xi; Jiang, Yi-Zhou; Chen, Sheng; Yu, Ke-Da; Ma, Ding; Sun, Wei; Shao, Zhi-Min; Di, Gen-Hong

    2016-01-01

    The response to neoadjuvant chemotherapy has been proven to predict long-term clinical benefits for patients. Our research is to construct a nomogram to predict pathological complete response of human epidermal growth factor receptor 2 negative breast cancer patients. We enrolled 815 patients who received neoadjuvant chemotherapy from 2003 to 2015 and divided them into a training set and a validation set. Univariate logistic regression was performed to screen for predictors and construct the nomogram; multivariate logistic regression was performed to identify independent predictors. After performing the univariate logistic regression analysis in the training set, tumor size, hormone receptor status, regimens of neoadjuvant chemotherapy and cycles of neoadjuvant chemotherapy were the final predictors for the construction of the nomogram. The multivariate logistic regression analysis demonstrated that T4 status, hormone receptor status and receiving regimen of paclitaxel and carboplatin were independent predictors of pathological complete response. The area under the receiver operating characteristic curve of the training set and the validation set was 0.779 and 0.701, respectively. We constructed and validated a nomogram to predict pathological complete response in human epidermal growth factor receptor 2 negative breast cancer patients. We also identified tumor size, hormone receptor status and paclitaxel and carboplatin regimen as independent predictors of pathological complete response. The online version of this article (doi:10.1186/s12885-016-2652-z) contains supplementary material, which is available to authorized users

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

    Science.gov (United States)

    Choi, Hyunjung; Shin, Ji Hyun; Kim, Eun Sung; Park, So Jung; Bae, Il-Hong; Jo, Yoon Kyung; Jeong, In Young; Kim, Hyoung-June; Lee, Youngjin; Park, Hea Chul; Jeon, Hong Bae; Kim, Ki Woo; Lee, Tae Ryong; Cho, Dong-Hyung

    2016-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Impact of chemical peeling combined with negative pressure on human skin.

    Science.gov (United States)

    Kim, S J; Kang, I J; Shin, M K; Jeong, K H; Baek, J H; Koh, J S; Lee, S J

    2016-10-01

    In vivo changes in skin barrier function after chemical peeling with alpha hydroxyacids (AHAs) have been previously reported. However, the additional effects of physical treatment with chemical agents on skin barrier function have not been adequately studied. This study measured the degree of acute skin damage and the time required for skin barrier repair using non-invasive bioengineering methods in vivo with human skin to investigate the additional effect of a 4% AHA chemical jet accelerated at supersonic velocities. Thirteen female subjects (average age: 29.54 ± 4.86 years) participated in this study. The faces of the subjects were divided into half according to the block randomization design and were then assigned to receive AHA peeling alone or AHA peeling combined with pneumatic pressure on each side of the face. Transepidermal water loss (TEWL), skin colour and skin blood flow were evaluated at baseline and at 30 min, 2, 5 and 7 days after treatment. The TEWL and skin blood flow were significantly increased after 30 min in chemodermabrasion compared with chemical peeling alone (P peeling alone (P < 0.05). Chemodermabrasion can temporarily impair skin barriers, but it is estimated that it can enhance the skin barrier function after 7 days compared to the use of a chemical agent alone. In addition, chemodermabrasion has a more effective impact in the dermis and relatively preserves the skin barrier. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  8. Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

    DEFF Research Database (Denmark)

    Li, Hongzhe; Ghazanfari, Roshanak; Zacharaki, Dimitra

    2014-01-01

    Human bone marrow (BM) contains a rare population of nonhematopoietic mesenchymal stromal cells (MSCs), which are of central importance for the hematopoietic microenvironment. However, the precise phenotypic definition of these cells in adult BM has not yet been reported. In this study, we show...... exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin(-)/CD45(-)/CD271(+)/CD140a(low/-) cells effectively mediated the ex vivo expansion of transplantable CD34(+) hematopoietic stem cells. Taken together, these data indicate that CD140a is a key...... that low/negative expression of CD140a (PDGFR-α) on lin(-)/CD45(-)/CD271(+) BM cells identified a cell population with very high MSC activity, measured as fibroblastic colony-forming unit frequency and typical in vitro and in vivo stroma formation and differentiation capacities. Furthermore, these cells...

  9. 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

    Fetal antigen 1 (FA1) is a glycoprotein containing six epidermal growth factor (EGF)-like repeats. It is closely similar to the protein translated from the human delta-like (dlk) cDNA and probably constitutes a proteolytically processed form of dlk. dlk is homologous to the Drosophila homeotic...... proteins delta and notch and to the murine preadipocyte differentiation factor Pref-1. These proteins participate in determining cell fate choices during differentiation. We now report that FA1 immunoreactivity is present in a number of neuroectodermally derived tumours as well as in pancreatic endocrine...... 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...

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

    International Nuclear Information System (INIS)

    Baek, Hye Jin; Kim, Woo Jin

    2013-01-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    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. Androgen receptor-negative human prostate cancer cells induce osteogenesis in mice through FGF9-mediated mechanisms.

    Science.gov (United States)

    Li, Zhi Gang; Mathew, Paul; Yang, Jun; Starbuck, Michael W; Zurita, Amado J; Liu, Jie; Sikes, Charles; Multani, Asha S; Efstathiou, Eleni; Lopez, Adriana; Wang, Jing; Fanning, Tina V; Prieto, Victor G; Kundra, Vikas; Vazquez, Elba S; Troncoso, Patricia; Raymond, Austin K; Logothetis, Christopher J; Lin, Sue-Hwa; Maity, Sankar; Navone, Nora M

    2008-08-01

    In prostate cancer, androgen blockade strategies are commonly used to treat osteoblastic bone metastases. However, responses to these therapies are typically brief, and the mechanism underlying androgen-independent progression is not clear. Here, we established what we believe to be the first human androgen receptor-negative prostate cancer xenografts whose cells induced an osteoblastic reaction in bone and in the subcutis of immunodeficient mice. Accordingly, these cells grew in castrated as well as intact male mice. We identified FGF9 as being overexpressed in the xenografts relative to other bone-derived prostate cancer cells and discovered that FGF9 induced osteoblast proliferation and new bone formation in a bone organ assay. Mice treated with FGF9-neutralizing antibody developed smaller bone tumors and reduced bone formation. Finally, we found positive FGF9 immunostaining in prostate cancer cells in 24 of 56 primary tumors derived from human organ-confined prostate cancer and in 25 of 25 bone metastasis cases studied. Collectively, these results suggest that FGF9 contributes to prostate cancer-induced new bone formation and may participate in the osteoblastic progression of prostate cancer in bone. Androgen receptor-null cells may contribute to the castration-resistant osteoblastic progression of prostate cancer cells in bone and provide a preclinical model for studying therapies that target these cells.

  14. Negative feedback regulation of human platelets via autocrine activation of the platelet-derived growth factor alpha-receptor.

    Science.gov (United States)

    Vassbotn, F S; Havnen, O K; Heldin, C H; Holmsen, H

    1994-05-13

    Human platelets contain platelet-derived growth factor (PDGF) in their alpha-granules which is released during platelet exocytosis. We show by immunoprecipitation and 125I-PDGF binding experiments that human platelets have functionally active PDGF alpha-receptors, but not beta-receptors. The PDGF alpha-receptor (PDGFR-alpha) was identified as a 170-kDa glycosylated protein-tyrosine kinase as found in other cell types. Stimulation of platelets with 0.1 unit/ml thrombin resulted in a significant increase (2-5-fold) of the tyrosine phosphorylation of the PDGFR-alpha, as determined by immunoprecipitation with phosphotyrosine antiserum as well as with PDGFR-alpha antiserum. The observed thrombin-induced autophosphorylation of the PDGFR-alpha was inhibited by the addition of a neutralizing monoclonal PDGF antibody. Thus, our results suggest that the platelet PDGFR-alpha is stimulated in an autocrine manner by PDGF secreted during platelet activation. Preincubation of platelets with PDGF inhibited thrombin-induced platelet aggregation and secretion of ATP + ADP and beta-hexosaminidase. Thrombin-induced platelet aggregation was also reversed when PDGF was added 30 s after thrombin stimulation. Inhibition of the autocrine PDGF pathway during platelet activation by the PDGF antibody led to a potentiation of thrombin-induced beta-hexosaminidase secretion. Thus, the PDGFR-alpha takes part in a negative feedback regulation during platelet activation. Our demonstration of PDGF alpha-receptors on human platelets and its inhibitory function during platelet activation identifies a new possible role of PDGF in the regulation of thrombosis.

  15. The low risk of precancer after a screening result of human papillomavirus-negative/atypical squamous cells of undetermined significance papanicolaou and implications for clinical management.

    Science.gov (United States)

    Gage, Julia C; Katki, Hormuzd A; Schiffman, Mark; Castle, Philip E; Fetterman, Barbara; Poitras, Nancy E; Lorey, Thomas; Cheung, Li C; Behrens, Catherine; Sharma, Abha; Zhao, Fang-Hui; Cuzick, Jack; Yang, Zi Hua; Kinney, Walter K

    2014-11-01

    Different US practice guidelines have conflicting recommendations for when women should return after a screening result of human papillomavirus (HPV)-negative with an equivocal Papanicolaou (Pap) result of atypical squamous cells of undetermined significance (ASC-US) (ie, return in either 3 or 5 years). One way to determine management is to compare the risk of precancer/cancer after an HPV-negative/ASC-US result with the risks after other negative screening results. For example, if the risk after an HPV-negative/ASC-US result was similar to the risk after a negative Pap test, a 3-year return would be preferred because guidelines agree that women with negative Pap test results should return in 3 years. Alternatively, if the risk after an HPV-negative/ASC-US result is similar to that after a cotest-negative result (HPV negative/Pap test negative), a 5-year return would be preferred because guidelines agree that women testing cotest negative should return in 5 years. The authors compared risks of cervical intraepithelial neoplasia of grade 3 or higher (CIN3+) and cervical cancer among women aged 30 years to 64 years at Kaiser Permanente Northern California with the following test results from 2003 through 2012: 17,191 women testing HPV negative/ASC-US; 980,268 women testing Pap test negative (regardless of HPV result); and 892,882 women testing cotest negative. The 5-year CIN3+ and cancer risks after an HPV-negative/ASC-US result were closer to the risks after a negative Pap test result (CIN3+: 0.48% vs 0.31% [P =.0019]; and cancer: 0.043% vs 0.031% [P =.4]) than after a negative cotest (CIN3+: 0.48% vs 0.11% [P<.0001]; and cancer: 0.043% vs 0.014% [P =.016]). Women testing HPV negative/ASC-US were found to have precancer/cancer risks that were more closely aligned with women with negative Pap test results, suggesting that women testing HPV negative/ASC-US should be managed similarly to women testing negative on Pap tests with a 3-year return for screening. © 2014

  16. 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

    2016-01-01

    ABSTRACT 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-DRlo 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 blockade in the 4T1 mammary tumor model promoted maturation of MHCIIhi blood monocytes and TAMs and significantly reduced lung metastasis, anti-CSF-1R treatment promoted MHCIIloF4/80hiMRhi 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. PMID:27141367

  17. The distribution of sexually-transmitted Human Papillomaviruses in HIV positive and negative patients in Zambia, Africa

    Directory of Open Access Journals (Sweden)

    Hause Lara

    2007-07-01

    Full Text Available Abstract Background Human Papillomaviruses (HPV are double-stranded DNA viruses, considered to be the primary etiological agents in cervical intraepithelial neoplasias and cancers. Approximately 15–20 of the 40 mucosal HPVs confer a high-risk of progression of lesions to invasive cancer. In this study, we investigated the prevalence of sexually transmitted HPVs in Human Immunodeficiency Virus (HIV positive and negative patients in Zambia, Africa. The rate of high-risk HPV genotypes worldwide varies within each country. Thus, we sought to investigate the rates of HPV infection in sub-Saharan Africa and the potential role of HIV in affecting the HPV genotype distribution. Methods This retrospective cross-sectional study reports findings on the association and effects of HIV on HPV infections in an existing cohort of patients at University Teaching Hospital (UTH Lusaka, Zambia. The objective of this study was to assess HPV prevalence, genotype distribution and to identify co-factors that influence HPV infection. Polymerase chain reaction (PCR with two standard consensus primer sets (CpI/II and GP5+/6+ was used to test for the presence of HPV DNA. Primers specific for β-actin were used to monitor DNA quality. Vaginal lavage samples, collected between 1998-1999 from a total of 70 women, were part of a larger cohort that was also analyzed for HIV and human herpesvirus infection. Seventy of the samples yielded usable DNA. HIV status was determined by two rapid assays, Capillus and Determine. The incidence of HIV and HPV infections and HPV genotype distributions were calculated and statistical significance was determined by Chi-Squared test. Results We determined that most common HPV genotypes detected among these Zambian patients were types 16 and 18 (21.6% each, which is approximately three-fold greater than the rates for HPV16, and ten-fold greater than the rates for HPV18 in the United States. The worldwide prevalence of HPV16 is approximately 14

  18. 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

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

    International Nuclear Information System (INIS)

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

    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 the benefits of conversion due to increases in ozone (O 3 ) and fine particulate matter (PM 2.5 ) levels as a result of large changes in biogenic emissions. Using the Community Earth System Model we simulate the conversion of marginal and underutilized croplands worldwide to bioenergy crops under varying future anthropogenic emissions scenarios. A conservative global replacement using high VOC-emitting crop profiles leads to modeled population-weighted O 3 increases of 5–27 ppb in India, 1–9 ppb in China, and 1–6 ppb in the United States, with peak PM 2.5 increases of up to 2 μg m −3 . We present a metric for the regional evaluation of candidate bioenergy crops, as well as results for the application of this metric to four representative emissions profiles using four replacement scales (10–100% maximum estimated available land). Finally, we assess the total health and climate impacts of biogenic emissions, finding that the negative consequences of using high-emitting crops could exceed 50% of the positive benefits of reduced fossil fuel emissions in value. (letter)

  20. 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

  1. 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

  2. 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

  3. Early inhibitory effects of zoledronic acid in tooth extraction sockets in dogs are negated by recombinant human bone morphogenetic protein.

    Science.gov (United States)

    Gerard, David A; Carlson, Eric R; Gotcher, Jack E; Pickett, David O

    2014-01-01

    This study was conducted with 2 purposes. The first was to determine the effect of a single dose of zoledronic acid (ZA) on the healing of a tooth extraction socket in dogs. The second was to determine if placement of recombinant human bone morphogenetic protein-2 (rhBMP-2)/absorbable collagen sponge (ACS) - INFUSE, (Medtronic, Memphis, TN) into these extraction sockets would inhibit the inhibition on bone healing and remodeling by ZA. Nine adult female beagle dogs (2 to 3 yr old) were placed into 3 groups of 3 dogs each. Group I received 15 mL of sterile saline intravenously; group II received 2.5 mg of ZA intravenously; and group III received 5 mg of ZA intravenously. Forty-five days after treatment, all dogs underwent extraction of noncontiguous right and left mandibular first molars and second premolars. In group I, the right mandibular extraction sockets had nothing placed in them, whereas the left mandibular sockets had only ACS placed in them. In groups II and III, the right mandibular sockets had rhBMP-2/ACS placed in them, whereas the left mandibular sockets had only ACS placed. All extraction sockets were surgically closed. Tetracycline was given intravenously 5 and 12 days later, and all animals were euthanized 15 days after tooth extraction. The extraction sockets and rib and femur samples were harvested immediately after euthanasia, processed, and studied microscopically. A single dose of ZA significantly inhibited healing and bone remodeling in the area of the tooth extractions. The combination of rhBMP-2/ACS appeared to over-ride some of the bone remodeling inhibition of the ZA and increased bone fill in the extraction sites, and remodeling activity in the area was noted. The effects of rhBMP-2/ACS were confined to the area of the extraction sockets because bone activity at distant sites was not influenced. A single dose of ZA administered intravenously inhibits early healing of tooth extraction sockets and bone remodeling in this animal model. The

  4. Potential risk factors associated with contact dermatitis, lameness, negative emotional state, and fear of humans in broiler chicken flocks.

    Science.gov (United States)

    Bassler, A W; Arnould, C; Butterworth, A; Colin, L; De Jong, I C; Ferrante, V; Ferrari, P; Haslam, S; Wemelsfelder, F; Blokhuis, H J

    2013-11-01

    The objectives of this study were to 1) identify determinants of poor welfare in commercial broiler chicken flocks by studying the associations between selected resource-based measures (RBM, potential risk factors), such as litter quality and dark period, and animal-based welfare indicators (ABM), such as foot pad dermatitis and lameness, and 2) establish the breadth of effect of a risk factor by determining the range of animal welfare indicators associated with each of the risk factors (i.e., the number of ABM related to a specific RBM). Eighty-nine broiler flocks were inspected in 4 European countries (France, Italy, the United Kingdom, and the Netherlands) in a cross-sectional study. The ABM were contact dermatitis (measured using scores of foot-pad dermatitis and hock burn, respectively), lameness (measured as gait score), fear of humans (measured by the avoidance distance test and the touch test), and negative emotional state (measured using qualitative behavior assessment, QBA). In a first step, risk factors were identified by building a multiple linear regression model for each ABM. Litter quality was identified as a risk factor for contact dermatitis. Length of dark period at 3 wk old (DARK3) was a risk factor for the touch test result. DARK3 and flock age were risk factors for lameness, and the number of different stockmen and DARK3 were risk factors for QBA results. Next, the ABM were grouped according to risk factor and counted. Then, in a second step, associations between the ABM were investigated using common factor analysis. The breadth of a risk factor's effect was judged by combining the number (count) of ABM related to this factor and the strength of association between these ABM. Flock age and DARK3 appeared to affect several weakly correlated ABM, thus indicating a broad range of effects. Our findings suggest that manipulation of the predominant risk factors identified in this study (DARK3, litter quality, and slaughter age) could generate

  5. Effects of negative pressure wound therapy on the expression of EDA+ FN in granulation tissues of human diabetic foot wounds

    Directory of Open Access Journals (Sweden)

    Shao-ling YANG

    2017-04-01

    Full Text Available Objective  To investigate the effects of negative pressure wound therapy (NPWT on the expression of EDA+ FN in granulation tissues of human diabetic foot wounds. Methods  Forty patients with diabetic foot wounds fitting the inclusion criteria, admitted from Jan. 2014 to Jun. 2016, were randomly and equally apportioned to receive either NPWT or conventional gauze therapy (control for 14 days. Granulated tissue biopsies were collected before (0 day and after (14 day treatment in both groups. All biopsies were subdivided into two parts. One part was preserved in 4% paraformaldehyde for immunocytochemical staining of EDA+ FN, and the other part was stored at –80℃for Western blotting and PCR analysis of EDA+ FN. Results  The immunohistochemical analysis revealed that the mean area density of EDA+ FN increased in both NPWT group and control group at day 14 relative to day 0, but the change value of mean area density was higher in NPWT group than in control group (P<0.01. Western blotting showed that the relative protein levels of EDA+ FN increased in both NPWT group and control group at day 14 relative to day 0, but the change value of relative protein levels of EDA+ FN was higher in NPWT group than in control group (P<0.01. The real time PCR analysis demonstrated that the relative mRNA levels of EDA+ FN increased in both NPWT group and control group at day 14 relative to day 0, but the change value of relative mRNA levels of EDA+ FN was higher in NPWT group than in control group (P<0.01. The results demonstrated the higher protein and mRNA levels of EDA+ FN in NPWT group than that in control group. Conclusion  NPWT obviously enhances EDA+ FN expression in granulation tissue of diabetic foot wound, as a result promotes wound healing. DOI: 10.11855/j.issn.0577-7402.2017.03.09

  6. Effect of Several Negative Rounds of Human Papillomavirus and Cytology Co-testing on Safety Against Cervical Cancer: An Observational Cohort Study.

    Science.gov (United States)

    Castle, Philip E; Kinney, Walter K; Xue, Xiaonan; Cheung, Li C; Gage, Julia C; Zhao, Fang-Hui; Fetterman, Barbara; Poitras, Nancy E; Lorey, Thomas S; Wentzensen, Nicolas; Katki, Hormuzd A; Schiffman, Mark

    2018-01-02

    Current U.S. cervical cancer screening and management guidelines do not consider previous screening history, because data on multiple-round human papillomavirus (HPV) and cytology "co-testing" have been unavailable. To measure cervical cancer risk in routine practice after successive negative screening co-tests at 3-year intervals. Observational cohort study. Integrated health care system (Kaiser Permanente Northern California, Oakland, California). 990 013 women who had 1 or more co-tests from 2003 to 2014. 3- and 5-year cumulative detection of (risk for) cervical intraepithelial neoplasia grade 3, adenocarcinoma in situ, and cervical cancer (≥CIN3) in women with different numbers of negative co-tests, overall and within subgroups defined by previous co-test results or baseline age. Five-year ≥CIN3 risks decreased after each successive negative co-test screening round (0.098%, 0.052%, and 0.035%). Five-year ≥CIN3 risks for an HPV-negative co-test, regardless of the cytology result, nearly matched the performance (reassurance) of a negative co-test for each successive round of screening (0.114%, 0.061%, and 0.041%). By comparison, ≥CIN3 risks for the cytology-negative co-test, regardless of the HPV result, also decreased with each successive round, but 3-year risks were as high as 5-year risks after an HPV-negative co-test (0.199%, 0.065%, and 0.043%). No interval cervical cancer cases were diagnosed after the second negative co-test. Independently, ≥CIN3 risks decreased with age. Length of previous screening interval did not influence future ≥CIN3 risks. Interval-censored observational data. After 1 or more negative cervical co-tests (or HPV tests), longer screening intervals (every 5 years or more) might be feasible and safe. National Cancer Institute Intramural Research Program.

  7. When negation is not negation

    OpenAIRE

    Milicevic, Nataša

    2008-01-01

    In this paper I will discuss the formation of different types of yes/no questions in Serbian (examples in (1)), focusing on the syntactically and semantically puzzling example (1d), which involves the negative auxiliary inversion. Although there is a negative marker on the fronted auxiliary, the construction does not involve sentential negation. This coincides with the fact that the negative quantifying NPIs cannot be licensed. The question formation and sentential negation have similar synta...

  8. The Brain Basis of Positive and Negative Affect: Evidence from a Meta-Analysis of the Human Neuroimaging Literature.

    Science.gov (United States)

    Lindquist, Kristen A; Satpute, Ajay B; Wager, Tor D; Weber, Jochen; Barrett, Lisa Feldman

    2016-05-01

    The ability to experience pleasant or unpleasant feelings or to represent objects as "positive" or "negative" is known as representing hedonic "valence." Although scientists overwhelmingly agree that valence is a basic psychological phenomenon, debate continues about how to best conceptualize it scientifically. We used a meta-analysis of 397 functional magnetic resonance imaging (fMRI) and positron emission tomography studies (containing 914 experimental contrasts and 6827 participants) to test 3 competing hypotheses about the brain basis of valence: the bipolarity hypothesis that positive and negative affect are supported by a brain system that monotonically increases and/or decreases along the valence dimension, the bivalent hypothesis that positive and negative affect are supported by independent brain systems, and the affective workspace hypothesis that positive and negative affect are supported by a flexible set of valence-general regions. We found little evidence for the bipolar or bivalent hypotheses. Findings instead supported the hypothesis that, at the level of brain activity measurable by fMRI, valence is flexibly implemented across instances by a set of valence-general limbic and paralimbic brain regions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Novel Stromal Biomarkers in Human Breast Cancer Tissues Provide Evidence for the More Malignant Phenotype of Estrogen Receptor-Negative Tumors

    Directory of Open Access Journals (Sweden)

    Zahraa I. Khamis

    2011-01-01

    Full Text Available Research efforts were focused on genetic alterations in epithelial cancer cells. Epithelial-stromal interactions play a crucial role in cancer initiation, progression, invasion, angiogenesis, and metastasis; however, the active role of stroma in human breast tumorigenesis in relation to estrogen receptor (ER status of epithelial cells has not been explored. Using proteomics and biochemical approaches, we identified two stromal proteins in ER-positive and ER-negative human breast cancer tissues that may affect malignant transformation in breast cancer. Two putative biomarkers, T-cell receptor alpha (TCR-α and zinc finger and BRCA1-interacting protein with a KRAB domain (ZBRK1, were detected in leukocytes of ER-positive and endothelial cells of ER-negative tissues, respectively. Our data suggest an immunosuppressive role of leukocytes in invasive breast tumors, propose a multifunctional nature of ZBRK1 in estrogen receptor regulation and angiogenesis, and demonstrate the aggressiveness of ER-negative human breast carcinomas. This research project may identify new stromal drug targets for the treatment of breast cancer patients.

  10. 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....

  11. 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.

  12. Acute and chronic effects of NMDA receptor antagonists in rodents, relevance to negative symptoms of schizophrenia: a translational link to humans.

    Science.gov (United States)

    Neill, Joanna C; Harte, Michael K; Haddad, Peter M; Lydall, Emma S; Dwyer, Dominic M

    2014-05-01

    Negative symptoms of schizophrenia remain an unmet clinical need as they are common, persistent, respond poorly to existing treatments and lead to disability. Blunted affect, alogia, asociality, anhedonia and avolition are regarded as key negative symptoms despite DSM-IV-TR specifying a more limited range. The key to development of improved therapies is improved animal models that mimic the human condition in terms of behaviour and pathology and that predict efficacy of novel treatments in patients. Accumulating evidence shows that NMDA receptor (NMDAR) antagonists mimic cognitive deficits of relevance to schizophrenia in animals, along with associated pathological changes. This review examines evidence for the ability of NMDAR antagonists to mimic anhedonia and asociality, two negative symptoms of schizophrenia, in animals. The use of various species, paradigms and treatment regimens are reviewed. We conclude that sub-chronic treatment with NMDAR antagonists, typically PCP, induces social withdrawal in animals but not anhedonia. NMDAR antagonists have further effects in paradigms such as motivational salience that may be useful for mimicking other aspects of negative symptoms but these require further development. Sub-chronic treatment regimens of NMDAR antagonists also have some neurobiological effects of relevance to negative symptoms. It is our view that a sub-chronic treatment regime with NMDAR antagonists, particularly PCP, with animals tested following a wash-out period and in a battery of tests to assess certain behaviours of relevance to negative symptoms and social withdrawal (the animal equivalent of asociality) is valuable. This will enhance our understanding of the psycho and neuropathology of specific negative symptom domains and allow early detection of novel pharmacological targets. © 2013 Elsevier B.V. and ECNP All rights reserved.

  13. Prospective study of the impact of the Prosigna assay on adjuvant clinical decision-making in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative early-stage breast cancer.

    Science.gov (United States)

    Martín, Miguel; González-Rivera, Milagros; Morales, Serafín; de la Haba-Rodriguez, Juan; González-Cortijo, Lucía; Manso, Luis; Albanell, Joan; González-Martín, Antonio; González, Sónia; Arcusa, Angels; de la Cruz-Merino, Luis; Rojo, Federico; Vidal, María; Galván, Patricia; Aguirre, Elena; Morales, Cristina; Ferree, Sean; Pompilio, Kristen; Casas, Maribel; Caballero, Rosalía; Goicoechea, Uxue; Carrasco, Eva; Michalopoulos, Steven; Hornberger, John; Prat, Aleix

    2015-06-01

    Improved understanding of risk of recurrence (ROR) is needed to reduce cases of recurrence and more effectively treat breast cancer patients. The purpose of this study was to examine how a gene-expression profile (GEP), identified by Prosigna, influences physician adjuvant treatment selection for early breast cancer (EBC) and the effects of this influence on optimizing adjuvant treatment recommendations in clinical practice. A prospective, observational, multicenter study was carried out in 15 hospitals across Spain. Participating medical oncologists completed pre-assessment, post-assessment, and follow-up questionnaires recording their treatment recommendations and confidence in these recommendations, before and after knowing the patient's ROR. Patients completed questionnaires on decision-making, anxiety, and health status. Between June 2013 and January 2014, 217 patients enrolled and a final 200 were included in the study. Patients were postmenopausal, estrogen receptor positive, human epidermal growth hormone factor negative, and node negative with either stage 1 or stage 2 tumors. After receiving the GEP results, treatment recommendations were changed for 40 patients (20%). The confidence of medical oncologists in their treatment recommendations increased in 41.6% and decreased in 6.5% of total cases. Patients reported lower anxiety after physicians made treatment recommendations based on the GEP results (p anxiety about the selected adjuvant therapy decreased with use of the GEP.

  14. 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.

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

    International Nuclear Information System (INIS)

    Gao, Fei; Kishida, Tsunao; Ejima, Akika; Gojo, Satoshi; Mazda, Osam

    2013-01-01

    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

  16. 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

  17. Expression of Prostacyclin-Synthase in Human Breast Cancer: Negative Prognostic Factor and Protection against Cell Death In Vitro

    Directory of Open Access Journals (Sweden)

    Thomas Klein

    2015-01-01

    Full Text Available Endogenously formed prostacyclin (PGI2 and synthetic PGI2 analogues have recently been shown to regulate cell survival in various cell lines. To elucidate the significance of PGI2 in human breast cancer, we performed immunohistochemistry to analyze expression of prostacyclin-synthase (PGIS in 248 human breast cancer specimens obtained from surgical pathology files. We examined patients’ 10-year survival retrospectively by sending a questionnaire to their general practitioners and performed univariate analysis to determine whether PGIS expression correlated with patient survival. Lastly, the effects of PGI2 and its analogues on cell death were examined in a human breast cancer cell line (MCF-7 and a human T-cell leukemia cell line (CCRF-CEM. PGIS expression was observed in tumor cells in 48.7% of samples and was associated with a statistically significant reduction in 10-year survival (P=0.038; n=193. Transient transfection of PGIS into MCF-7 cells exposed to sulindac increased cell viability by 50% and exposure to carbaprostacyclin protected against sulindac sulfone induced apoptosis in CCRF-CEM cells. Expression of PGIS is correlated with a reduced patient survival and protects against cell death in vitro, suggesting that PGIS is a potential therapeutic target in breast cancer.

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

    Science.gov (United States)

    Gao, Fei; Kishida, Tsunao; Ejima, Akika; Gojo, Satoshi; Mazda, Osam

    2013-02-08

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. 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...

  20. Soluble granzymes are released during human endotoxemia and in patients with severe infection due to gram-negative bacteria

    NARCIS (Netherlands)

    Lauw, F. N.; Simpson, A. J.; Hack, C. E.; Prins, J. M.; Wolbink, A. M.; van Deventer, S. J.; Chaowagul, W.; White, N. J.; van der Poll, T.

    2000-01-01

    Extracellular release of granzymes is considered to reflect the involvement of cytotoxic T lymphocytes and NK cells in various disease states. To obtain insight into granzyme release during bacterial infection, granzyme levels were measured during experimental human endotoxemia and in patients with

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

    International Nuclear Information System (INIS)

    Xue, Jiangnan; Zhang, Xiaoshu; Zhao, Haiya; Fu, Qiang; Cao, Yanning; Wang, Yuesi; Feng, Xiaoying; Fu, Aili

    2011-01-01

    Research highlights: → LAIR-1 is expressed on human megakaryocytes from an early stage. → Up-regulation of LAIR-1 negatively regulates megakaryocytic differentiation of cell line. → 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 + CD41a + and CD41a + CD42b + cells. LAIR-1 is also detectable in a fraction of human cord blood CD34 + 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 + 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.

  2. Improvement of human cell line activation test (h-CLAT) using short-time exposure methods for prevention of false-negative results.

    Science.gov (United States)

    Narita, Kazuto; Ishii, Yuuki; Vo, Phuc Thi Hong; Nakagawa, Fumiko; Ogata, Shinichi; Yamashita, Kunihiko; Kojima, Hajime; Itagaki, Hiroshi

    2018-01-01

    Recently, animal testing has been affected by increasing ethical, social, and political concerns regarding animal welfare. Several in vitro safety tests for evaluating skin sensitization, such as the human cell line activation test (h-CLAT), have been proposed. However, similar to other tests, the h-CLAT has produced false-negative results, including in tests for acid anhydride and water-insoluble chemicals. In a previous study, we demonstrated that the cause of false-negative results from phthalic anhydride was hydrolysis by an aqueous vehicle, with IL-8 release from THP-1 cells, and that short-time exposure to liquid paraffin (LP) dispersion medium could reduce false-negative results from acid anhydrides. In the present study, we modified the h-CLAT by applying this exposure method. We found that the modified h-CLAT is a promising method for reducing false-negative results obtained from acid anhydrides and chemicals with octanol-water partition coefficients (LogK ow ) greater than 3.5. Based on the outcomes from the present study, a combination of the original and the modified h-CLAT is suggested for reducing false-negative results. Notably, the combination method provided a sensitivity of 95% (overall chemicals) or 93% (chemicals with LogK ow > 2.0), and an accuracy of 88% (overall chemicals) or 81% (chemicals with LogK ow > 2.0). We found that the combined method is a promising evaluation scheme for reducing false-negative results seen in existing in vitro skin-sensitization tests. In the future, we expect a combination of original and modified h-CLAT to be applied in a newly developed in vitro test for evaluating skin sensitization.

  3. Negative mass

    International Nuclear Information System (INIS)

    Hammond, Richard T

    2015-01-01

    Some physical aspects of negative mass are examined. Several unusual properties, such as the ability of negative mass to penetrate any armor, are analysed. Other surprising effects include the bizarre system of negative mass chasing positive mass, naked singularities and the violation of cosmic censorship, wormholes, and quantum mechanical results as well. In addition, a brief look into the implications for strings is given. (paper)

  4. Effects of spectral complexity and sound duration on automatic complex-sound pitch processing in humans - a mismatch negativity study.

    Science.gov (United States)

    Tervaniemi, M; Schröger, E; Saher, M; Näätänen, R

    2000-08-18

    The pitch of a spectrally rich sound is known to be more easily perceived than that of a sinusoidal tone. The present study compared the importance of spectral complexity and sound duration in facilitated pitch discrimination. The mismatch negativity (MMN), which reflects automatic neural discrimination, was recorded to a 2. 5% pitch change in pure tones with only one sinusoidal frequency component (500 Hz) and in spectrally rich tones with three (500-1500 Hz) and five (500-2500 Hz) harmonic partials. During the recordings, subjects concentrated on watching a silent movie. In separate blocks, stimuli were of 100 and 250 ms in duration. The MMN amplitude was enhanced with both spectrally rich sounds when compared with pure tones. The prolonged sound duration did not significantly enhance the MMN. This suggests that increased spectral rather than temporal information facilitates pitch processing of spectrally rich sounds.

  5. Transrepression of the estrogen receptor promoter by calcitriol in human breast cancer cells via two negative vitamin D response elements.

    Science.gov (United States)

    Swami, Srilatha; Krishnan, Aruna V; Peng, Lihong; Lundqvist, Johan; Feldman, David

    2013-08-01

    Calcitriol (1,25-dihydroxyvitamin D3), the hormonally active metabolite of vitamin D, exerts its anti-proliferative activity in breast cancer (BCa) cells by multiple mechanisms including the downregulation of the expression of estrogen receptor α (ER). We analyzed an ∼3.5 kb ER promoter sequence and demonstrated the presence of two potential negative vitamin D response elements (nVDREs), a newly identified putative nVDRE upstream at -2488 to -2473 bp (distal nVDRE) and a previously published sequence (proximal nVDRE) at -94 to -70 bp proximal to the P1 start site. Transactivation analysis using ER promoter deletion constructs and heterologous promoter-reporter constructs revealed that both nVDREs functioned to mediate calcitriol transrepression. In the electrophoretic mobility shift assay, the vitamin D receptor (VDR) showed strong binding to both nVDREs in the presence of calcitriol, and the chromatin immunoprecipitation assay demonstrated the recruitment of the VDR to the distal nVDRE site. Mutations in the 5' hexameric DNA sequence of the distal nVDRE resulted in the loss of calcitriol-mediated transrepression and the inhibition of protein-DNA complex formation, demonstrating the importance of these nucleotides in VDR DNA binding and transrepression. A putative nuclear factor-Y (NFY) binding site, identified within the distal nVDRE, led to the findings that NFY bound to the distal nVDRE site interfered with the binding of the VDR at the site and reduced calcitriol-mediated transrepression. In conclusion, the ER promoter region contains two negative VDREs that act in concert to bind to the VDR and both nVDREs are required for the maximal inhibition of ER expression by calcitriol. The suppression of ER expression and estrogen-mediated signaling by calcitriol in BCa cells suggests that vitamin D may be useful in the treatment of ER+ BCa.

  6. Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Miwa, Shinji; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Urata, Yasuo; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

    2016-01-01

    We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model. PMID:27689331

  7. Human apolipoprotein CIII gene expression is regulated by positive and negative cis-acting elements and tissue-specific protein factors

    International Nuclear Information System (INIS)

    Reue, K.; Leff, T.; Breslow, J.L.

    1988-01-01

    Apolipoprotein CIII (apoCIII) is a major protein constituent of triglyceride-rich lipoproteins and is synthesized primarily in the liver. Cis-acting DNA elements required for liver-specific apoCIII gene transcription were identified with transient expression assays in the human hepatoma (HepG2) and epithelial carcinoma (HeLa) cell lines. In liver cells, 821 nucleotides of the human apoCIII gene 5'-flanking sequence were required for maximum levels of gene expression, while the proximal 110 nucleotides alone were sufficient. No expression was observed in similar studies with HeLa cells. The level of expression was modulated by a combination of positive and negative cis-acting sequences, which interact with distinct sets of proteins from liver and HeLa cell nuclear extracts. The proximal positive regulatory region shares homology with similarly located sequences of other genes strongly expressed in the liver, including α 1 -antitrypsin and other apolipoprotein genes. The negative regulatory region is striking homologous to the human β-interferon gene regulatory element. The distal positive region shares homology with some viral enhancers and has properties of a tissue-specific enhancer. The regulation of the apoCIII gene is complex but shares features with other genes, suggesting shuffling of regulatory elements as a common mechanism for cell type-specific gene expression

  8. 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

  9. Negative liability

    NARCIS (Netherlands)

    Dari-Mattiacci, G.

    2009-01-01

    Negative and positive externalities pose symmetrical problems to social welfare. The law internalizes negative externalities by providing general tort liability rules. According to such rules, those who cause harm to others should pay compensation. In theory, in the presence of positive

  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. Increased Cytomegalovirus Secretion and Risks of Infant Infection by Breastfeeding Duration From Maternal Human Immunodeficiency Virus Positive Compared to Negative Mothers in Sub-Saharan Africa.

    Science.gov (United States)

    Musonda, Kunda G; Nyonda, Mary; Filteau, Suzanne; Kasonka, Lackson; Monze, Mwaka; Gompels, Ursula A

    2016-06-01

    Breastfeeding imparts beneficial immune protection and nutrition to infants for healthy growth, but it is also a route for human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) infection. In previous studies, we showed that HCMV adversely affects infant development in Africa, particularly with maternal HIV exposure. In this study, we analyzed infants risks for acquisition of HCMV infection from breastfeeding and compared HIV-positive and HIV-negative mothers. Two cohorts were studied in Zambia. (1) Two hundred sixty-one HIV-infected and HIV-uninfected mothers were compared for HCMV deoxyribonucleic acid (DNA) loads and genotypes (glycoprotein gO) in milk from birth to 4 months postpartum. (2) Maternally HIV-exposed and HIV-unexposed infants were compared for HCMV infection risk factors. The second cohort of 460 infants, from a trial of micronutrient-fortified complementary-food to breastfeeding, were studied between 6 and 18 months of age. Human cytomegalovirus seroprevalence was assayed, and logistic regression was used to calculate risk factors for HCMV infection, including maternal HIV exposure and breastfeeding duration. Human cytomegalovirus was detected in breast milk from 3 days to 4 months postpartum, with significantly raised levels in HIV-positive women and independent of genotype. In infants, HCMV antibody seroprevalence was 83% by 18 months age. Longer breastfeeding duration increased infection risk in maternally HIV-unexposed (odds ratio [OR] = 2.69 for 18 months vs 6 months vs never; 95% CI, 3.71-111.70; P breastfeeding, which is common in Africa, increased risk of HCMV infection in infants. Both HIV-positive and HIV-negative women had extended milk HCMV secretion. Women who were HIV-positive secreted higher HCMV levels, and for longer duration, with their children at increased infection risk. Human cytomegalovirus control is required to maintain health benefits of breastfeeding. © The Author 2016. Published by Oxford University Press

  12. The negative impact of Wnt signaling on megakaryocyte and primitive erythroid progenitors derived from human embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Prasuna Paluru

    2014-03-01

    Full Text Available The Wnt gene family consists of structurally related genes encoding secreted signaling molecules that have been implicated in many developmental processes, including regulation of cell fate and patterning during embryogenesis. Previously, we found that Wnt signaling is required for primitive or yolk sac-derived-erythropoiesis using the murine embryonic stem cell (ESC system. Here, we examine the effect of Wnt signaling on the formation of early hematopoietic progenitors derived from human ESCs. The first hematopoietic progenitor cells in the human ESC system express the pan-hematopoietic marker CD41 and the erythrocyte marker, glycophorin A or CD235. We have developed a novel serum-free, feeder-free, adherent differentiation system that can efficiently generate large numbers of CD41 + CD235+ cells. We demonstrate that this cell population contains progenitors not just for primitive erythroid and megakaryocyte cells but for the myeloid lineage as well and term this population the primitive common myeloid progenitor (CMP. Treatment of mesoderm-specified cells with Wnt3a led to a loss of hematopoietic colony-forming ability while the inhibition of canonical Wnt signaling with DKK1 led to an increase in the number of primitive CMPs. Canonical Wnt signaling also inhibits the expansion and/or survival of primitive erythrocytes and megakaryocytes, but not myeloid cells, derived from this progenitor population. These findings are in contrast to the role of Wnt signaling during mouse ESC differentiation and demonstrate the importance of the human ESC system in studying species-specific differences in development.

  13. Eighteen-Year Cryopreservation Does Not Negatively Affect the Pluripotency of Human Embryos: Evidence from Embryonic Stem Cell Derivation

    Science.gov (United States)

    Rungsiwiwut, Ruttachuk; Numchaisrika, Pranee; Ahnonkitpanit, Vichuda; Isarasena, Nipan; Virutamasen, Pramuan

    2012-01-01

    Abstract Human embryonic stem (hES) cells are considered to be a potential source for the therapy of human diseases, drug screening, and the study of developmental biology. In the present study, we successfully derived hES cell lines from blastocysts developed from frozen and fresh embryos. Seventeen- to eighteen-year-old frozen embryos were thawed, cultured to the blastocyst stage, and induced to form hES cells using human foreskin fibroblasts. The Chula2.hES cell line and the Chula4.hES and Chula5.hES cell lines were derived from blastocysts developed from frozen and fresh embryos, respectively. The cell lines expressed pluripotent markers, including alkaline phosphatase (AP), Oct3/4, stage-specific embryonic antigen (SSEA)-4, and tumor recognition antigen (TRA)-1-60 and TRA-1-81 as detected with immunocytochemistry. The real-time polymerase chain reaction (RT-PCR) results showed that the cell lines expressed pluripotent genes, including OCT3/4, SOX2, NANOG, UTF, LIN28, REX1, NODAL, and E-Cadherin. In addition, the telomerase activities of the cell lines were higher than in the fibroblast cells. Moreover, the cell lines differentiated into all three germ layers both in vitro and in vivo. The cell lines had distinct identities, as revealed with DNA fingerprinting, and maintained their normal karyotype after a long-term culture. This study is the first to report the successful derivation of hES cell lines in Thailand and that frozen embryos maintained their pluripotency similar to fresh embryos, as shown by the success of hES cell derivation, even after years of cryopreservation. Therefore, embryos from prolonged cryopreservation could be an alternative source for embryonic stem cell research. PMID:23514952

  14. 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......, and HPV-testing to detect cytologically diagnosed high grade lesions or cancer (HSIL+). Women from different areas in Tanzania were invited by public announcement to cervical cancer screening organized by Ocean Road Cancer Institute (Dar-es-Salaam). A total of 3,767 women were enrolled. Women underwent...

  15. CD63 tetraspanin is a negative driver of epithelial-to-mesenchymal transition in human melanoma cells.

    Science.gov (United States)

    Lupia, Antonella; Peppicelli, Silvia; Witort, Ewa; Bianchini, Francesca; Carloni, Vinicio; Pimpinelli, Nicola; Urso, Carmelo; Borgognoni, Lorenzo; Capaccioli, Sergio; Calorini, Lido; Lulli, Matteo

    2014-12-01

    The CD63 tetraspanin is highly expressed in the early stages of melanoma and decreases in advanced lesions, suggesting it as a possible suppressor of tumor progression. We employed loss- and gain-of-gene-function approaches to investigate the role of CD63 in melanoma progression and acquisition of the epithelial-to-mesenchymal transition (EMT) program. We used two human melanoma cell lines derived from primary tumors and one primary human melanoma cell line isolated from a cutaneous metastasis, differing by levels of CD63 expression. CD63-silenced melanoma cells showed enhanced motility and invasiveness with downregulation of E-cadherin and upregulation of N-cadherin and Snail. In parallel experiments, transient and stable ectopic expression of CD63 resulted in a robust reduction of cell motility, invasiveness, and protease activities, which was proportional to the increase in CD63 protein level. Transfected cells overexpressing the highest level of CD63 when transplanted into immunodeficient mice showed a reduced incidence and rate of tumor growth. Moreover, these cells showed a reduction of N-cadherin, Vimentin, Zeb1, and a-SMA, and a significant resistance to undergo an EMT program both in basal condition and in the following stimulation with TGFβ. Thus, our results establish a previously unreported mechanistic link between the tetraspanin CD63 and EMT abrogation in melanoma.

  16. Histamine H3 receptor density is negatively correlated with neural activity related to working memory in humans.

    Science.gov (United States)

    Ito, Takehito; Kimura, Yasuyuki; Seki, Chie; Ichise, Masanori; Yokokawa, Keita; Kawamura, Kazunori; Takahashi, Hidehiko; Higuchi, Makoto; Zhang, Ming-Rong; Suhara, Tetsuya; Yamada, Makiko

    2018-06-14

    The histamine H 3 receptor is regarded as a drug target for cognitive impairments in psychiatric disorders. H 3 receptors are expressed in neocortical areas, including the prefrontal cortex, the key region of cognitive functions such as working memory. However, the role of prefrontal H 3 receptors in working memory has not yet been clarified. Therefore, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) techniques, we aimed to investigate the association between the neural activity of working memory and the density of H 3 receptors in the prefrontal cortex. Ten healthy volunteers underwent both fMRI and PET scans. The N-back task was used to assess the neural activities related to working memory. H 3 receptor density was measured with the selective PET radioligand [ 11 C] TASP457. The neural activity of the right dorsolateral prefrontal cortex during the performance of the N-back task was negatively correlated with the density of H 3 receptors in this region. Higher neural activity of working memory was associated with lower H 3 receptor density in the right dorsolateral prefrontal cortex. This finding elucidates the role of H 3 receptors in working memory and indicates the potential of H 3 receptors as a therapeutic target for the cognitive impairments associated with neuropsychiatric disorders.

  17. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies

    Science.gov (United States)

    Lehmann, Brian D.; Bauer, Joshua A.; Chen, Xi; Sanders, Melinda E.; Chakravarthy, A. Bapsi; Shyr, Yu; Pietenpol, Jennifer A.

    2011-01-01

    Triple-negative breast cancer (TNBC) is a highly diverse group of cancers, and subtyping is necessary to better identify molecular-based therapies. In this study, we analyzed gene expression (GE) profiles from 21 breast cancer data sets and identified 587 TNBC cases. Cluster analysis identified 6 TNBC subtypes displaying unique GE and ontologies, including 2 basal-like (BL1 and BL2), an immunomodulatory (IM), a mesenchymal (M), a mesenchymal stem–like (MSL), and a luminal androgen receptor (LAR) subtype. Further, GE analysis allowed us to identify TNBC cell line models representative of these subtypes. Predicted “driver” signaling pathways were pharmacologically targeted in these cell line models as proof of concept that analysis of distinct GE signatures can inform therapy selection. BL1 and BL2 subtypes had higher expression of cell cycle and DNA damage response genes, and representative cell lines preferentially responded to cisplatin. M and MSL subtypes were enriched in GE for epithelial-mesenchymal transition, and growth factor pathways and cell models responded to NVP-BEZ235 (a PI3K/mTOR inhibitor) and dasatinib (an abl/src inhibitor). The LAR subtype includes patients with decreased relapse-free survival and was characterized by androgen receptor (AR) signaling. LAR cell lines were uniquely sensitive to bicalutamide (an AR antagonist). These data may be useful in biomarker selection, drug discovery, and clinical trial design that will enable alignment of TNBC patients to appropriate targeted therapies. PMID:21633166

  18. 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

  19. Pink-pigmented non-fermentative gram-negative rods associated with human infections: a clinical and diagnostic challenge.

    Science.gov (United States)

    Hogue, R; Graves, M; Moler, S; Janda, J M

    2007-06-01

    Over the past several decades, the appearance of pink-pigmented bacteria in clinical specimens has gone from being a microbiologic curiosity in the clinical laboratory to the recognition of these aerobic microorganisms as etiologic agents of human disease, most notably bloodstream infections. Advances in the fields of molecular taxonomy and phylogenetics indicate that at least four distinct genera and eight different species are associated with clinical infections in susceptible patient populations. However, these bacteria are slow growing and present multiple diagnostic challenges to the microbiology laboratory including culture, isolation, and identification to species rank. This article provides a current review of these unusual non-fermentative chromogenic bacteria including their disease spectrum, taxonomy, and laboratory identification. The review also highlights the pitfalls or shortcomings we currently have in our knowledge of these microbes and their disease-producing capabilities.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  2. A Risk Analysis Methodology to Address Human and Organizational Factors in Offshore Drilling Safety: With an Emphasis on Negative Pressure Test

    Science.gov (United States)

    Tabibzadeh, Maryam

    According to the final Presidential National Commission report on the BP Deepwater Horizon (DWH) blowout, there is need to "integrate more sophisticated risk assessment and risk management practices" in the oil industry. Reviewing the literature of the offshore drilling industry indicates that most of the developed risk analysis methodologies do not fully and more importantly, systematically address the contribution of Human and Organizational Factors (HOFs) in accident causation. This is while results of a comprehensive study, from 1988 to 2005, of more than 600 well-documented major failures in offshore structures show that approximately 80% of those failures were due to HOFs. In addition, lack of safety culture, as an issue related to HOFs, have been identified as a common contributing cause of many accidents in this industry. This dissertation introduces an integrated risk analysis methodology to systematically assess the critical role of human and organizational factors in offshore drilling safety. The proposed methodology in this research focuses on a specific procedure called Negative Pressure Test (NPT), as the primary method to ascertain well integrity during offshore drilling, and analyzes the contributing causes of misinterpreting such a critical test. In addition, the case study of the BP Deepwater Horizon accident and their conducted NPT is discussed. The risk analysis methodology in this dissertation consists of three different approaches and their integration constitutes the big picture of my whole methodology. The first approach is the comparative analysis of a "standard" NPT, which is proposed by the author, with the test conducted by the DWH crew. This analysis contributes to identifying the involved discrepancies between the two test procedures. The second approach is a conceptual risk assessment framework to analyze the causal factors of the identified mismatches in the previous step, as the main contributors of negative pressure test

  3. Vanillin attenuates negative effects of ultraviolet A on the stemness of human adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Lee, Sang Yeol; Park, See-Hyoung; Kim, Mi Ok; Lim, Inhwan; Kang, Mingyeong; Oh, Sae Woong; Jung, Kwangseon; Jo, Dong Gyu; Cho, Il-Hoon; Lee, Jongsung

    2016-10-01

    Ultraviolet A (UVA) irradiation induces various changes in cell biology. The objective of this study was to determine the effect of vanillin on UVA irradiation-induced damages in the stemness properties of human adipose tissue-derived mesenchymal stem cells (hAMSCs). UVA-antagonizing mechanisms of vanillin were also examined. The results revealed that vanillin attenuated UVA-induced reduction of the proliferative potential and stemness of hAMSCs evidenced by increased proliferative activity in BrdU incorporation assay and upregulation of stemness-related genes (OCT4, NANOG and SOX2) in response to vanillin treatment. UVA-induced reduction in mRNA level of hypoxia-inducible factor (HIF)-1α was significantly recovered by vanillin. In addition, the antagonizing effect of vanillin on UVA was found to be mediated by reduced production of PGE2 through inhibiting JNK and p38 MAPK. Taken together, these findings showed that vanillin could improve the reduced stemness of hAMSCs induced by UVA. The effect of vanillin is mediated by upregulating HIF-1α via inhibiting PGE2-cAMP signaling. Therefore, vanillin might be used as an antagonizing agent to mitigate the effects of UVA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Human Cytomegalovirus nuclear egress and secondary envelopment are negatively affected in the absence of cellular p53

    Energy Technology Data Exchange (ETDEWEB)

    Kuan, Man I; O’Dowd, John M.; Chughtai, Kamila; Hayman, Ian; Brown, Celeste J.; Fortunato, Elizabeth A., E-mail: lfort@uidaho.edu

    2016-10-15

    Human Cytomegalovirus (HCMV) infection is compromised in cells lacking p53, a transcription factor that mediates cellular stress responses. In this study we have investigated compromised functional virion production in cells with p53 knocked out (p53KOs). Infectious center assays found most p53KOs released functional virions. Analysis of electron micrographs revealed modestly decreased capsid production in infected p53KOs compared to wt. Substantially fewer p53KOs displayed HCMV-induced infoldings of the inner nuclear membrane (IINMs). In p53KOs, fewer capsids were found in IINMs and in the cytoplasm. The deficit in virus-induced membrane remodeling within the nucleus of p53KOs was mirrored in the cytoplasm, with a disproportionately smaller number of capsids re-enveloped. Reintroduction of p53 substantially recovered these deficits. Overall, the absence of p53 contributed to inhibition of the formation and function of IINMs and re-envelopment of the reduced number of capsids able to reach the cytoplasm. -- Highlights: •The majority of p53KO cells release fewer functional virions than wt cells. •Nucleocapsids do not efficiently exit the nucleus in p53KO cells. •Infoldings of the inner nuclear membrane are not efficiently formed in p53KO cells. •Cytoplasmic capsids are not efficiently re-enveloped in p53KO cells. •Reintroduction of p53 largely ameliorates these phenotypes.

  5. Human papillomavirus in anal biopsy tissues and liquid-based cytology samples of HIV-positive and HIV-negative Thai men who have sex with men

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    Tippawan Pankam

    2017-06-01

    Full Text Available Background: Men who have sex with men (MSM are at high risk of developing human papillomavirus (HPV-related anal cancer. We compared HPV genotypes in anal tissues (Bx and anal liquid-based cytology fluid (LBC from HIV-positive and HIV-negative MSM. Methods: Bx (32 normal, 41 low-grade squamous intraepithelial lesions (LSIL and 22 high-grade squamous intraepithelial lesions (HSIL, along with LBC from the same visit, were selected from 61 HIV-positive and 34 HIV-negative MSM who enrolled into a prospective cohort in Bangkok, Thailand. HPV genotyping was performed on Bx and LBC. Results: Any HPV and high-risk HPV (HR-HPV prevalence were 63.2% and 60.0% in Bx and 71.6% and 62.1% in LBC, respectively. HIV-positive MSM had higher rates of HR-HPV genotypes detection (70.5% vs. 47.1%, p=0.03 in LBC than HIV-negative MSM. HPV16 (27% was the most common HR-HPV found in HSIL tissue. In HIV-positive MSM, the frequency of HR-HPV detection increased with histopathologic grading in both Bx and LBC samples. HSIL was associated with the presence of any HR-HPV(OR 7.6 (95%CI 1.8–31.9; P=0.006 in LBC and in Bx((OR 5.6 (95%CI 1.4–22.7; P=0.02. Conclusions: Our data strongly support the integration of HR-HPV screening on LBC samples, along with HPV vaccination, into an anal cancer prevention program. Keywords: Human papillomavirus, Anal tissues, Men who have sex with men, HIV, Thailand

  6. Screening for human papillomavirus, cervical cytological abnormalities and associated risk factors in HIV-positive and HIV-negative women in Rwanda.

    Science.gov (United States)

    Mukanyangezi, M F; Sengpiel, V; Manzi, O; Tobin, G; Rulisa, S; Bienvenu, E; Giglio, D

    2018-02-01

    Cervical cancer is the major cause of death from cancer in Africa. We wanted to assess the prevalence of human papillomavirus (HPV) infections and associated risk factors and to determine whether HPV testing could serve as a screening method for squamous intraepithelial lesions (SILs) in Rwanda. We also wanted to obtain a broader understanding of the underlying risk factors for the establishment of HPV infection in Rwanda. A total of 206 HIV-positive women, 172 HIV-negative women and 22 women with unknown HIV status were recruited at the University Teaching Hospitals of Kigali (UTHK) and of Butare (UTHB) in Rwanda. Participants underwent an interview, cervical sampling for a Thinprep Pap test and a screening test analysing 37 HPV strains. Only 27% of HIV-positive women and 7% of HIV-negative women had been screened for cervical cancer before. HPV16 and HPV52 were the most common HPV strains. HIV-positive women were more commonly infected with high-risk (HR) HPV and multitype HPV than HIV-negative women. The sensitivity was 78% and the specificity 87% to detect high-grade SIL (HSIL) with HPV screening. Among HIV-negative women, being divorced was positively associated with HR-HPV infection, while hepatitis B, Trichomonas vaginalis infection and HR-HPV infection were factors positively associated with SILs. Ever having had gonorrhoea was positively associated with HR-HPV infection among HIV-positive women. HR-HPV infection and the number of live births were positively associated with SILs. The currently used quadrivalent vaccine may be insufficient to give satisfactory HPV coverage in Rwanda. HPV Screening may be effective to identify women at risk of developing cervical cancer, particularly if provided to high-risk patients. © 2017 British HIV Association.

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

    Science.gov (United States)

    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.

  8. Influence of exogenous lactoferrin on the oxidant/antioxidant balance and molecular profile of hormone receptor-positive and -negative human breast cancer cells in vitro.

    Science.gov (United States)

    Zalutskii, I V; Lukianova, N Y; Storchai, D M; Burlaka, A P; Shvets, Y V; Borikun, T V; Todor, I M; Lukashevich, V S; Rudnichenko, Y A; Chekhun, V F

    2017-07-01

    To investigate the mechanisms of cytotoxic activity and pro-/antioxidant effect of lactoferrin on hormone receptor-positive and receptor-negative breast cancer cells in vitro. The study was performed on receptor-positive (MCF-7, T47D) and receptor-negative (MDA-MB-231, MDA-MB-468) human breast cancer cell lines. Immunocytochemical staining, flow cytometry, low-temperature electron paramagnetic resonance, and the Comet assay were used. Upon treatment with lactoferrin, the increased levels of reactive oxygen species (ROS) (p < 0.05), NO generation rate by inducible NO-synthase (p < 0.05) and the level of "free" iron (p < 0.05) were observed. Moreover, the effects of lactoferrin were more pronounced in receptor-negative MDA-MB-231 and MDA-MB-468 cells. These changes resulted in increased expression of proapoptotic Bax protein (p < 0.05), reduced expression of the antiapoptotic Bcl-2 protein (p < 0.05) and level of not-oxidized mitochondrial cardiolipin (1.4-1.7-fold, p < 0.05). This, in turn, caused an increase in the percentage of apoptotic cells (by 14-24%, p < 0.05). Cytotoxic effects of lactoferrin were accompanied by an increase in the percentage of DNA in the comet tail and blocking cell cycle at G2/M phase, especially in receptor-negative cell lines. The study showed that exogenous lactoferrin causes a violation of an antioxidant balance by increasing the level of ROS, "free" iron and NO generation rate, resalting in the blocking of cell cycle at G2/M-phase and apoptosis of malignant cells.

  9. Prevalence of human Papilloma Virus in HIV-positive and HIV-negative patients in the State of Bahia: a pilot study

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    Conceição Queiroz

    Full Text Available Human Papilloma Virus (HPV plays a central role in the development of cervical cancer. However, other coexisting factors, such as HIV infection, must be present for this to occur. We evaluated the prevalence of HPV in HIV-positive and HIV-negative patients in the city of Salvador , Bahia, Brazil, and determined the most prevalent types of HPV in these patients. Fifty-five cases were selected from among patients attending three institutions providing cervical pathology services in the city of Salvador. HIV testing (Elisa/WB, HPV-DNA testing by PCR, colposcopy, cytology and biopsy were carried out in all patients. The histopathological results were classified as follows: 11 cases were normal/negative for neoplasia, 15 were diagnosed as cervical intraepithelial neoplasia grade 1 (CIN 1, 10 were CIN 2, 15 cases were CIN 3 and there were four cases of invasive squamous cell carcinoma. Among the 55 patients studied, 43 tested positive for HPV-DNA and 20 for HIV. All HIV-positive patients were positive for HPV-DNA. The most prevalent types of HPV were HPV 16, 52, 58, 53, 54, 33 and 51, and there was little difference between the groups of HIV-positive and HIV-negative patients with respect to the type of HPV encountered. The HIV-positive patients were found to be infected with a greater number of types of HPV than the HIV-negative patients. This study corroborates the existence of regional variations in the distribution of certain types of HPV, which is probably due to the particular ethnic constitution found in this region of Brazil.

  10. 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.

  11. Negative CO

    NARCIS (Netherlands)

    Meysman, F.J.R.; Montserrat, F.

    2017-01-01

    Negative emission technologies (NETs) target the removal of carbon dioxide (CO2) from the atmosphere, and are being actively investigated as a strategy to limit global warming to within the 1.5–2°C targets of the 2015 UN climate agreement. Enhanced silicate weathering (ESW) proposes to

  12. Negative Certainty

    Science.gov (United States)

    Ariso, José María

    2017-01-01

    The definitions of "negative knowledge" and the studies in this regard published to date have not considered the categorial distinction Wittgenstein established between knowledge and certainty. Hence, the important role that certainty, despite its omission, should have in these definitions and studies has not yet been shown. In this…

  13. Persistent Low-Risk and High-Risk Human Papillomavirus Infections of the Uterine Cervix in HIV-Negative and HIV-Positive Women

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    Sally N. Adebamowo

    2017-07-01

    Full Text Available BackgroundThe prevalence, persistence, and multiplicity of human papillomavirus (HPV infection appears different comparing HIV-positive to HIV-negative women. In this study, we examined prevalent, persistent, and multiple low- and high-risk cervical HPV infections in HIV-negative and HIV-positive women.MethodsWe studied 1,020 women involved in a study of HPV infection using SPF25/LiPA10. Two study visits were scheduled, at enrollment and 6 months afterward. At each study visit, research nurses used a cervical brush to collect samples of exfoliated cervical cells from the cervical os, from all the study participants. Exact logistic regression models were used to estimate associations between HIV and HPV infections.ResultsThe mean (SD age of the study participants was 38 (8 years, 56% were HIV-negative and 44% were HIV-positive. Among HIV-negative women at baseline, single low-risk HPV (lrHPV infections occurred in 12%; multiple lrHPV in 2%; single high-risk human papillomavirus (hrHPV infections in 9%, and multiple hrHPV infections in 2%. Single lrHPV infections were persistent in 6%, but there was no persistent multiple lrHPV infections. Single hrHPV infections were persistent in 4% while multiple hrHPV infections were persistent in 0.3%. Among HIV-positive women at baseline, single lrHPV infections occurred in 19%, multiple lrHPV in 6%, single hrHPV infections in 17%, and multiple hrHPV infections occurred in 12%. Single lrHPV infections were persistent in 9%, multiple lrHPV infections in 0.6%, single hrHPV infections in 13%, while multiple hrHPV were persistent in 3%. Prevalent, persistent, and multiple infections were more common in HIV-positive women, compared to HIV-negative women. In multivariate models adjusted for age, marital status, socioeconomic status, age at sexual initiation, and douching, the odds ratios comparing HIV-positive to HIV-negative women, were 2.09 (95% CI 1.47–2.97, p < 0.001 for prevalent lrHPV, 1.26 (95% CI

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

    International Nuclear Information System (INIS)

    Gradishar, William J

    2016-01-01

    Community-based oncologists are faced with challenges and opportunities when delivering quality patient care, including high patient volumes and diminished resources; however, there may be the potential to deliver increased patient education and subsequently improve outcomes. This review discusses the treatment of postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2- negative advanced breast cancer in order to illustrate considerations in the provision of pertinent quality education in the treatment of these patients and the management of therapy-related adverse events. An overview of endocrine-resistant breast cancer and subsequent treatment challenges is also provided. Approved treatment options for endocrine-resistant breast cancer include hormonal therapies and mammalian target of rapamycin inhibitors. Compounds under clinical investigation are also discussed

  15. 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

  16. Tamoxifen reduces P-gp-mediated multidrug resistance via inhibiting the PI3K/Akt signaling pathway in ER-negative human gastric cancer cells.

    Science.gov (United States)

    Mao, Zonglei; Zhou, Jin; Luan, Junwei; Sheng, Weihua; Shen, Xiaochun; Dong, Xiaoqiang

    2014-03-01

    Multidrug resistance (MDR), mediated by overexpression of drug efflux transporters such as P-glycoprotein (P-gp), is a major problem limiting successful chemotherapy of gastric cancer. Tamoxifen (TAM), a triphenylethylene nonsteroidal antiestrogen agent, shows broad-spectrum antitumor properties. Emerging studies demonstrated that TAM could significantly reduce the MDR in a variety of human cancers. Here we investigated the effects and possible underlying mechanisms of action of TAM on the reversion of MDR in ER-negative human gastric cancer cells. Our results demonstrated that in MDR phenotype SGC7901/CDDP gastric cancer cells TAM dramatically lowered the IC50 of CDDP, 5-FU and ADM, increased the intracellular Rhodamine123 accumulation and induced G0/G1 phase arrest, while G2/M phase decreased accordingly. Furthermore, at the molecular level, TAM substantially decreased the expression of P-gp, p-Akt and the Akt-regulated downstream effectors such as p-GSK-3β, p-BAD, Bcl-XL and cyclinD1 proteins without affecting the expression of t-Akt, t-GSK-3β, t-BAD proteins in SGC7901/CDDP cells. Thus, our findings demonstrate that TAM reverses P-gp-mediated gastric cancer cell MDR via inhibiting the PI3K/Akt signaling pathway. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells

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    Gutmann Anja

    2010-01-01

    Full Text Available Abstract Background ID proteins are dominant negative inhibitors of basic helix-loop-helix transcription factors that have multiple functions during development and cellular differentiation. Ectopic (over-expression of ID1 extends the lifespan of primary human epithelial cells. High expression levels of ID1 have been detected in multiple human malignancies, and in some have been correlated with unfavorable clinical prognosis. ID1 protein is localized at the centrosomes and forced (over-expression of ID1 results in errors during centrosome duplication. Results Here we analyzed the steady state expression levels of the four ID-proteins in 18 tumor cell lines and assessed the number of centrosome abnormalities. While expression of ID1, ID2, and ID3 was detected, we failed to detect protein expression of ID4. Expression of ID1 correlated with increased supernumerary centrosomes in most cell lines analyzed. Conclusions This is the first report that shows that not only ectopic expression in tissue culture but endogenous levels of ID1 modulate centrosome numbers. Thus, our findings support the hypothesis that ID1 interferes with centrosome homeostasis, most likely contributing to genomic instability and associated tumor aggressiveness.

  19. 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.

  20. A comparative study of human T-cell lymphotropic virus-associated myelopathy in HIV-positive and HIV-negative patients in KwaZulu-Natal

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    Hoosain F. Paruk

    2017-12-01

    Full Text Available Background: KwaZulu-Natal is an endemic area for HIV and human T-cell lymphotropic virus (HTLV infection. The main neurological manifestation of HTLV is HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP. The effect of HIV co-infection in patients with HAM/TSP is not well documented. Aims: To determine the prevalence of HIV seropositivity in patients with HAM/TSP and compare the clinical, laboratory and radiological features of patients mono-infected with HTLV and those dually infected with HTLV and HIV. Methods: Adult patients referred to the Neurology Department at Inkosi Albert Luthuli Central Hospital in KwaZulu-Natal, South Africa, for the period 01 January 2004 to 31 December 2015 with a positive HTLV serology were identified from the National Health Laboratory Service database. A retrospective chart review was conducted to identify all patients who had a diagnosis of HAM/TSP and to record their HIV status. Clinical, laboratory and radiological data were compared for HIV-positive and HIV-negative patients. Results: A total of 52 patients with HAM/TSP were identified. HIV results were available in 44 patients of whom 23 (52% patients were HIV co-infected. Patients who were HIV-positive had a younger age of presentation compared to HIV-negative patients (median: 31 vs 50 years, p = 0.002. HIV-positive patients had a median duration of symptoms at presentation of 12 months compared to 16 months for HIV-negative patients, but the difference did not reach statistical significance (p = 0.082. The CD4 cell counts of HIV-positive patients were well preserved with a median count of 781 cells/µL. Conclusions: HIV co-infection is commonly seen in the setting of HAM/TSP in KwaZulu-Natal. An interaction between the viruses may accelerate the development of HAM/TSP, leading to a younger age of presentation. Co-infection may have treatment implications because of CD4 counts being preserved in these patients.

  1. Lack of negative autocorrelations of daily food intake on successive days challenges the concept of the regulation of body weight in humans.

    Science.gov (United States)

    Levitsky, David A; Raea Limb, Ji Eun; Wilkinson, Lua; Sewall, Anna; Zhong, Yingyi; Olabi, Ammar; Hunter, Jean

    2017-09-01

    According to most theories, the amount of food consumed on one day should be negatively related to intake on subsequent days. Several studies have observed such a negative correlation between the amount consumed on one day and the amount consumed two to four days later. The present study attempted to replicate this observation by re-examining data from a previous study where all food ingested over a 30-day observation period was measured. Nine male and seven female participants received a vegan diet prepared, dispensed, and measured in a metabolic unit. Autocorrelations were performed on total food intake consume on one day and that consumed one to five days later. A significant positive correlation was detected between the weight of food eaten on one day and on the amount consumed on the following day (r = 0.29, 95% CI [0.37, 0.20]). No correlation was found between weights of food consumed on one day and up to twelve days later (r = 0.09, 95% CI [0.24, -0.06]), (r = 0.11, 95% CI [0.26, -0.0.26]) (r = 0.02, 95% CI [0.15, -0.7]) (r = -0.08, 95% CI [0.11, -0.09]). The same positive correlation with the previous day's intake was observed at the succeeding breakfast but not at either lunch or dinner. However, the participants underestimated their daily energy need resulting in a small, but statistically significant weight loss. Daily food intake increased slightly (13 g/day), but significantly, across the 30-day period. An analysis of the previous studies revealed that the negative correlations observed by others was caused by a statistical artifact resulting from normalizing data before testing for the correlations. These results, when combined with the published literature, indicate that there is little evidence that humans precisely compensate for the previous day's intake by altering the amount consumed on subsequent days. Moreover, the small but persistent increase in food intake suggests that physiological mechanisms that affect food intake

  2. Nasal carriage of methicillin-resistant coagulase-negative staphylococci in healthy humans is associated with occupational pig contact in a dose-response manner.

    Science.gov (United States)

    Li, Ling; Chen, Zhiyao; Guo, Dan; Li, Shunming; Huang, Jingya; Wang, Xiaolin; Yao, Zhenjiang; Chen, Sidong; Ye, Xiaohua

    2017-09-01

    This study aimed to explore the association between occupational pig contact and human methicillin-resistant coagulase-negative staphylococci (MRCoNS) carriage. We conducted a cross-sectional study of pig exposed participants and controls in Guangdong, China, using a multi-stage sampling design. Participants provided a nasal swab for MRCoNS analysis and resulting isolates were tested for antibiotic susceptibility. The dose-response relation was examined using log binomial regression or Poisson regression models. The adjusted prevalence of MRCoNS carriage in pig exposed participants was 1.67 times (95% CI: 1.32-2.11) higher than in controls. The adjusted average number of resistance to different antibiotic classes of MRCoNS isolates from pig exposed participants was 1.67 times (95% CI: 1.46-1.91) higher than those from controls. Notably, we found the frequency and duration of occupational pig contact was associated with increased prevalence and increased number of resistance to different antibiotic classes of MRCoNS in a dose-response manner. When examining these relations by MRCoNS species, there was still evidence of similar exposure-response relations. Additionally, the proportion of tetracycline-resistant and tet(M)-containing MRCoNS isolates was significantly higher in pig exposed participants than in controls. These findings suggested a potential transmission of MRCoNS from livestock to humans by occupational livestock contact, and the presence of phenotypic and genotypic tetracycline resistance may aid in the differentiation of animal origins of MRCoNS isolates. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. SENIEUR status of the originating cell donor negates certain 'anti-immunosenescence' effects of ebselen and N-acetyl cysteine in human T cell clone cultures.

    Science.gov (United States)

    Marthandan, Shiva; Freeburn, Robin; Steinbrecht, Susanne; Pawelec, Graham; Barnett, Yvonne

    2014-01-01

    Damage to T cells of the immune system by reactive oxygen species may result in altered cell function or cell death and thereby potentially impact upon the efficacy of a subsequent immune response. Here, we assess the impact of the antioxidants Ebselen and N-acetyl cysteine on a range of biological markers in human T cells derived from a SENIEUR status donor. In addition, the impact of these antioxidants on different MAP kinase pathways in T cells from donors of different ages was also examined. T cell clones were derived from healthy 26, 45 and SENIEUR status 80 year old people and the impact of titrated concentrations of Ebselen or N-acetyl cysteine on their proliferation and in vitro lifespan, GSH:GSSG ratio as well as levels of oxidative DNA damage and on MAP kinase signaling pathways was examined. In this investigation neither Ebselen nor N-acetyl cysteine supplementation had any impact on the biological endpoints examined in the T cells derived from the SENIEUR status 80 year old donor. This is in contrast to the anti-immunosenescent effects of these antioxidants on T cells from donors of 26 or 45 years of age. The analysis of MAP kinases showed that pro-apoptotic pathways become activated in T cells with increasing in vitro age and that Ebselen or N-acetyl cysteine could decrease activation (phosphorylation) in T cells from 26 or 45 year old donors, but not from the SENIEUR status 80 year old donor. The results of this investigation demonstrate that the biological phenotype of SENIEUR status derived human T cells negates the anti-immunosenescence effects of Ebselen and also N-acetyl cysteine. The results highlight the importance of pre-antioxidant intervention evaluation to determine risk-benefit.

  4. Identification of a negative allosteric site on human α4β2 and α3β4 neuronal nicotinic acetylcholine receptors.

    Directory of Open Access Journals (Sweden)

    Ryan E Pavlovicz

    Full Text Available Acetylcholine-based neurotransmission is regulated by cationic, ligand-gated ion channels called nicotinic acetylcholine receptors (nAChRs. These receptors have been linked to numerous neurological diseases and disorders such as Alzheimer's disease, Parkinson's disease, and nicotine addiction. Recently, a class of compounds has been discovered that antagonize nAChR function in an allosteric fashion. Models of human α4β2 and α3β4 nicotinic acetylcholine receptor (nAChR extracellular domains have been developed to computationally explore the binding of these compounds, including the dynamics and free energy changes associated with ligand binding. Through a blind docking study to multiple receptor conformations, the models were used to determine a putative binding mode for the negative allosteric modulators. This mode, in close proximity to the agonist binding site, is presented in addition to a hypothetical mode of antagonism that involves obstruction of C loop closure. Molecular dynamics simulations and MM-PBSA free energy of binding calculations were used as computational validation of the predicted binding mode, while functional assays on wild-type and mutated receptors provided experimental support. Based on the proposed binding mode, two residues on the β2 subunit were independently mutated to the corresponding residues found on the β4 subunit. The T58K mutation resulted in an eight-fold decrease in the potency of KAB-18, a compound that exhibits preferential antagonism for human α4β2 over α3β4 nAChRs, while the F118L mutation resulted in a loss of inhibitory activity for KAB-18 at concentrations up to 100 µM. These results demonstrate the selectivity of KAB-18 for human α4β2 nAChRs and validate the methods used for identifying the nAChR modulator binding site. Exploitation of this site may lead to the development of more potent and subtype-selective nAChR antagonists which may be used in the treatment of a number of neurological

  5. Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer.

    Science.gov (United States)

    Cheng, Qing; Chang, Jeffrey T; Geradts, Joseph; Neckers, Leonard M; Haystead, Timothy; Spector, Neil L; Lyerly, H Kim

    2012-04-17

    Although human epidermal growth factor receptor 2 (HER2) positive or estrogen receptor (ER) positive breast cancers are treated with clinically validated anti-HER2 or anti-estrogen therapies, intrinsic and acquired resistance to these therapies appears in a substantial proportion of breast cancer patients and new therapies are needed. Identification of additional molecular factors, especially those characterized by aggressive behavior and poor prognosis, could prioritize interventional opportunities to improve the diagnosis and treatment of breast cancer. We compiled a collection of 4,010 breast tumor gene expression data derived from 23 datasets that have been posted on the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. We performed a genome-scale survival analysis using Cox-regression survival analyses, and validated using Kaplan-Meier Estimates survival and Cox Proportional-Hazards Regression survival analyses. We conducted a genome-scale analysis of chromosome alteration using 481 breast cancer samples obtained from The Cancer Genome Atlas (TCGA), from which combined expression and copy number data were available. We assessed the correlation between somatic copy number alterations and gene expression using analysis of variance (ANOVA). Increased expression of each of the heat shock protein (HSP) 90 isoforms, as well as HSP transcriptional factor 1 (HSF1), was correlated with poor prognosis in different subtypes of breast cancer. High-level expression of HSP90AA1 and HSP90AB1, two cytoplasmic HSP90 isoforms, was driven by chromosome coding region amplifications and were independent factors that led to death from breast cancer among patients with triple-negative (TNBC) and HER2-/ER+ subtypes, respectively. Furthermore, amplification of HSF1 was correlated with higher HSP90AA1 and HSP90AB1 mRNA expression among the breast cancer cells without amplifications of these two genes. A collection of HSP90AA1, HSP90AB1 and HSF

  6. Comparison of the miRNA profiles in HPV-positive and HPV-negative tonsillar tumors and a model system of human keratinocyte clones

    International Nuclear Information System (INIS)

    Vojtechova, Zuzana; Sabol, Ivan; Salakova, Martina; Smahelova, Jana; Zavadil, Jiri; Turek, Lubomir; Grega, Marek; Klozar, Jan; Prochazka, Bohumir; Tachezy, Ruth

    2016-01-01

    Better insights into the molecular changes involved in virus-associated and -independent head and neck cancer may advance our knowledge of HNC carcinogenesis and identify critical disease biomarkers. Here we aimed to characterize the expression profiles in a matched set of well-characterized HPV-dependent and HPV-independent tonsillar tumors and equivalent immortalized keratinocyte clones to define potential and clinically relevant biomarkers of HNC of different etiology. Fresh frozen tonsillar cancer tissues were analyzed together with non-malignant tonsillar tissues and compared with cervical tumors and normal cervical tissues. Furthermore, relative miRNAs abundance levels of primary and immortalized human keratinocyte clones were evaluated. The global quantitation of miRNA gene abundance was performed using a TaqMan Low Density Array system. The confirmation of differentially expressed miRNAs was performed on a set of formalin-fixed paraffin-embedded tumor samples enriched for the tumor cell fraction by macrodissection. We defined 46 upregulated and 31 downregulated miRNAs characteristic for the HPV-positive tonsillar tumors and 42 upregulated miRNAs and 42 downregulated miRNAs characteristic for HPV-independent tumors. In comparison with the expression profiles in cervical tumors, we defined miR-141-3p, miR-15b-5p, miR-200a-3p, miR-302c-3p, and miR-9-5p as specific for HPV induced malignancies. MiR-335-5p, miR-579-3p, and miR-126-5p were shared by the expression profiles of HPV-positive tonsillar tumors and of the HPV immortalized keratinocyte clones, whereas miR-328-3p, miR-34c-3p, and miR-885-5p were shared by the miRNA profiles of HPV-negative tonsillar tumors and the HPV-negative keratinocytes. We identified the miRNAs characteristic for HPV-induced tumors and tonsillar tumors of different etiology, and the results were compared with those of the model system. Our report presents the basis for further investigations leading to the identification of

  7. Everolimus Plus Endocrine Therapy for Postmenopausal Women With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: A Clinical Trial.

    Science.gov (United States)

    Royce, Melanie; Bachelot, Thomas; Villanueva, Cristian; Özgüroglu, Mustafa; Azevedo, Sergio J; Cruz, Felipe Melo; Debled, Marc; Hegg, Roberto; Toyama, Tatsuya; Falkson, Carla; Jeong, Joon; Srimuninnimit, Vichien; Gradishar, William J; Arce, Christina; Ridolfi, Antonia; Lin, Chinjune; Cardoso, Fatima

    2018-03-22

    Cotargeting the mammalian target of rapamycin pathway and estrogen receptor may prevent or delay endocrine resistance in patients receiving first-line treatment for advanced breast cancer. To investigate the combination of everolimus plus endocrine therapy in first-line and second-line treatment settings for postmenopausal women with estrogen receptor-positive, human epidermal growth receptor 2-negative advanced breast cancer. In the multicenter, open-label, single-arm, phase 2 BOLERO-4 (Breast Cancer Trials of Oral Everolimus) clinical trial, 245 patients were screened for eligibility; 202 were enrolled between March 7, 2013, and December 17, 2014. A median follow-up of 29.5 months had been achieved by the data cutoff date (December 17, 2016). Patients received first-line treatment with everolimus, 10 mg/d, plus letrozole, 2.5 mg/d. Second-line treatment with everolimus, 10 mg/d, plus exemestane, 25 mg/d, was offered at the investigator's discretion upon initial disease progression. The primary end point was investigator-assessed progression-free survival in the first-line setting per Response Evaluation Criteria in Solid Tumors, version 1.0. Safety was assessed in patients who received at least 1 dose of study medication and at least 1 postbaseline safety assessment. A total of 202 women treated in the first-line setting had a median age of 64.0 years (interquartile range, 58.0-70.0 years) with metastatic (194 [96.0%]) or locally advanced (8 [4.0%]) breast cancer. Median progression-free survival was 22.0 months (95% CI, 18.1-25.1 months) with everolimus and letrozole. Median overall survival was not reached; 24-month estimated overall survival rate was 78.7% (95% CI, 72.1%-83.9%). Fifty patients started second-line treatment; median progression-free survival was 3.7 months (95% CI, 1.9-7.4 months). No new safety signals were observed. In the first-line setting, the most common all-grade adverse event was stomatitis (139 [68.8%]); the most common grade 3 to 4

  8. 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

  9. Gene expression profiling of Gram-negative bacteria-induced inflammation in human whole blood: The role of complement and CD14-mediated innate immune response

    Directory of Open Access Journals (Sweden)

    Corinna Lau

    2015-09-01

    Full Text Available Non-sterile pathogen-induced sepsis and sterile inflammation like in trauma or ischemia–reperfusion injury may both coincide with the life threatening systemic inflammatory response syndrome and multi-organ failure. Consequently, there is an urgent need for specific biomarkers in order to distinguish sepsis from sterile conditions. The overall aim of this study was to uncover putative sepsis biomarkers and biomarker pathways, as well as to test the efficacy of combined inhibition of innate immunity key players complement and Toll-like receptor co-receptor CD14 as a possible therapeutic regimen for sepsis. We performed whole blood gene expression analyses using microarray in order to profile Gram-negative bacteria-induced inflammatory responses in an ex vivo human whole blood model. The experiments were performed in the presence or absence of inhibitors of complement proteins (C3 and CD88 (C5a receptor 1 and CD14, alone or in combination. In addition, we used blood from a C5-deficient donor. Anti-coagulated whole blood was challenged with heat-inactivated Escherichia coli for 2 h, total RNA was isolated and microarray analyses were performed on the Affymetrix GeneChip Gene 1.0 ST Array platform. The initial experiments were performed in duplicates using blood from two healthy donors. C5-deficiency is very rare, and only one donor could be recruited. In order to increase statistical power, a technical replicate of the C5-deficient samples was run. Subsequently, log2-transformed intensities were processed by robust multichip analysis and filtered using a threshold of four. In total, 73 microarray chips were run and analyzed. The normalized and filtered raw data have been deposited in NCBI's Gene Expression Omnibus (GEO and are accessible with GEO Series accession number GSE55537. Linear models for microarray data were applied to estimate fold changes between data sets and the respective multiple testing adjusted p-values (FDR q-values. The

  10. 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.

  11. Patterns of resource utilization and cost for postmenopausal women with hormone-receptor–positive, human epidermal growth factor receptor-2–negative advanced breast cancer in Europe

    International Nuclear Information System (INIS)

    Jerusalem, Guy; Neven, Patrick; Marinsek, Nina; Zhang, Jie; Degun, Ravi; Benelli, Giancarlo; Saletan, Stephen; Ricci, Jean-François; Andre, Fabrice

    2015-01-01

    Healthcare resource utilization in breast cancer varies by disease characteristics and treatment choices. However, lack of clarity in guidelines can result in varied interpretation and heterogeneous treatment management and costs. In Europe, the extent of this variability is unclear. Therefore, evaluation of chemotherapy use and costs versus hormone therapy across Europe is needed. This retrospective chart review (N = 355) examined primarily direct costs for chemotherapy versus hormone therapy in postmenopausal women with hormone-receptor–positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer across 5 European countries (France, Germany, The Netherlands, Belgium, and Sweden). Total direct costs across the first 3 treatment lines were approximately €10 000 to €14 000 lower for an additional line of hormone therapy-based treatment versus switching to chemotherapy-based treatment. Direct cost difference between chemotherapy-based and hormone therapy-based regimens was approximately €1900 to €2500 per month. Chemotherapy-based regimens were associated with increased resource utilization (managing side effects; concomitant targeted therapy use; and increased frequencies of hospitalizations, provider visits, and monitoring tests). The proportion of patients taking sick leave doubled after switching from hormone therapy to chemotherapy. These results suggest chemotherapy is associated with increased direct costs and potentially with increased indirect costs (lower productivity of working patients) versus hormone therapy in HR+, HER2– advanced breast cancer. The online version of this article (doi:10.1186/s12885-015-1762-3) contains supplementary material, which is available to authorized users

  12. Gram-negative periodontal bacteria induce the activation of Toll-like receptors 2 and 4, and cytokine production in human periodontal ligament cells.

    Science.gov (United States)

    Sun, Ying; Shu, Rong; Li, Chao-Lun; Zhang, Ming-Zhu

    2010-10-01

    Periodontitis is a bacterially induced chronic inflammatory disease. Toll-like receptors (TLRs), which could recognize microbial pathogens, are important components in the innate and adaptive immune systems. Both qualitatively and quantitatively distinct immune responses might result from different bacteria stimulation and the triggering of different TLRs. This study explores the interaction of Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) with TLR2 and TLR4. We studied the gene expression changes of TLR2 and TLR4 and cytokine production (interleukin-1β, -6, -8, -10, and tumor necrosis factor-alpha) in human periodontal ligament cells (HPDLCs) stimulated with heat-killed bacteria or P. gingivalis lipopolysaccharide (LPS) in the presence or absence of monoclonal antibodies to TLR2 or TLR4 (anti-TLR2/4 mAb). Both test bacteria and 10 microg/ml P. gingivalis LPS treatment increased the gene expression of TLR2 and TLR4 and cytokine production in HPDLCs. In addition, these upregulations could be blocked by anti-TLR2/4 mAb. However, the expression of TLR4 mRNA in HPDLCs stimulated with 1 microg/ml P. gingivalis LPS was not increased. No differences were found in the cytokine production caused by 1 microg/ml P. gingivalis LPS treatment in the presence or absence of anti-TLR4 mAb. These patterns of gene expression and cytokine production indicate that Gram-negative periodontal bacteria or their LPS might play a role in triggering TLR2 and/or TLR4, and be of importance for the immune responses in periodontitis.

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

    Science.gov (United States)

    Raguideau, Sébastien; Plancade, Sandra; Pons, Nicolas; Leclerc, Marion; Laroche, Béatrice

    2016-12-01

    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 metabolic processes in

  14. 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

  15. Utility of the CPS+EG staging system in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer treated with neoadjuvant chemotherapy.

    Science.gov (United States)

    Marmé, Frederik; Lederer, Bianca; Blohmer, Jens-Uwe; Costa, Serban Dan; Denkert, Carsten; Eidtmann, Holger; Gerber, Bernd; Hanusch, Claus; Hilfrich, Jörn; Huober, Jens; Jackisch, Christian; Kümmel, Sherko; Loibl, Sibylle; Paepke, Stefan; Untch, Michael; von Minckwitz, Gunter; Schneeweiss, Andreas

    2016-01-01

    Pathologic complete response after neoadjuvant chemotherapy (NACT) correlates with overall survival (OS) in primary breast cancer. A recently described staging system based on pre-treatment clinical stage (CS), final pathological stage (PS), estrogen receptor (ER) status and nuclear grade (NG) leads to a refined estimation of prognosis in unselected patients. Its performance in luminal type breast cancers has not been determined. This study investigates the clinical utility of this CPS+EG score when restricted to hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) patients and compares the results to a cohort of unselected patients. The CPS+EG score was calculated for 6637 unselected patients and 2454 patients with HR+/HER2- tumours who received anthracycline/taxane-based NACT within 8 prospective German trials. Five-year disease-free survival (DFS) and OS were 75.6% and 84.1% for the unselected cohort and 80.6% and 87.8% for the HR+/HER2- subgroup, respectively. The CPS+EG system distinguished different prognostic groups with 5-year DFS ranging from 0% to 91%. The CPS+EG system leads to an improved categorisation of patients by outcome compared to CS, PS, ER or NG alone. When applying the CPS+EG score to the HR+/HER2- subgroup, a shift to lower scores was observed compared to the overall population, but 5-year DFS and OS for the individual scores were identical to that observed in the overall population. In HR+/HER2- patients, the CPS+EG staging system retains its ability to facilitate a refined stratification of patients according to outcome. It can help to select candidates for post-neoadjuvant clinical trials in luminal breast cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Gemcitabine Plus Docetaxel Versus Docetaxel in Patients With Predominantly Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer: A Randomized, Phase III Study by the Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Nielsen, Dorte L; Bjerre, Karsten D; Jakobsen, Erik H

    2011-01-01

    PURPOSE The objective of this phase III study was to compare the efficacy of gemcitabine plus docetaxel (GD) versus docetaxel in patients with advanced breast cancer. PATIENTS AND METHODS Predominantly human epidermal growth factor receptor 2 (HER2) -negative patients were randomly assigned...

  17. 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

  18. A novel one-class SVM based negative data sampling method for reconstructing proteome-wide HTLV-human protein interaction networks.

    Science.gov (United States)

    Mei, Suyu; Zhu, Hao

    2015-01-26

    Protein-protein interaction (PPI) prediction is generally treated as a problem of binary classification wherein negative data sampling is still an open problem to be addressed. The commonly used random sampling is prone to yield less representative negative data with considerable false negatives. Meanwhile rational constraints are seldom exerted on model selection to reduce the risk of false positive predictions for most of the existing computational methods. In this work, we propose a novel negative data sampling method based on one-class SVM (support vector machine, SVM) to predict proteome-wide protein interactions between HTLV retrovirus and Homo sapiens, wherein one-class SVM is used to choose reliable and representative negative data, and two-class SVM is used to yield proteome-wide outcomes as predictive feedback for rational model selection. Computational results suggest that one-class SVM is more suited to be used as negative data sampling method than two-class PPI predictor, and the predictive feedback constrained model selection helps to yield a rational predictive model that reduces the risk of false positive predictions. Some predictions have been validated by the recent literature. Lastly, gene ontology based clustering of the predicted PPI networks is conducted to provide valuable cues for the pathogenesis of HTLV retrovirus.

  19. 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...

  20. 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...

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

    OpenAIRE

    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 whe...

  2. Portrayal of negative qualities in a doctor as a potential teaching tool in medical ethics and humanism: Journey to the End of Night by Louis-Ferdinand Celine.

    Science.gov (United States)

    Wolf, G

    2006-02-01

    Fictional stories about physicians and patients are increasingly used as a powerful teaching resource for medical students. Very often, but not exclusively, stories of physicians as positive role models are selected to teach students virtues and ethical values. Negative role models are rarely used and if so, physicians are rather described as medical quacks in such fiction then exhibiting primarily a corrupted character. I suggest that a fictional story that presents exclusively a negative role model of a physician could also be a valuable, admittedly difficult, teaching resource to demonstrate the consequences of absolute loss of ethical standards and virtues in physicians. A not widely known example of this genre is Louis-Ferdinand Céline's (1894-1961) novel Voyage au bout de la nuit (Journey to the End of the Night), published in 1932. Having a strong autobiographical background, the novel described the adventures of the medicine student, Ferdinand Bardamu, during the first world war, in the African colonies as a trader, in the United States of America as factory worker, and later after finishing his education, as a doctor for the poor. Unfortunately, Dr Bardamu develops an unprofessional, even criminal behaviour, and may serve as a negative role model for the virtues of physicians. This article will familiarise the reader with the novel and its physician author.

  3. When mothering goes awry: Challenges and opportunities for utilizing evidence across rodent, nonhuman primate and human studies to better define the biological consequences of negative early caregiving.

    Science.gov (United States)

    Drury, Stacy S; Sánchez, Mar M; Gonzalez, Andrea

    2016-01-01

    This article is part of a Special Issue "Parental Care".Across mammalian species, mothers shape socio-emotional development and serve as essential external regulators of infant physiology, brain development, behavior patterns, and emotional regulation. Caregiving quality, consistency and predictability shape the infant's underlying neurobiological processes. Although the requirements for "optimal" caregiving differ across species, the negative long-term consequences of the absence of needed caregiving (e.g. neglect) or the presence of harmful/aversive caregiving (e.g. physical abuse), are translatable across species. Recognizing the significant potential of cross species comparisons in terms of defining underlying mechanisms, effective translation requires consideration of the evolutionary, ecological, and fundamental biological and developmental differences between and among species. This review provides both an overview of several success stories of cross-species translations in relation to negative caregiving and a template for future studies seeking to most effectively define the underlying biological processes and advance research dedicated to mitigating the lasting negative health consequences of child maltreatment. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Ikonomov, Ognian C.; Filios, Catherine; Sbrissa, Diego; Chen, Xuequn; Shisheva, Assia

    2013-01-01

    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 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 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 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 indirectly the

  5. [F-18-fluordeoxyglucose positron emission tomography on patients with differentiated thyroid cancer who present elevated human serum thyroglobulin levels and negative I-131 whole body scan].

    Science.gov (United States)

    Ruiz Franco-Baux, J V; Borrego Dorado, I; Gómez Camarero, P; Rodríguez Rodríguez, J R; Vázquez Albertino, R J; Navarro González, E; Astorga Jiménez, R

    2005-01-01

    This study aimed to evaluate the role of Fluorine-18-fluorodeoxyglucose positron emission tomography (PET-FDG) in patients with elevated serum thyroglobulin (hTg) levels where thyroid cancer tissue does not concentrate radioiodine, rendering false-negative results on I-131 scanning. Whole-body PET imaging using FDG was performed in 54 patients (37 female, 17 male) aged 17-88 years: 45 with papillary tumors and 9 with follicular tumors who were suspected of having recurrent thyroid carcinoma due to elevated thyroglobulin levels (hTg > 2 ng/ml) under thyroid-stimulating hormone (TSH > or = 30 microIU/ml) in whom the iodine scan was negative. All whole body scans were obtained with diagnostic doses (185 MBq). Whole body PET imaging was performed in fasting patients following i.v. administration of 370 MBq FDG while the patients were receiving full thyroid hormone replacement. Before PET, 99mTc methoxyisobutylisonitrile scintigraphy (99mTc-MIBI) was done in 14 patients and morphologic imaging in 26 by CT scan. Positive PET results confirmed the presence of hypermetabolic foci in 25/54 patients (46.29 %). Positive findings were found for PET-FDG in patients with hTg levels higher than 10 ng/ml receiving full thyroid hormone replacement. 99mTc-MIBI demonstrated lesions in 7/14 patients (50 %). PET-FDG and 99mTc-MIBI had congruent positive results in 4/7 patients. All the lesions found by CT were detected by PET-FDG, while recurrent disease was found in 12/21 patients with previous negative CT. These results suggest that PET-FDG seems to be a promising tool in the follow-up of thyroid cancer and should be considered in patients suffering from differentiated thyroid cancer with suspected recurrence and/or metastases by elevated thyroglobulin levels, and negative I-131 whole body scans. PET-FDG might be more useful at hTg levels > 10 ng/ml.

  6. 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...

  7. Genetic modification of human B-cell development: B-cell development is inhibited by the dominant negative helix loop helix factor Id3

    NARCIS (Netherlands)

    Jaleco, A. C.; Stegmann, A. P.; Heemskerk, M. H.; Couwenberg, F.; Bakker, A. Q.; Weijer, K.; Spits, H.

    1999-01-01

    Transgenic and gene targeted mice have contributed greatly to our understanding of the mechanisms underlying B-cell development. We describe here a model system that allows us to apply molecular genetic techniques to the analysis of human B-cell development. We constructed a retroviral vector with a

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

    OpenAIRE

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

    2015-01-01

    Objective 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. Methods A total of 439 patients with ASCUS or LSIL were included. The association between age groups and the diagnostic performances of ...

  9. 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

    " observed among older women. Recent sexual partners were a strong determinant of HPV appearance irrespective of age. Lifetime number of sexual partners was a significant risk factor for HPV appearance among older women, even after adjustment for recent sexual behavior. In addition, menopause was associated...... in older women using multiple logistic regression. For comparison, a younger cohort of women examined under identical study settings was included. This prospective cohort study comprised 1,577 older women (age 40-50 at enrolment) and 2,920 women aged 22-32. Participants were interviewed and underwent...... with a non-significantly increased risk of HPV appearance at follow-up. In conclusion, appearance of HPV in previously HPV-negative older women may be due to both recent sexual behavior and previous exposure that is, reactivation of a latent HPV infection....

  10. Storage of the complement components C4, C3, and C 3-activator in the human liver as PAS-negative globular hyaline bodies.

    Science.gov (United States)

    Storch, W; Riedel, H; Trautmann, B; Justus, J; Hiemann, D

    1982-01-01

    Liver biopsies of a 58-year-old clinically healthy patient with a hepatomegaly and intracisternal PAS-negative globular hyaline bodies were immunofluorescent-optically examined for the content of the complement components C 1 q, C 4, C 9, C 1-inactivator, C 3-activator. Further examinations were performed for fibrinogen, IgG, IgA, IgM, IgD, IgE, L-chain (type chi and lambda), alpha 1-antitrypsin, alpha 1-fetoprotein, alpha 1- and alpha 2-glycoprotein, cholinesterase, ceruloplasmin, myoglobin, hemopexin, HBsAg and HBsAg. Th inclusion bodies reacted with antisera against the complement components C 4, C 3 and C 3-activator, as also identified by double immunofluorescence. Probably this is a disturbance of the protein metabolism of the liver cell with abnormal complement storage in the presence of normal total complement and normal complement components in the serum.

  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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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 Cu 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

    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.

  13. 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.

  14. 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.

  15. Nuclear detection of Y-box protein-1 (YB-1) closely associates with progesterone receptor negativity and is a strong adverse survival factor in human breast cancer

    International Nuclear Information System (INIS)

    Dahl, Edgar; Dunn, Sandra E; Mertens, Peter R; En-Nia, Abdelaziz; Wiesmann, Frank; Krings, Renate; Djudjaj, Sonja; Breuer, Elisabeth; Fuchs, Thomas; Wild, Peter J; Hartmann, Arndt

    2009-01-01

    Y-box binding protein-1 (YB-1) is the prototypic member of the cold shock protein family that fulfills numerous cellular functions. In the nucleus YB-1 protein orchestrates transcription of proliferation-related genes, whereas in the cytoplasm it associates with mRNA and directs translation. In human tumor entities, such as breast, lung and prostate cancer, cellular YB-1 expression indicates poor clinical outcome, suggesting that YB-1 is an attractive marker to predict patients' prognosis and, potentially, is suitable to individualize treatment protocols. Given these predictive qualities of YB-1 detection we sought to establish a highly specific monoclonal antibody (Mab) for diagnostic testing and its characterization towards outcome prediction (relapse-free and overall survival). Hybridoma cell generation was carried out with recombinant YB-1 protein as immunogen and Mab characterization was performed using immunoblotting and ELISA with recombinant and tagged YB-1 proteins, as well as immunohistochemistry of healthy and breast cancer specimens. Breast tumor tissue array staining results were analyzed for correlations with receptor expression and outcome parameters. YB-1-specific Mab F-E2G5 associates with conformational binding epitopes mapping to two domains within the N-terminal half of the protein and detects nuclear YB-1 protein by immunohistochemistry in paraffin-embedded breast cancer tissues. Prognostic evaluation of Mab F-E2G5 was performed by immunohistochemistry of a human breast cancer tissue microarray comprising 179 invasive breast cancers, 8 ductal carcinoma in situ and 37 normal breast tissue samples. Nuclear YB-1 detection in human breast cancer cells was associated with poor overall survival (p = 0.0046). We observed a close correlation between nuclear YB-1 detection and absence of progesterone receptor expression (p = 0.002), indicating that nuclear YB-1 detection marks a specific subgroup of breast cancer. Likely due to limitation of sample

  16. Fluid Redistribution and Heart Rate in Humans During Whole-Body Tilting, G(z) Centrifugation, and Lower Body Negative Pressure

    Science.gov (United States)

    Watenpaugh, D. E.; Breit, G. A.; Ballard, R. E.; Murthy, G.; Hargens, A. R.

    1994-01-01

    Gravity creates blood pressure gradients which redistribute body fluids towards the feet. Positive G(z) centrifugation and lower body negative pressure (LBNP) have been proposed to simulate these and other effects of gravity during long-term existence in microgravity. We hypothesized that the magnitude of upper-to-lower body fluid redistribution would increase according to the following order: short-arm centrifugation (SAC), long-arm centrifugation (LAC), head-up tilt (HUT), and LBNP. To test this hypothesis, we employed strain gauge plethysmography of the neck, thigh and calf during HUT and supine SAC and LAC up to lG(z) at the feet, and during supine LBNP to 100 mm Hg. Supine 100 mm Hg LBNP generates footward force and produces transmural blood pressures in the foot approximately equal to 1 G(z) (90 deg) HUT. Heart rate was measured via cardiotachometry. Control measurements were made while supine. SAC and LAC elicited similar increases in thigh volume at 1 G(z) (2.3 +/- 0.4 and 2.1 +/- 0.1%, respectively; mean +/- se, n greater than or equal to 7). At 100 mm Hg LBNP, thigh volume increased (3.4 +/- 0.3%) significantly more than during l G(z) centrifugation (p less than 0.05). Surprisingly, due to a paradoxical 0.6% reduction of thigh volume between 0.8 and 1.0 G(z) HUT, thigh volume was increased only 0.6 +/- 0.3% at 1 G(z) HUT. The calf demonstrated similar, although less definitive, responses to the various gravitational stimuli. Neck volume tended to decrease less during HUT than during the other stimuli. Heart rate increased similarly during HUT (18 +/- 2 beats/min) and LAC (12 +/- 2 beats/min), and exhibited still greater elevation during LBNP (29 +/- 4 beats/min), yet did not increase during SAC. These results suggest upright posture activates mechanisms that counteract footward fluid redistribution which are not activated during supine applications of simulated gravity. LAC more closely approximated effects of normal gravity (HUT) than LBNP. Therefore

  17. Comparison of Different Sample Preparation Protocols Reveals Lysis Buffer-Specific Extraction Biases in Gram-Negative Bacteria and Human Cells.

    Science.gov (United States)

    Glatter, Timo; Ahrné, Erik; Schmidt, Alexander

    2015-11-06

    We evaluated different in-solution and FASP-based sample preparation strategies for absolute protein quantification. Label-free quantification (LFQ) was employed to compare different sample preparation strategies in the bacterium Pseudomonas aeruginosa and human embryonic kidney cells (HEK), and organismal-specific differences in general performance and enrichment of specific protein classes were noted. The original FASP protocol globally enriched for most proteins in the bacterial sample, whereas the sodium deoxycholate in-solution strategy was more efficient with HEK cells. Although detergents were found to be highly suited for global proteome analysis, higher intensities were obtained for high-abundant nucleic acid-associated protein complexes, like the ribosome and histone proteins, using guanidine hydrochloride. Importantly, we show for the first time that the observable total proteome mass of a sample strongly depends on the sample preparation protocol, with some protocols resulting in a significant underestimation of protein mass due to incomplete protein extraction of biased protein groups. Furthermore, we demonstrate that some of the observed abundance biases can be overcome by incorporating a nuclease treatment step or, alternatively, a correction factor for complementary sample preparation approaches.

  18. 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.

  19. Complex sound processing during human REM sleep by recovering information from long-term memory as revealed by the mismatch negativity (MMN).

    Science.gov (United States)

    Atienza, M; Cantero, J L

    2001-05-18

    Perceptual learning is thought to be the result of neural changes that take place over a period of several hours or days, allowing information to be transferred to long-term memory. Evidence suggests that contents of long-term memory may improve attentive and pre-attentive sensory processing. Therefore, it is plausible to hypothesize that learning-induced neural changes that develop during wakefulness could improve automatic information processing during human REM sleep. The MMN, an objective measure of the automatic change detection in auditory cortex, was used to evaluate long-term learning effects on pre-attentive processing during wakefulness and REM sleep. When subjects learned to discriminate two complex auditory patterns in wakefulness, an increase in the MMN was obtained in both wake and REM states. The automatic detection of the infrequent complex auditory pattern may therefore be improved in both brain states by reactivating information from long-term memory. These findings suggest that long-term learning-related neural changes are accessible during REM sleep as well.

  20. Glycogen synthase kinase-3beta (GSK3beta) negatively regulates PTTG1/human securin protein stability, and GSK3beta inactivation correlates with securin accumulation in breast tumors.

    Science.gov (United States)

    Mora-Santos, Mar; Limón-Mortés, M Cristina; Giráldez, Servando; Herrero-Ruiz, Joaquín; Sáez, Carmen; Japón, Miguel Á; Tortolero, Maria; Romero, Francisco

    2011-08-26

    PTTG1, also known as securin, is an inactivating partner of separase, the major effector for chromosome segregation during mitosis. At the metaphase-to-anaphase transition, securin is targeted for proteasomal destruction by the anaphase-promoting complex or cyclosome, allowing activation of separase. In addition, securin is overexpressed in metastatic or genomically instable tumors, suggesting a relevant role for securin in tumor progression. Stability of securin is regulated by phosphorylation; some phosphorylated forms are degraded out of mitosis, by the action of the SKP1-CUL1-F-box protein (SCF) complex. The kinases targeting securin for proteolysis have not been identified, and mechanistic insight into the cause of securin accumulation in human cancers is lacking. Here, we demonstrate that glycogen synthase kinase-3β (GSK3β) phosphorylates securin to promote its proteolysis via SCF(βTrCP) E3 ubiquitin ligase. Importantly, a strong correlation between securin accumulation and GSK3β inactivation was observed in breast cancer tissues, indicating that GSK3β inactivation may account for securin accumulation in breast cancers.

  1. Vorinostat enhances protein stability of p27 and p21 through negative regulation of Skp2 and Cks1 in human breast cancer cells.

    Science.gov (United States)

    Uehara, Norihisa; Yoshizawa, Katsuhiko; Tsubura, Airo

    2012-07-01

    Vorinostat is a histone deacetylase inhibitor that blocks cancer cell proliferation through the regulation of cyclin-dependent kinase inhibitors. We, herein, examined the involvement of S-phase kinase-associated protein 2 (Skp2) and cyclin-dependent kinase subunit 1 (Cks1), the components of the SCFSkp2-Cks1 (Skp1/Cul1/F-box protein) ubiquitin ligase complex, in the regulation of p27 and p21 during vorinostat-induced growth arrest of MDA-MB-231 and MCF-7 human breast cancer cells. Vorinostat significantly reduced BrdU incorporation in MDA-MB-231 and MCF-7 cells, which was associated with increased p27 and p21 protein levels without concomitant induction of p27 mRNA. Vorinostat-induced accumulation of p27 and p21 proteins was inversely correlated with the mRNA and protein levels of Skp2 and Cks1. Cycloheximide chase analysis revealed that vorinostat increased the half-life of p27 and p21 proteins. The accumulation of p27 and p21 proteins was attenuated by forced expression of Skp2 and Cks1, which conferred resistance to the vorinostat-induced S-phase reduction. These results suggest that vorinostat-induced growth arrest may be in part due to the enhanced protein stability of p27 and p21 through the downregulation of Skp2 and Cks1.

  2. SM-1 negative ion source

    International Nuclear Information System (INIS)

    Huang Zhenjun; Wang Jianzhen

    1987-01-01

    The working principle and characteristics of SM-1 Negative Ion Source is mainly introduced. In the instrument, there is a device to remove O 3 . This instrument can keep high density of negative ions which is generated by the electrical coronas setting out electricity at negative high voltage and can remove the O 3 component which is harmful to the human body. The density of negative ions is higher than 2.5 x 10 6 p./cm 3 while that of O 3 components is less than 1 ppb at the distance of 50 cm from the panel of the instrument. The instrument sprays negative ions automatically without the help of electric fan, so it works noiselessly. It is widely used in national defence, industry, agriculture, forestry, stock raising, sidelines and in the places with an equipment of low density of negative ion or high concentration of O 3 components. Besides, the instrument may also be used to treat diseases, to prevent against rot, to arrest bacteria, to purify air and so on

  3. Dominant-negative effect of hetero-oligomerization on the function of the human immunodeficiency virus type 1 envelope glycoprotein complex

    International Nuclear Information System (INIS)

    Herrera, Carolina; Klasse, Per Johan; Kibler, Christopher W.; Michael, Elizabeth; Moore, John P.; Beddows, Simon

    2006-01-01

    The human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein forms trimers that mediate interactions with the CD4 receptor and a co-receptor on the target cell surface, thereby triggering viral fusion with the cell membrane. Cleavage of Env into its surface, gp120, and transmembrane, gp41, moieties is necessary for activation of its fusogenicity. Here, we produced pseudoviruses with phenotypically mixed wild-type (Wt) and mutant, cleavage-incompetent Env in order to quantify the effects of incorporating uncleaved Env on virion infectivity, antigenicity and neutralization sensitivity. We modeled the relative infectivity of three such phenotypically mixed viral strains, JR-FL, HXBc2 and a derivative of the latter, 3.2P, as a function of the relative amount of Wt Env. The data were fit very closely (R 2 > 0.99) by models which assumed that only Wt homotrimers were functional, with different approximate thresholds of critical numbers of functional trimers per virion for the three strains. We also produced 3.2P pseudoviruses containing both a cleavage-competent Env that is defective for binding the neutralizing monoclonal antibody (NAb) 2G12, and a cleavage-incompetent Env that binds 2G12. The 2G12 NAb was not able to reduce the infectivity of these pseudoviruses detectably. Their neutralization by the CD4-binding site-directed agents CD4-IgG2 and NAb b12 was also unaffected by 2G12 binding to uncleaved Env. These results further strengthen the conclusion that only homotrimers consisting of cleaved Env are functional. They also imply that the function of a trimer is unaffected sterically by the binding of an antibody to an adjacent trimer

  4. Negative-ion states

    International Nuclear Information System (INIS)

    Compton, R.N.

    1982-01-01

    In this brief review, we discuss some of the properties of atomic and molecular negative ions and their excited states. Experiments involving photon reactions with negative ions and polar dissociation are summarized. 116 references, 14 figures

  5. Negative ion detachment processes

    International Nuclear Information System (INIS)

    Champion, R.L.; Doverspike, L.D.

    1990-10-01

    This paper discusses the following topics: H - and D - collisions with atomic hydrogen; collisional decomposition of SF 6 - ; two-electron loss processes in negative ion collisions; associative electron detachment; and negative ion desorption from surfaces

  6. NRF2 Signaling Negatively Regulates Phorbol-12-Myristate-13-Acetate (PMA-Induced Differentiation of Human Monocytic U937 Cells into Pro-Inflammatory Macrophages.

    Directory of Open Access Journals (Sweden)

    Min-Gu Song

    Full Text Available Blood monocytes are recruited to injured tissue sites and differentiate into macrophages, which protect against pathogens and repair damaged tissues. Reactive oxygen species (ROS are known to be an important contributor to monocytes' differentiation and macrophages' function. NF-E2-related factor 2 (NRF2, a transcription factor regulating cellular redox homeostasis, is known to be a critical modulator of inflammatory responses. We herein investigated the role of NRF2 in macrophage differentiation using the human monocytic U937 cell line and phorbol-12-myristate-13-acetate (PMA. In U937 cells with NRF2 silencing, PMA-stimulated cell adherence was significantly facilitated when compared to control U937 cells. Both transcript and protein levels for pro-inflammatory cytokines, including interleukine-1β (IL-1β, IL-6, and tumor necrosis factor-α (TNFα were highly elevated in PMA-stimulated NRF2-silenced U937 compared to the control. In addition, PMA-inducible secretion of monocyte chemotactic protein 1 (MCP-1 was significantly high in NRF2-silenced U937. As an underlying mechanism, we showed that NRF2-knockdown U937 retained high levels of cellular ROS and endoplasmic reticulum (ER stress markers expression; and subsequently, PMA-stimulated levels of Ca2+ and PKCα were greater in NRF2-knockdown U937 cells, which caused enhanced nuclear accumulation of nuclear factor-ҡB (NFҡB p50 and extracellular signal-regulated kinase (ERK-1/2 phosphorylation. Whereas the treatment of NRF2-silenced U937 cells with pharmacological inhibitors of NFҡB or ERK1/2 largely blocked PMA-induced IL-1β and IL-6 expression, indicating that these pathways are associated with cell differentiation. Taken together, our results suggest that the NRF2 system functions to suppress PMA-stimulated U937 cell differentiation into pro-inflammatory macrophages and provide evidence that the ROS-PKCα-ERK-NFҡB axis is involved in PMA-facilitated differentiation of NRF2-silenced U937

  7. High-throughput and simultaneous analysis of eight central-acting muscle relaxants in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry in the positive and negative ionization modes.

    Science.gov (United States)

    Ogawa, Tadashi; Hattori, Hideki; Kaneko, Rina; Ito, Kenjiro; Iwai, Masae; Mizutani, Yoko; Arinobu, Tetsuya; Ishii, Akira; Seno, Hiroshi

    2011-06-01

    In this report, a high-throughput and sensitive method for analysis of eight central-acting muscle relaxants in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in the positive and negative ionization modes using tolbutamide as internal standard is presented. After pretreatment of a plasma sample by solid-phase extraction with an Oasis HLB cartridge, muscle relaxants were analyzed by UPLC with Acquity UPLC BEH C(18) column and Acquity TQD tandem quadrupole mass spectrometer equipped with an electrospray ionization interface. The calibration curves for muscle relaxants spiked into human plasma equally showed good linearities in the nanogram per milliliter order range. The detection limits (signal-to-noise ratio = 3) was as low as 0.1-2 ng/mL. The method gave satisfactory recovery rates, accuracy, and precision for quality control samples spiked with muscle relaxants. To further validate the present method, 250 mg of chlorphenesin carbamate was orally administered to a healthy male volunteer, and the concentrations of chlorphenesin carbamate in plasma were measured 0.5, 1, 2, 4, 6, and 8 h after dosing; their concentrations in human plasma were between 0.62 and 2.44 μg/mL. To our knowledge, this is the first report describing simultaneous analysis of over more than two central-acting muscle relaxants by liquid chromatography-tandem mass spectrometry. This has been realized by the capability of our instrument for simultaneous multiple reaction monitoring of the target compounds in both positive and negative ionization modes. Therefore, the present method seems very useful in forensic and clinical toxicology and pharmacokinetic studies.

  8. Sentential Negation in English

    Science.gov (United States)

    Mowarin, Macaulay

    2009-01-01

    This paper undertakes a detailed analysis of sentential negation in the English language with Chomsky's Government-Binding theory of Transformational Grammar as theoretical model. It distinguishes between constituent and sentential negation in English. The essay identifies the exact position of Negation phrase in an English clause structure. It…

  9. Negative ion sources

    International Nuclear Information System (INIS)

    Ishikawa, Junzo; Takagi, Toshinori

    1983-01-01

    Negative ion sources have been originally developed at the request of tandem electrostatic accelerators, and hundreds of nA to several μA negative ion current has been obtained so far for various elements. Recently, the development of large current hydrogen negative ion sources has been demanded from the standpoint of the heating by neutral particle beam injection in nuclear fusion reactors. On the other hand, the physical properties of negative ions are interesting in the thin film formation using ions. Anyway, it is the present status that the mechanism of negative ion action has not been so fully investigated as positive ions because the history of negative ion sources is short. In this report, the many mechanisms about the generation of negative ions proposed so far are described about negative ion generating mechanism, negative ion source plasma, and negative ion generation on metal surfaces. As a result, negative ion sources are roughly divided into two schemes, plasma extraction and secondary ion extraction, and the former is further classified into the PIG ion source and its variation and Duoplasmatron and its variation; while the latter into reflecting and sputtering types. In the second half of the report, the practical negative ion sources of each scheme are described. If the mechanism of negative ion generation will be investigated more in detail and the development will be continued under the unified know-how as negative ion sources in future, the development of negative ion sources with which large current can be obtained for any element is expected. (Wakatsuki, Y.)

  10. 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.

  11. 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...... common in certain social context or genres, while polemic negations are more likely to come up in other genres and social settings. Previous studies have shown a relation between articulatory prominence and register, which may further inform the analysis. Hence, the paper investigates how articulatory...... prominence and register may either work in concert or oppose each other with respect to the cues they provide for the interpretation....

  12. Factors that negatively influence consumption of traditionally ...

    African Journals Online (AJOL)

    Factors that negatively influence consumption of traditionally fermented milk ... in various countries of sub-Saharan Africa and a number of health benefits to human ... influence consumption of Mursik, a traditionally fermented milk product from ...

  13. Dietary whole-grain wheat increases intestinal levels of bifidobacteria in humans and bifidobacterial abundance is negatively correlated with the effect of fecal water on trans-epithelial resistance in vitro

    DEFF Research Database (Denmark)

    Christensen, Ellen Gerd; Licht, Tine Rask; Kristensen, M.

    Consumption of whole grain products are considered to have beneficial effects on human health including decreased risk of cardiovascular disease. However, effects on gut microbial composition have only been studied limitedly. We used quantitative PCR to determine changes in the gut bacterial...... composition in post-menopausal women following a 12-week energy restricted intervention with whole-grain wheat (WW, n=37) or refined wheat (RW, n=33). The WW intervention significantly increased the relative abundance of Bifidobacterium. Caco-2 cells were exposed to fecal water to determine effects...... of the bacterial community metabolites on the trans-epithelial resistance (TER). Fecal water increased TER independent of diet, indicating that commensal bacteria provide metabolites facilitating an increase in intestinal integrity. TER was unexpectedly found to be negatively correlated to the relative abundance...

  14. Differences in expression of the cancer stem cell marker aldehyde dehydrogenase 1 among estrogen receptor-positive/human epidermal growth factor receptor type 2-negative breast cancer cases with early, late, and no recurrence.

    Science.gov (United States)

    Miyoshi, Yuichiro; Shien, Tadahiko; Ogiya, Akiko; Ishida, Naoko; Yamazaki, Kieko; Horii, Rie; Horimoto, Yoshiya; Masuda, Norikazu; Yasojima, Hiroyuki; Inao, Touko; Osako, Tomofumi; Takahashi, Masato; Tomioka, Nobumoto; Endo, Yumi; Hosoda, Mitsuchika; Doihara, Hiroyoshi; Miyoshi, Shinichiro; Yamashita, Hiroko

    2016-07-02

    The significance of the expression of aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, for predicting the recurrence of estrogen receptor (ER)-positive/human epidermal growth factor receptor type 2 (HER2)-negative breast cancer is still poorly understood. The value of ALDH1 in predicting the time of recurrence remains unknown. In total, 184 patients with early distant recurrence, 134 patients with late distant recurrence, and 321 control patients without recurrence for more than 10 years after starting initial treatment for ER-positive/HER2-negative breast cancer, registered in 9 institutions, were analyzed. We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups. The relationship between ALDH1 expression and overall survival after recurrence was also evaluated in each group. The rates of ALDH1 expression positivity (more than 1 %) in the early, late, and no recurrence groups were 18.4 %, 13.4 %, and 8.4 %, respectively. ALDH1 expression correlated significantly with lymph node metastases (p = 0.048) and the Ki-67 labeling index (p factor independently predicting overall survival after the detection of recurrence (adjusted OR 1.451, 95 % CI 0.985-2.085, p = 0.059). Among patients with ER-positive/HER2-negative breast cancer, ALDH1 expression was more common in those with early recurrence, and this expression was found to be associated with a more aggressive breast cancer phenotype than that in the patients without recurrence. Further study is needed to clarify the prognostic significance of the heterogeneity of cancer stem cells and to confirm their role in resistance to chemotherapy.

  15. Negative Ion Density Fronts

    International Nuclear Information System (INIS)

    Igor Kaganovich

    2000-01-01

    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

  16. 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...

  17. A Modality Called 'Negation'

    NARCIS (Netherlands)

    Berto, F.

    2015-01-01

    I propose a comprehensive account of negation as a modal operator, vindicating a moderate logical pluralism. Negation is taken as a quantifier on worlds, restricted by an accessibility relation encoding the basic concept of compatibility. This latter captures the core meaning of the operator. While

  18. Negative thermal expansion materials

    International Nuclear Information System (INIS)

    Evans, J.S.O.

    1997-01-01

    The recent discovery of negative thermal expansion over an unprecedented temperature range in ZrW 2 O 8 (which contracts continuously on warming from below 2 K to above 1000 K) has stimulated considerable interest in this unusual phenomenon. Negative and low thermal expansion materials have a number of important potential uses in ceramic, optical and electronic applications. We have now found negative thermal expansion in a large new family of materials with the general formula A 2 (MO 4 ) 3 . Chemical substitution dramatically influences the thermal expansion properties of these materials allowing the production of ceramics with negative, positive or zero coefficients of thermal expansion, with the potential to control other important materials properties such as refractive index and dielectric constant. The mechanism of negative thermal expansion and the phase transitions exhibited by this important new class of low-expansion materials will be discussed. (orig.)

  19. 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

  20. Atomic negative ions

    International Nuclear Information System (INIS)

    Brage, T.

    1991-01-01

    We review some of the recent progress in the studies of alkaline-earth, negative ions. Computations of autodetachment rates, electron affinities and transition wavelengths are discussed and some new and improved results are given

  1. 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’.

  2. On Various Negative Translations

    Directory of Open Access Journals (Sweden)

    Gilda Ferreira

    2011-01-01

    Full Text Available Several proof translations of classical mathematics into intuitionistic mathematics have been proposed in the literature over the past century. These are normally referred to as negative translations or double-negation translations. Among those, the most commonly cited are translations due to Kolmogorov, Godel, Gentzen, Kuroda and Krivine (in chronological order. In this paper we propose a framework for explaining how these different translations are related to each other. More precisely, we define a notion of a (modular simplification starting from Kolmogorov translation, which leads to a partial order between different negative translations. In this derived ordering, Kuroda and Krivine are minimal elements. Two new minimal translations are introduced, with Godel and Gentzen translations sitting in between Kolmogorov and one of these new translations.

  3. Negative ion sourcery

    International Nuclear Information System (INIS)

    Os, C.F.A. van.

    1989-01-01

    The work described in this thesis is involved by current research programs in the field of nuclear-fusion. A brief introduction to fusion is given, anticipated problems related to current drive of the fusion plasma are pinpointed and probable suggestions to overcome these problems are described. One probable means for current drive is highlighted; Neutral Beam Injection (NBI). This is based on injecting a 1 MeV neutral hydrogen or deuterium beam into a fusion plasma. Negative ions are needed as primary particles because they can easily be neutralized at 1 MeV. The two current schemes for production of negative ions are described, volume production and negative surface ionization. The latter method is extensively studied in this thesis. (author). 171 refs.; 55 figs.; 7 tabs

  4. Benefit of adjuvant chemotherapy with or without trastuzumab in pT1ab node-negative human epidermal growth factor receptor 2-positive breast carcinomas: results of a national multi-institutional study.

    Science.gov (United States)

    de Nonneville, Alexandre; Gonçalves, Anthony; Zemmour, Christophe; Classe, Jean M; Cohen, Monique; Lambaudie, Eric; Reyal, Fabien; Scherer, Christophe; Muracciole, Xavier; Colombo, Pierre E; Giard, Sylvia; Rouzier, Roman; Villet, Richard; Chopin, Nicolas; Darai, Emile; Garbay, Jean R; Gimbergues, Pierre; Sabiani, Laura; Coutant, Charles; Sabatier, Renaud; Bertucci, François; Boher, Jean M; Houvenaeghel, Gilles

    2017-04-01

    Benefit of adjuvant trastuzumab-based chemotherapy for node-positive and/or >1 cm human epidermal growth factor receptor 2-positive (HER2+) breast carcinomas has been clearly demonstrated in randomized clinical trials. Yet, evidence that adjuvant chemotherapy with or without trastuzumab is effective in pT1abN0 HER2+ tumors is still limited. The primary objective of this study was to investigate the impact of adjuvant chemotherapy ± trastuzumab on outcome in this subpopulation. A total of 356 cases of pT1abN0M0 HER2 + breast cancers were retrospectively identified from a large cohort of 22,334 patients, including 1248 HER2+ patients who underwent primary surgery at 17 French centers, between December 1994 and January 2014. The primary end point was disease-free survival (DFS). A multivariate Cox model was built, including adjuvant chemotherapy, tumor size, hormone receptor status, and Scarff Bloom Richardson (SBR) grade. A total of 138 cases (39%) were treated with trastuzumab-based chemotherapy, 29 (8%) with chemotherapy alone, and 189 (53%) received neither trastuzumab nor chemotherapy. Adjuvant chemotherapy ± trastuzumab was associated with a significant DFS benefit (3-year 99 vs. 90%, and 5-year 96 vs. 84%, Hazard ratio, HR 0.26 [0.10-0.67]; p = 0.003, logrank test) which was maintained in multivariate analysis (HR 0.19 [0.07-0.52]; p = 0.001). Metastasis-free survival was also increased (HR 0.25 [0.07-0.86]; p = 0.018, logrank test) at 3-year (99 vs. 95%) and 5-year (98 vs. 89%) censoring. Exploratory subgroup analysis found DFS benefit to be significant in hormone receptor-negative, hormone receptor-positive, and pT1b tumors, but not in pT1a tumors. Adjuvant chemotherapy ± trastuzumab is associated with a significantly reduced risk of recurrence in subcentimeter node-negative HER2+ breast cancers. Most of the benefit may be driven by pT1b tumors.

  5. 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

  6. Relación entre el virus humano herpes 8 y el sarcoma de Kaposi en pacientes positivos y negativos para el VIH Relationship between human herpes virus 8 and Kaposi sarcomain HIV positive and negative patients

    Directory of Open Access Journals (Sweden)

    BEATRIZ OROZCO

    2007-09-01

    Full Text Available Introducción. Parece existir una relación de causalidad entre la infección por el virus humano herpes 8 ( human Herpesvirus 8, HHV-8 y el desarrollo de sarcoma de Kaposi, especialmente en la población positiva para virus de inmunodeficiencia humana (VIH. Objetivo. Fue determinar la relación entre los resultados serológicos positivos para HHV-8 y el sarcoma de Kaposi en pacientes positivos y negativos para VIH de Medellín, buscando la relación con distintas variables. Materiales y métodos. Es un estudio descriptivo, de cohorte, prospectivo, del suero de 98 pacientes de diferentes instituciones de salud de Medellín, los cuales se dividieron en cuatro grupos para determinar por inmunofluorescencia su seropositividad frente a HHV-8 y poder asociar en forma univariada y bivariada con diferentes variables. Resultados. Se estudiaron 98 sueros. En el grupo de pacientes con sarcoma de Kaposi y VIH, 83,3% fueron positivos para HHV- 8, en el grupo sin sarcoma de Kaposi pero con sífilis, 20,8% fueron positivos para HHV-8, en el grupo sin sarcoma de Kaposi pero VIH positivos, 8% fueron positivos para HHV-8 y en el grupo de sueros de banco de sangre, 4% fueron positivos para HHV-8. La presencia de sarcoma de Kaposi no tuvo relación con la evolución de la enfermedad por VIH ni con el recuento de CD4/ml. Conclusiones. El HHV-8 circula en nuestro medio y existe una relación entre la infección por este virus y el desarrollo de sarcoma de Kaposi, especialmente en pacientes con enfermedades de transmisión sexual y VIH positivos.Background: Apparently, there is a relationship between human Herpesvirus 8 (HHV-8 infection and Kaposi´ sarcoma, especially in HIV-positive population. Objectives: To define the relationship between seropositivity against HHV- 8 and Kaposi´ sarcoma in an HIV positive and negative population from Medellín, looking for its relationship with different variables. Methods: It is a descriptive, cohort, prospective study which

  7. 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.

  8. Dualising Intuitionictic Negation

    Directory of Open Access Journals (Sweden)

    Graham Priest

    2009-01-01

    Full Text Available One of Da Costa's motives when he constructed the paraconsistent logic Cw was to dualise the negation of intuitionistic logic. In this paper I explore a different way of going about this task. A logic is defined by taking the Kripke semantics for intuitionistic logic, and dualising the truth conditions for negation. Various properties of the logic are established, including its relation to CWo Tableau and natural deduction systems for the logic are produced, as are appropriate algebraic structures. The paper then investigates dualising the intuitionistic conditional in the same way. This establishes various connections between the logic, and a logic called in the literature 'Brouwerian logic' or 'closed-set logic'.

  9. Dualising Intuitionistic Negation

    Directory of Open Access Journals (Sweden)

    Graham Priest

    2009-08-01

    Full Text Available One of Da Costa’s motives when he constructed the paraconsistent logic C! was to dualise the negation of intuitionistic logic. In this paper I explore a different way of going about this task. A logic is defined by taking the Kripke semantics for intuitionistic logic, and dualising the truth conditions for negation. Various properties of the logic are established, including its relation to C!. Tableau and natural deduction systems for the logic are produced, as are appropriate algebraic structures. The paper then investigates dualising the intuitionistic conditional in the same way. This establishes various connections between the logic, and a logic called in the literature ‘Brouwerian logic’ or ‘closed-set logic’.

  10. Negative ion beam processes

    International Nuclear Information System (INIS)

    Hayward, T.D.; Lawrence, G.P.; Bentley, R.F.; Malanify, J.J.; Jackson, J.A.

    1975-06-01

    Los Alamos Scientific Laboratory fiscal year 1975 work on production of intense, very bright, negative hydrogen (H - ), ion beams and conversion of a high-energy (a few hundred MeV) negative beam into a neutral beam are described. The ion source work has used a cesium charge exchange source that has produced H - ion beams greater than or equal to 10 mA (about a factor of 10 greater than those available 1 yr ago) with a brightness of 1.4 x 10 9 A/m 2 -rad 2 (about 18 times brighter than before). The high-energy, neutral beam production investigations have included measurements of the 800-MeV H - -stripping cross section in hydrogen gas (sigma/sub -10/, tentatively 4 x 10 -19 cm 2 ), 3- to 6-MeV H - -stripping cross sections in a hydrogen plasma (sigma/sub -10/, tentatively 2 to 4 x 10 -16 cm 2 ), and the small-angle scattering that results from stripping an 800-MeV H - ion beam to a neutral (H 0 ) beam in hydrogen gas. These last measurements were interrupted by the Los Alamos Meson Physics Facility shutdown in December 1974, but should be completed early in fiscal year 1976 when the accelerator resumes operation. Small-angle scattering calculations have included hydrogen gas-stripping, plasma-stripping, and photodetachment. Calculations indicate that the root mean square angular spread of a 390-MeV negative triton (T - ) beam stripped in a plasma stripper may be as low as 0.7 μrad

  11. Estimating the Probability of Negative Events

    Science.gov (United States)

    Harris, Adam J. L.; Corner, Adam; Hahn, Ulrike

    2009-01-01

    How well we are attuned to the statistics of our environment is a fundamental question in understanding human behaviour. It seems particularly important to be able to provide accurate assessments of the probability with which negative events occur so as to guide rational choice of preventative actions. One question that arises here is whether or…

  12. 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...

  13. 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...

  14. Veillonella, Firmicutes: Microbes disguised as Gram negatives

    DEFF Research Database (Denmark)

    Vesth, Tammi Camilla; Ozen, Asli; Andersen, Sandra Christine

    2013-01-01

    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......, 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 (mainly) Gram positive phylum of the Firmicutes. Further studies are required to unveil the evolutionary history...

  15. 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.

  16. 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.

  17. Lithium alloy negative electrodes

    Science.gov (United States)

    Huggins, Robert A.

    The 1996 announcement by Fuji Photo Film of the development of lithium batteries containing convertible metal oxides has caused a great deal of renewed interest in lithium alloys as alternative materials for use in the negative electrode of rechargeable lithium cells. The earlier work on lithium alloys, both at elevated and ambient temperatures is briefly reviewed. Basic principles relating thermodynamics, phase diagrams and electrochemical properties under near-equilibrium conditions are discussed, with the Li-Sn system as an example. Second-phase nucleation, and its hindrance under dynamic conditions plays an important role in determining deviations from equilibrium behavior. Two general types of composite microstructure electrodes, those with a mixed-conducting matrix, and those with a solid electrolyte matrix, are discussed. The Li-Sn-Si system at elevated temperatures, and the Li-Sn-Cd at ambient temperatures are shown to be examples of mixed-conducting matrix microstructures. The convertible oxides are an example of the solid electrolyte matrix type. Although the reversible capacity can be very large in this case, the first cycle irreversible capacity required to convert the oxides to alloys may be a significant handicap.

  18. Microdosimetry of negative pions

    International Nuclear Information System (INIS)

    Amols, H.I.; Dicello, J.F.; Lane, T.F.

    1976-01-01

    The radiation quality of negative and positive pions of initial momentum 168MeV/c has been determined at eight different depths in a liquid phantom. The measurements were made with a 2.5cm diameter spherical proportional counter with Shonka A-150 neutron tissue equivalent plastic walls. The gas pressure in the sensitive volume was chosen to stimulate a diameter of 2μm in unit density material. Dose distributions as a function of lineal energy change slowly in the entrance and plateau regions with a dose mean lineal energy of 6-8keV/μm. Less than 3% of the dose is delivered in excess of 50keV/μm in this region. In the Bragg peak region the distributions change rapidly as a function of depth with the dose mean lineal energy increasing to 38keV/μm at the peak and to 57keV/μm just beyond the peak. On the basis of these microdosimetric data predictions of RBE and OER have been made with the use of both the theory of dual radiation action and also the delta ray theory of cell survival. The former has been used to predict biological response at low doses and the latter at high doses. A comparison is made between the two theories at intermediate doses. The results of these calculations are not inconsistant with recent biological data

  19. 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.

  20. Implementation of the Thin Layer Agar Method for Diagnosis of Smear-Negative Pulmonary Tuberculosis in a Setting with a High Prevalence of Human Immunodeficiency Virus Infection in Homa Bay, Kenya▿ †

    Science.gov (United States)

    Martin, Anandi; Munga Waweru, Peter; Babu Okatch, Fred; Amondi Ouma, Naureen; Bonte, Laurence; Varaine, Francis; Portaels, Françoise

    2009-01-01

    The objective of this study was to evaluate the performance of a low-cost method, the thin layer agar (TLA) method, for the diagnosis of smear-negative patients. This prospective study was performed in Homa Bay District Hospital in Kenya. Out of 1,584 smear-negative sputum samples, 212 (13.5%) were positive by culture in Löwenstein-Jensen medium (LJ) and 220 (14%) were positive by the TLA method. The sensitivities of LJ and TLA were 71% and 74%, respectively. TLA could become an affordable method for the diagnosis of smear-negative tuberculosis in resource-limited settings, with results available within 2 weeks. PMID:19494065

  1. 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

  2. Positive Effects of Negative Publicity: When Negative Reviews Increase Sales

    OpenAIRE

    Jonah Berger; Alan T. Sorensen; Scott J. Rasmussen

    2010-01-01

    Can negative information about a product increase sales, and if so, when? Although popular wisdom suggests that "any publicity is good publicity," prior research has demonstrated only downsides to negative press. Negative reviews or word of mouth, for example, have been found to hurt product evaluation and sales. Using a combination of econometric analysis and experimental methods, we unify these perspectives to delineate contexts under which negative publicity about a product will have posit...

  3. 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...

  4. Negative dimensional integrals. Pt. 1

    International Nuclear Information System (INIS)

    Halliday, I.G.; Ricotta, R.M.

    1987-01-01

    We propose a new method of evaluating integrals based on negative dimensional integration. We compute Feynman graphs by considering analytic extensions. Propagators are raised to negative integer powers and integrated over negative integer dimensions. We are left with the problem of computing polynomial integrals and summing finite series. (orig.)

  5. Negative chemical ionization mass spectrometry

    International Nuclear Information System (INIS)

    Smit, A.L.C.

    1979-01-01

    This thesis describes some aspects of Negative Chemical Ionization (NCI) mass spectrometry. The reasons for the growing interest in NCI are: (i) to extend the basic knowledge of negative ions and their reactions in the gas phase; (ii) to investigate whether or not this knowledge of negative ions can be used successfully to elucidate the structure of molecules by mass spectrometry. (Auth.)

  6. Thermodynamics of negative absolute pressures

    International Nuclear Information System (INIS)

    Lukacs, B.; Martinas, K.

    1984-03-01

    The authors show that the possibility of negative absolute pressure can be incorporated into the axiomatic thermodynamics, analogously to the negative absolute temperature. There are examples for such systems (GUT, QCD) processing negative absolute pressure in such domains where it can be expected from thermodynamical considerations. (author)

  7. 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.

  8. Negative snakes in JET: evidence for negative shear

    International Nuclear Information System (INIS)

    Gill, R.D.; Alper, B.; Edwards, A.W.

    1994-01-01

    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

  9. Positive rights, negative rights and health care.

    Science.gov (United States)

    Bradley, Andrew

    2010-12-01

    In the current debate about healthcare reform in the USA, advocates for government-ensured universal coverage assume that health care is a right. Although this position is politically popular, it is sometimes challenged by a restricted view of rights popular with libertarians and individualists. The restricted view of rights only accepts 'negative' rights as legitimate rights. Negative rights, the argument goes, place no obligations on you to provide goods to other people and thus respect your right to keep the fruits of your labour. A classic enumeration of negative rights includes life, liberty, and the pursuit of happiness. Positive rights, by contrast, obligate you either to provide goods to others, or pay taxes that are used for redistributive purposes. Health care falls into the category of positive rights since its provision by the government requires taxation and therefore redistribution. Therefore, the libertarian or individualist might argue that health care cannot be a true right. This paper rejects the distinction between positive and negative rights. In fact, the protection of both positive and negative rights can place obligations on others. Furthermore, because of its role in helping protect equality of opportunity, health care can be tied to the rights to life, liberty, and the pursuit of happiness. There is, therefore, good reason to believe that health care is a human right and that universal access should be guaranteed. The practical application, by governments and non-governmental organisations, of several of the arguments presented in this paper is also discussed.

  10. Negative Campaigning and the Logic of Retaliation in Multiparty Competition

    OpenAIRE

    Dolezal, Martin; Ennser-Jedenastik, Laurenz; M?ller, Wolfgang C.

    2016-01-01

    The extant literature has demonstrated that the logic of retaliation is a core feature of negative campaigning. Attacks by one side induce counterattacks by the other. Yet most research on the interactive nature of negative campaigning is limited to two-party competition and provides little theoretical justification for why political actors should respond to attacks with counterattacks. The present paper addresses these research gaps. We argue that the negativity bias in human information pro...

  11. 21 CFR 868.5935 - External negative pressure ventilator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false External negative pressure ventilator. 868.5935 Section 868.5935 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... ventilator. (a) Identification. An external negative pressure ventilator (e.g., iron lung, cuirass) is a...

  12. 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...... use Danish register data to find a signficant positive correlation between negative attitudes towards immigrants and high school attendance and find a positive impact of networking on high school attendance. In both the macro and the micro-econometric analysis we run the same regressions for natives...

  13. Negative hydrogen ion production mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Bacal, M. [UPMC, LPP, Ecole Polytechnique, UMR CNRS 7648, Palaiseau (France); Wada, M. [School of Science and Engineering, Doshisha University, Kyoto 610-0321 (Japan)

    2015-06-15

    Negative hydrogen/deuterium ions can be formed by processes occurring in the plasma volume and on surfaces facing the plasma. The principal mechanisms leading to the formation of these negative ions are dissociative electron attachment to ro-vibrationally excited hydrogen/deuterium molecules when the reaction takes place in the plasma volume, and the direct electron transfer from the low work function metal surface to the hydrogen/deuterium atoms when formation occurs on the surface. The existing theoretical models and reported experimental results on these two mechanisms are summarized. Performance of the negative hydrogen/deuterium ion sources that emerged from studies of these mechanisms is reviewed. Contemporary negative ion sources do not have negative ion production electrodes of original surface type sources but are operated with caesium with their structures nearly identical to volume production type sources. Reasons for enhanced negative ion current due to caesium addition to these sources are discussed.

  14. 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. We...... 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....

  15. Focusing on the negative: cultural differences in expressions of sympathy.

    Science.gov (United States)

    Koopmann-Holm, Birgit; Tsai, Jeanne L

    2014-12-01

    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 4 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 contain 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 feel 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 1 of 2 conditions: (a) to "push negative images away" (i.e., increasing desire to avoid negative affect) from or (b) to "pull negative images closer" (i.e., decreasing desire to avoid negative affect) to themselves. 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. positive). We discuss the

  16. 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...

  17. Simultaneous determination of phentermine and topiramate in human plasma by liquid chromatography-tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in pharmacokinetic study.

    Science.gov (United States)

    Ni, Yang; Zhou, Ying; Xu, Mingzhen; He, Xiaomeng; Li, Huqun; Haseeb, Satter; Chen, Hui; Li, Weiyong

    2015-03-25

    A new method for simultaneous determination of phentermine and topiramate by liquid chromatography/electrospray tandem mass spectrometry (LC/MS/MS) operated in positive and negative ionization switching modes was developed and validated. Protein precipitation with acetonitrile was selected for sample preparation. Analyses were performed on a liquid chromatography system employing a Kromasil 60-5CN column (2.1 mm × 100 mm, 5 μm) and an isocratic elution with mixed solution of acetonitrile-20mM ammonium formate containing 0.3% formic acid (40:60, v/v), at a flow rate of 0.35 mL/min. Doxazosin mesylate and pioglitazone were used as the internal standard (IS) respectively for quantification. The determination was carried out on an API 4000 triple-quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode using the following transitions monitored simultaneously: positive m/z 150.0/91.0 for phentermine, m/z 452.1/344.3 for doxazosin, and negative m/z 338.3/77.9 for topiramate, m/z 355.0/41.9 for pioglitazone. The method was validated to be linear over the concentration range of 1-800 ng mL(-1) for phentermine, 1-1000 ng mL(-1) for topiramate. Within- and between-day accuracy and precision of the validated method at three different concentration levels were within the acceptable limits of <15% at all concentrations. Blood samples were collected into heparinized tubes before and after administration. The simple and robust LC/MS/MS method was successfully applied for the simultaneous determination of phentermine and topiramate in a pharmacokinetic study in healthy male Chinese volunteers. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. 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.

  19. Isotropic Negative Thermal Expansion Metamaterials.

    Science.gov (United States)

    Wu, Lingling; Li, Bo; Zhou, Ji

    2016-07-13

    Negative thermal expansion materials are important and desirable in science and engineering applications. However, natural materials with isotropic negative thermal expansion are rare and usually unsatisfied in performance. Here, we propose a novel method to achieve two- and three-dimensional negative thermal expansion metamaterials via antichiral structures. The two-dimensional metamaterial is constructed with unit cells that combine bimaterial strips and antichiral structures, while the three-dimensional metamaterial is fabricated by a multimaterial 3D printing process. Both experimental and simulation results display isotropic negative thermal expansion property of the samples. The effective coefficient of negative thermal expansion of the proposed models is demonstrated to be dependent on the difference between the thermal expansion coefficient of the component materials, as well as on the circular node radius and the ligament length in the antichiral structures. The measured value of the linear negative thermal expansion coefficient of the three-dimensional sample is among the largest achieved in experiments to date. Our findings provide an easy and practical approach to obtaining materials with tunable negative thermal expansion on any scale.

  20. 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

  1. A morphological study of penile chancroid lesions in human immunodeficiency virus (HIV)-positive and -negative African men with a hypothesis concerning the role of chancroid in HIV transmission.

    Science.gov (United States)

    Magro, C M; Crowson, A N; Alfa, M; Nath, A; Ronald, A; Ndinya-Achola, J O; Nasio, J

    1996-10-01

    Chancroid, the most common cause of genital ulceration in Africa, is known to be associated epidemiologically with heterosexual transmission of human immunodeficiency virus (HIV). The pathophysiological mechanisms by which chancroid might facilitate the spread of HIV are obscure. To investigate the role of chancroid in HIV transmission, the authors studied the histological features of biopsies from 11 men with penile chancroid lesions including five who were serologically positive for HIV. The histomorphologic and immunophenotypic nature of the inflammatory infiltrates suggests that there is a significant role for cell-mediated immunity in the host response to Hemophilus ducreyi infection. This response may be critical to the role of chancroid in HIV transmission.

  2. Negative Attitudes, Network and Education

    DEFF Research Database (Denmark)

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

    , 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......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...... finds evidence that greater negative attitudes increase incentives for males to acquire education and that networking also increases immigrant education....

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

    International Nuclear Information System (INIS)

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

    2008-01-01

    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. 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. 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. 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

  4. Recent negative ion source developments

    International Nuclear Information System (INIS)

    Alton, G.D.

    1978-01-01

    This report describes recent results obtained from studies associated with the development of negative ion sources which utilize sputtering in a diffuse cesium plasma as a means of ion beam generation. Data are presented which relate negative ion yield and important operational parameters such as cesium oven temperature and sputter probe voltage from each of the following sources: (1) A source based in principle according to the University of Aarhus design and (2) an axial geometry source. The important design aspects of the sources are given--along with a list of the negative ion intensities observed to date. Also a qualitative description and interpretation of the negative ion generation mechanism in sources which utilize sputtering in the presence of cesium is given

  5. Ferroelectric Negative Capacitance Domain Dynamics

    OpenAIRE

    Hoffmann, Michael; Khan, Asif Islam; Serrao, Claudy; Lu, Zhongyuan; Salahuddin, Sayeef; Pešić, Milan; Slesazeck, Stefan; Schroeder, Uwe; Mikolajick, Thomas

    2017-01-01

    Transient negative capacitance effects in epitaxial ferroelectric Pb(Zr$_{0.2}$Ti$_{0.8}$)O$_3$ capacitors are investigated with a focus on the dynamical switching behavior governed by domain nucleation and growth. Voltage pulses are applied to a series connection of the ferroelectric capacitor and a resistor to directly measure the ferroelectric negative capacitance during switching. A time-dependent Ginzburg-Landau approach is used to investigate the underlying domain dynamics. The transien...

  6. 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.

  7. 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

    (AMHR2) and LHCGR, respectively, were observed for insLQ/insLQ compared to -/insLQ and the -/- genotypes. Moreover, LHCGR and CYP19a1 together with oestradiol and inhibin-B were significantly increased in -/insLQ compared to the -/- genotype. The homozygous insLQ genotype showed strong significant......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...... from 86 women undergoing fertility preservation. Analysis included hormonal profile of 297 follicular fluid (FF) samples and 148 corresponding granulosa cells samples were evaluated by qPCR for selected genes. Significantly reduced and non-detectable mRNA levels of anti-Müllerian hormone receptor II...

  8. Ferroelectric negative capacitance domain dynamics

    Science.gov (United States)

    Hoffmann, Michael; Khan, Asif Islam; Serrao, Claudy; Lu, Zhongyuan; Salahuddin, Sayeef; Pešić, Milan; Slesazeck, Stefan; Schroeder, Uwe; Mikolajick, Thomas

    2018-05-01

    Transient negative capacitance effects in epitaxial ferroelectric Pb(Zr0.2Ti0.8)O3 capacitors are investigated with a focus on the dynamical switching behavior governed by domain nucleation and growth. Voltage pulses are applied to a series connection of the ferroelectric capacitor and a resistor to directly measure the ferroelectric negative capacitance during switching. A time-dependent Ginzburg-Landau approach is used to investigate the underlying domain dynamics. The transient negative capacitance is shown to originate from reverse domain nucleation and unrestricted domain growth. However, with the onset of domain coalescence, the capacitance becomes positive again. The persistence of the negative capacitance state is therefore limited by the speed of domain wall motion. By changing the applied electric field, capacitor area or external resistance, this domain wall velocity can be varied predictably over several orders of magnitude. Additionally, detailed insights into the intrinsic material properties of the ferroelectric are obtainable through these measurements. A new method for reliable extraction of the average negative capacitance of the ferroelectric is presented. Furthermore, a simple analytical model is developed, which accurately describes the negative capacitance transient time as a function of the material properties and the experimental boundary conditions.

  9. Hormonal therapy followed by chemotherapy or the reverse sequence as first-line treatment of hormone-responsive, human epidermal growth factor receptor-2 negative metastatic breast cancer patients: results of an observational study.

    Science.gov (United States)

    Bighin, Claudia; Dozin, Beatrice; Poggio, Francesca; Ceppi, Marcello; Bruzzi, Paolo; D'Alonzo, Alessia; Levaggi, Alessia; Giraudi, Sara; Lambertini, Matteo; Miglietta, Loredana; Vaglica, Marina; Fontana, Vincenzo; Iacono, Giuseppina; Pronzato, Paolo; Del Mastro, Lucia

    2017-07-04

    Introduction Although hormonal-therapy is the preferred first-line treatment for hormone-responsive, HER2 negative metastatic breast cancer, no data from clinical trials support the choice between hormonal-therapy and chemotherapy.Methods Patients were divided into two groups according to the treatment: chemotherapy or hormonal-therapy. Outcomes in terms of clinical benefit and median overall survival (OS) were retrospectively evaluated in the two groups. To calculate the time spent in chemotherapy with respect to OS in the two groups, the proportion of patients in chemotherapy relative to those present in either group was computed at every day from the start of therapy.Results From 1999 to 2013, 119 patients received first-line hormonal-therapy (HT-first group) and 100 first-line chemotherapy (CT-first group). Patients in the CT-first group were younger and with poorer prognostic factors as compared to those in HT-first group. Clinical benefit (77 vs 81%) and median OS (50.7 vs 51.1 months) were similar in the two groups. Time spent in chemotherapy was significantly longer during the first 3 years in CT-first group (54-34%) as compared to the HT-first group (11-18%). This difference decreased after the third year and overall was 28% in the CT-first group and 18% in the HT-first group.Conclusions The sequence first-line chemotherapy followed by hormonal-therapy, as compared with the opposite sequence, is associated with a longer time of OS spent in chemotherapy. However, despite the poorer prognostic factors, patients in the CT-first group had a superimposable OS than those in the HT-first group.

  10. 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.

  11. Motion sickness: a negative reinforcement model.

    Science.gov (United States)

    Bowins, Brad

    2010-01-15

    Theories pertaining to the "why" of motion sickness are in short supply relative to those detailing the "how." Considering the profoundly disturbing and dysfunctional symptoms of motion sickness, it is difficult to conceive of why this condition is so strongly biologically based in humans and most other mammalian and primate species. It is posited that motion sickness evolved as a potent negative reinforcement system designed to terminate motion involving sensory conflict or postural instability. During our evolution and that of many other species, motion of this type would have impaired evolutionary fitness via injury and/or signaling weakness and vulnerability to predators. The symptoms of motion sickness strongly motivate the individual to terminate the offending motion by early avoidance, cessation of movement, or removal of oneself from the source. The motion sickness negative reinforcement mechanism functions much like pain to strongly motivate evolutionary fitness preserving behavior. Alternative why theories focusing on the elimination of neurotoxins and the discouragement of motion programs yielding vestibular conflict suffer from several problems, foremost that neither can account for the rarity of motion sickness in infants and toddlers. The negative reinforcement model proposed here readily accounts for the absence of motion sickness in infants and toddlers, in that providing strong motivation to terminate aberrant motion does not make sense until a child is old enough to act on this motivation.

  12. Human muscle cells express a B7-related molecule, B7-H1, with strong negative immune regulatory potential: a novel mechanism of counterbalancing the immune attack in idiopathic inflammatory myopathies.

    Science.gov (United States)

    Wiendl, Heinz; Mitsdoerffer, Meike; Schneider, Dagmar; Chen, Lieping; Lochmüller, Hanns; Melms, Arthur; Weller, Michael

    2003-10-01

    B7-H1 is a novel B7 family protein attributed to costimulatory and immune regulatory functions. Here we report that human myoblasts cultured from control subjects and patients with inflammatory myopathies as well as TE671 muscle rhabdomyosarcoma cells express high levels of B7-H1 after stimulation with the inflammatory cytokine IFN-gamma. Coculture experiments of MHC class I/II-positive myoblasts with CD4 and CD8 T cells in the presence of antigen demonstrated the functional consequences of muscle-related B7-H1 expression: production of inflammatory cytokines, IFN-gamma and IL-2, by CD4 as well CD8 T cells was markedly enhanced in the presence of a neutralizing anti-B7-H1 antibody. This observation was paralleled by an augmented expression of the T cell activation markers CD25, ICOS, and CD69, thus showing B7-H1-mediated inhibition of T cell activation. Further, we investigated 23 muscle biopsy specimens from patients with polymyositis (PM), inclusion body myositis (IBM), dermatomyositis (DM), and nonmyopathic controls for B7-H1 expression by immunohistochemistry: B7-H1 was expressed in PM, IBM, and DM specimens but not in noninflammatory and nonmyopathic controls. Staining was predominantly localized to areas of strong inflammation and to muscle cells as well as mononuclear cells. These data highlight the immune regulatory properties of muscle cells and suggest that B7-H1 expression represents an inhibitory mechanism induced upon inflammatory stimuli and aimed at protecting muscle fibers from immune aggression.

  13. Simultaneous determination of ten antiepileptic drugs in human plasma by liquid chromatography and tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in therapeutic drug monitoring.

    Science.gov (United States)

    Yin, Lei; Wang, Tingting; Shi, Meiyun; Zhang, Ying; Zhao, Xiaojun; Yang, Yan; Gu, Jingkai

    2016-03-01

    A simple, rapid, and high-throughput liquid chromatography with tandem mass spectrometry method for the simultaneous quantitation of ten antiepileptic drugs in human plasma has been developed and validated. The method required only 10 μL of plasma. After simple protein precipitation using acetonitrile, the analytes and internal standard diphenhydramine were separated on a Zorbax SB-C18 column (50 × 4.6 mm, 2.7 μm) using acetonitrile/water as the mobile phase at a flow rate of 0.9 mL/min. The total run time was 6 min for each sample. The validation results of specificity, matrix effects, recovery, linearity, precision, and accuracy were satisfactory. The lower limit of quantification was 0.04 μg/mL for carbamazepine, 0.02 μg/mL for lamotrigine, 0.01 μg/mL for oxcarbazepine, 0.4 μg/mL for 10-hydroxycarbazepine, 0.1 μg/mL for carbamazepine-10,11-epoxide, 0.15 μg/mL for levetiracetam, 0.06 μg/mL for phenytoin, 0.3 μg/mL for valproic acid, 0.03 μg/mL for topiramate, and 0.15 μg/mL for phenobarbital. The intraday precision and interday precision were less than 7.6%, with the accuracy ranging between -8.1 and 7.9%. The method was successfully applied to therapeutic drug monitoring of 1237 patients with epilepsy after administration of standard antiepileptic drugs. The method has been proved to meet the high-throughput requirements in therapeutic drug monitoring. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Quantum entanglement at negative temperature

    International Nuclear Information System (INIS)

    Furman, G B; Meerovich, V M; Sokolovsky, V L

    2013-01-01

    An isolated spin system that is in internal thermodynamic equilibrium and that has an upper limit to its allowed energy states can possess a negative temperature. We calculate the thermodynamic characteristics and the concurrence in this system over the entire range of positive and negative temperatures. Our calculation was performed for different real structures, which can be used in experiments. It is found that the temperature dependence of the concurrence is substantially asymmetrical similarly to other thermodynamic characteristics. At a negative temperature the maximum concurrence and the absolute temperature of the entanglement appearance are significantly larger than those at a positive temperature. The concurrence can be characterized by two dimensionless parameters: the ratio between the Zeeman and dipolar energies and the ratio of the thermal and dipolar energies. It was shown that for all considered structures the dimensionless temperatures of the transition between entanglement and separability of the first and second spins are independent of spin structure and the number of spins. (paper)

  15. Negativity Bias in Dangerous Drivers.

    Directory of Open Access Journals (Sweden)

    Jing Chai

    Full Text Available The behavioral and cognitive characteristics of dangerous drivers differ significantly from those of safe drivers. However, differences in emotional information processing have seldom been investigated. Previous studies have revealed that drivers with higher anger/anxiety trait scores are more likely to be involved in crashes and that individuals with higher anger traits exhibit stronger negativity biases when processing emotions compared with control groups. However, researchers have not explored the relationship between emotional information processing and driving behavior. In this study, we examined the emotional information processing differences between dangerous drivers and safe drivers. Thirty-eight non-professional drivers were divided into two groups according to the penalty points that they had accrued for traffic violations: 15 drivers with 6 or more points were included in the dangerous driver group, and 23 drivers with 3 or fewer points were included in the safe driver group. The emotional Stroop task was used to measure negativity biases, and both behavioral and electroencephalograph data were recorded. The behavioral results revealed stronger negativity biases in the dangerous drivers than in the safe drivers. The bias score was correlated with self-reported dangerous driving behavior. Drivers with strong negativity biases reported having been involved in mores crashes compared with the less-biased drivers. The event-related potentials (ERPs revealed that the dangerous drivers exhibited reduced P3 components when responding to negative stimuli, suggesting decreased inhibitory control of information that is task-irrelevant but emotionally salient. The influence of negativity bias provides one possible explanation of the effects of individual differences on dangerous driving behavior and traffic crashes.

  16. 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...... and indications that quality of networks seems to matter more for immigrants than the quantity of individuals in a potential network....

  17. Patch Test Negative Generalized Dermatitis.

    Science.gov (United States)

    Spiker, Alison; Mowad, Christen

    2016-01-01

    Allergic contact dermatitis is a common condition in dermatology. Patch testing is the criterion standard for diagnosis. However, dermatitis is not always caused by an allergen, and patch testing does not identify a culprit in every patient. Generalized dermatitis, defined as eczematous dermatitis affecting greater than 3 body sites, is often encountered in dermatology practice, especially patch test referral centers. Management for patients with generalized dermatitis who are patch test negative is challenging. The purpose of this article is to outline an approach to this challenging scenario and summarize the paucity of existing literature on patch test negative generalized dermatitis.

  18. 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

  19. Negative energy solutions and symmetries

    International Nuclear Information System (INIS)

    Sidharth, B.G.

    2011-01-01

    We revisit the negative energy solutions of the Dirac (and Klein–Gordon) equation, which become relevant at very high energies in the context of the Feshbach–Villars formulation, and study several symmetries which follow therefrom. Significant consequences are briefly examined. (author)

  20. Symmetric relations of finite negativity

    NARCIS (Netherlands)

    Kaltenbaeck, M.; Winkler, H.; Woracek, H.; Forster, KH; Jonas, P; Langer, H

    2006-01-01

    We construct and investigate a space which is related to a symmetric linear relation S of finite negativity on an almost Pontryagin space. This space is the indefinite generalization of the completion of dom S with respect to (S.,.) for a strictly positive S on a Hilbert space.

  1. Production of negative helium ions

    International Nuclear Information System (INIS)

    Toledo, A.S. de; Sala, O.

    1977-01-01

    A negative helium ion source using potassium charge exchange vapor has been developed to be used as an injector for the Pelletron accelerator. 3 He and α beam currents of up to 2μA have been extracted with 75% particle transmission through the machine [pt

  2. 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. ...

  3. Unimode metamaterials exhibiting negative linear compressibility and negative thermal expansion

    International Nuclear Information System (INIS)

    Dudek, Krzysztof K; Attard, Daphne; Caruana-Gauci, Roberto; Grima, Joseph N; Wojciechowski, Krzysztof W

    2016-01-01

    Unimode metamaterials made from rotating rigid triangles are analysed mathematically for their mechanical and thermal expansion properties. It is shown that these unimode systems exhibit positive Poisson’s ratios irrespective of size, shape and angle of aperture, with the Poisson’s ratio exhibiting giant values for certain conformations. When the Poisson’s ratio in one loading direction is larger than +1, the systems were found to exhibit the anomalous property of negative linear compressibility along this direction, that is, the systems expand in this direction when hydrostatically compressed. Also discussed are the thermal expansion properties of these systems under the assumption that the units exhibit increased rotational agitation once subjected to an increase in temperature. The effect of the geometric parameters on the aforementioned thermo-mechanical properties of the system, are discussed, with the aim of identifying negative behaviour. (paper)

  4. 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

  5. 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.

  6. 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...... a randomised controlled trial in two tertiary and three teaching hospitals in three regions of Denmark, the Happy Belly Study, investigating the effectiveness of iNPWT in a population of obese women after caesarean section. The Happy Belly Study has demonstrated that prophylactic iNPWT significantly reduced...

  7. Perfect antireflection via negative refraction

    International Nuclear Information System (INIS)

    Monzon, Juan J.; Barriuso, Alberto G.; Sanchez-Soto, Luis L.

    2006-01-01

    We suggest a geometrical framework to discuss the action of slabs of negatively refracting materials. We show that these slabs generate the same orbits as normal materials, but traced out in opposite directions. This property allows us to confirm that the action of any lossless multilayer can be optically canceled by putting it together with the multilayer constructed as the inverted mirror image, with ε and μ reversed in sign

  8. Negative ion detachment cross sections

    International Nuclear Information System (INIS)

    Champion, R.L.; Doverspike, L.D.

    1992-10-01

    The authors have measured absolute cross sections for electron detachment and charge exchange for collision of O and S with atomic hydrogen, have investigated the sputtering and photodesorption of negative ions from gas covered surfaces, and have begun an investigation of photon-induced field emission of electrons from exotic structures. Brief descriptions of these activities as well as future plans for these projects are given below

  9. Weak negation in inquisitive semantics

    Czech Academy of Sciences Publication Activity Database

    Punčochář, Vít

    2015-01-01

    Roč. 24, č. 3 (2015), s. 323-355 ISSN 0925-8531 R&D Projects: GA ČR(CZ) GA13-21076S Institutional support: RVO:67985955 Keywords : inquisitive semantics * negation * possible worlds * Fitch-style natural deduction * denial Subject RIV: AA - Philosophy ; Religion Impact factor: 0.450, year: 2015 http://link.springer.com/article/10.1007%2Fs10849-015-9219-2

  10. Negative-Pressure Pulmonary Edema.

    Science.gov (United States)

    Bhattacharya, Mallar; Kallet, Richard H; Ware, Lorraine B; Matthay, Michael A

    2016-10-01

    Negative-pressure pulmonary edema (NPPE) or postobstructive pulmonary edema is a well-described cause of acute respiratory failure that occurs after intense inspiratory effort against an obstructed airway, usually from upper airway infection, tumor, or laryngospasm. Patients with NPPE generate very negative airway pressures, which augment transvascular fluid filtration and precipitate interstitial and alveolar edema. Pulmonary edema fluid collected from most patients with NPPE has a low protein concentration, suggesting hydrostatic forces as the primary mechanism for the pathogenesis of NPPE. Supportive care should be directed at relieving the upper airway obstruction by endotracheal intubation or cricothyroidotomy, institution of lung-protective positive-pressure ventilation, and diuresis unless the patient is in shock. Resolution of the pulmonary edema is usually rapid, in part because alveolar fluid clearance mechanisms are intact. In this review, we discuss the clinical presentation, pathophysiology, and management of negative-pressure or postobstructive pulmonary edema. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  11. Nosewitness Identification: Effects of Negative Emotion

    Science.gov (United States)

    Ferreira, Jacqueline; Rocha, Marta; Silva, Carlos F.; Olsson, Mats J.

    2015-01-01

    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. PMID:25612211

  12. Human immunodeficiency virus negative Kaposi sarcoma and lymphoproliferative disorders

    NARCIS (Netherlands)

    Fossati, S; Boneschi, [No Value; Ferrucci, S; Brambilla, L

    1999-01-01

    BACKGROUND. The concomitant occurrence of more than one primary neoplasm in the same individual has led researchers to seek possible common etiopathogenetic factors. Kaposi sarcoma (KS) is a multicentric neoplasm of vascular origin and perhaps viral etiology. Four forms of KS are known: classic or

  13. Underpowered samples, false negatives, and unconscious learning.

    Science.gov (United States)

    Vadillo, Miguel A; Konstantinidis, Emmanouil; Shanks, David R

    2016-02-01

    The scientific community has witnessed growing concern about the high rate of false positives and unreliable results within the psychological literature, but the harmful impact of false negatives has been largely ignored. False negatives are particularly concerning in research areas where demonstrating the absence of an effect is crucial, such as studies of unconscious or implicit processing. Research on implicit processes seeks evidence of above-chance performance on some implicit behavioral measure at the same time as chance-level performance (that is, a null result) on an explicit measure of awareness. A systematic review of 73 studies of contextual cuing, a popular implicit learning paradigm, involving 181 statistical analyses of awareness tests, reveals how underpowered studies can lead to failure to reject a false null hypothesis. Among the studies that reported sufficient information, the meta-analytic effect size across awareness tests was d z = 0.31 (95 % CI 0.24-0.37), showing that participants' learning in these experiments was conscious. The unusually large number of positive results in this literature cannot be explained by selective publication. Instead, our analyses demonstrate that these tests are typically insensitive and underpowered to detect medium to small, but true, effects in awareness tests. These findings challenge a widespread and theoretically important claim about the extent of unconscious human cognition.

  14. 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.

  15. Perfect imaging without negative refraction

    OpenAIRE

    Leonhardt, Ulf

    2009-01-01

    Perfect imaging has been believed to rely on negative refraction, but here we show that an ordinary positively-refracting optical medium may form perfect images as well. In particular, we establish a mathematical proof that Maxwell's fish eye in two-dimensional integrated optics makes a perfect instrument with a resolution not limited by the wavelength of light. We also show how to modify the fish eye such that perfect imaging devices can be made in practice. Our method of perfect focusing ma...

  16. Perfect imaging without negative refraction

    Energy Technology Data Exchange (ETDEWEB)

    Leonhardt, Ulf [School of Physics and Astronomy, University of St Andrews, North Haugh, St Andrews KY16 9SS (United Kingdom)], E-mail: ulf@st-andrews.ac.uk

    2009-09-15

    Perfect imaging has been believed to rely on negative refraction, but here we show that an ordinary positively refracting optical medium may form perfect images as well. In particular, we establish a mathematical proof that Maxwell's fish eye in two-dimensional (2D) integrated optics makes a perfect instrument with a resolution not limited by the wavelength of light. We also show how to modify the fish eye such that perfect imaging devices can be made in practice. Our method of perfect focusing may also find applications outside of optics, in acoustics, fluid mechanics or quantum physics, wherever waves obey the 2D Helmholtz equation.

  17. Imagery mismatch negativity in musicians.

    Science.gov (United States)

    Herholz, Sibylle C; Lappe, Claudia; Knief, Arne; Pantev, Christo

    2009-07-01

    The present study investigated musical imagery in musicians and nonmusicians by means of magnetoencephalography (MEG). We used a new paradigm in which subjects had to continue familiar melodies in their mind and then judged if a further presented tone was a correct continuation of the melody. Incorrect tones elicited an imagery mismatch negativity (iMMN) in musicians but not in nonmusicians. This finding suggests that the MMN component can be based on an imagined instead of a sensory memory trace and that imagery of music is modulated by musical expertise.

  18. Negative mass solitons in gravity

    International Nuclear Information System (INIS)

    Cebeci, Hakan; Sarioglu, Oezguer; Tekin, Bayram

    2006-01-01

    We first reconstruct the conserved (Abbott-Deser) charges in the spin-connection formalism of gravity for asymptotically (Anti)-de Sitter spaces, and then compute the masses of the AdS soliton and the recently found Eguchi-Hanson solitons in generic odd dimensions, unlike the previous result obtained for only five dimensions. These solutions have negative masses compared to the global AdS or AdS/Z p spacetimes. As a separate note, we also compute the masses of the recent even dimensional Taub-NUT-Reissner-Nordstroem metrics

  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 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 missed by primary HPV screening. Cancer Cytopathol 2017;125:795-805. © 2017 American Cancer Society. © 2017 American Cancer Society.

  20. Triple-negative breast cancer: present challenges and new perspectives

    NARCIS (Netherlands)

    Podo, Franca; Buydens, Lutgarde M. C.; Degani, Hadassa; Hilhorst, Riet; Klipp, Edda; Gribbestad, Ingrid S.; van Huffel, Sabine; van Laarhoven, Hanneke W. M.; Luts, Jan; Monleon, Daniel; Postma, Geert J.; Schneiderhan-Marra, Nicole; Santoro, Filippo; Wouters, Hans; Russnes, Hege G.; Sørlie, Therese; Tagliabue, Elda; Børresen-Dale, Anne-Lise

    2010-01-01

    Triple-negative breast cancers (TNBC), characterized by absence of estrogen receptor (ER), progesterone receptor (PR) and lack of overexpression of human epidermal growth factor receptor 2 (HER2), are typically associated with poor prognosis, due to aggressive tumor phenotype(s), only partial

  1. Optimization of negative ion accelerators

    International Nuclear Information System (INIS)

    Pamela, J.

    1991-01-01

    We have started to study negative ion extraction and acceleration systems in view of designing a 1 MeV D - accelerator. This study is being made with a two-Dimensional code that has been specifically developed in our laboratory and validated by comparison to three sets of experimental data. We believe that the criteria for negative ion accelerator design optimization should be: (i) to provide the best optics; (ii) to reduce the power load on the extraction grid; (iii) to allow operation with low electric fields in order to reduce the problem of breakdowns. We show some results of optics calculations performed for two systems that will be operational in the next months: the CEA-JAERI collaboration at Cadarache and the european DRAGON experiment at Culham. Extrapolations to higher energies of 500 to 1100 keV have also been conducted. All results indicate that the overall accelerator length, whatever be the number of gaps, is constrained by space charge effects (Child-Langmuir). We have combined this constraint with high-voltage hold-off empirical laws. As a result, it appears that accelerating 10 mA/cm 2 of D - at 1 MeV with good optics, as required for NET or ITER, is close to the expected limit of high-voltage hold-off

  2. 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.

  3. 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…

  4. Coinductive Logic Programming with Negation

    Science.gov (United States)

    Min, Richard; Gupta, Gopal

    We introduce negation into coinductive logic programming (co-LP) via what we term Coinductive SLDNF (co-SLDNF) resolution. We present declarative and operational semantics of co-SLDNF resolution and present their equivalence under the restriction of rationality. Co-LP with co-SLDNF resolution provides a powerful, practical and efficient operational semantics for Fitting's Kripke-Kleene three-valued logic with restriction of rationality. Further, applications of co-SLDNF resolution are also discussed and illustrated where Co-SLDNF resolution allows one to develop elegant implementations of modal logics. Moreover it provides the capability of non-monotonic inference (e.g., predicate Answer Set Programming) that can be used to develop novel and effective first-order modal non-monotonic inference engines.

  5. 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

  6. Entanglement negativity in the multiverse

    Energy Technology Data Exchange (ETDEWEB)

    Kanno, Sugumi [Department of Theoretical Physics and History of Science, University of the Basque Country UPV/EHU, 48080 Bilbao (Spain); Shock, Jonathan P. [Laboratory for Quantum Gravity and Strings and Astrophysics, Cosmology and Gravity Center, Department of Mathematics and Applied Mathematics, University of Cape Town, Private Bag, Rondebosch 7701 (South Africa); Soda, Jiro, E-mail: sugumi.kanno@ehu.es, E-mail: jonathan.shock@uct.ac.za, E-mail: jiro@phys.sci.kobe-u.ac.jp [Department of Physics, Kobe University, Kobe 657-8501 (Japan)

    2015-03-01

    We explore quantum entanglement between two causally disconnected regions in the multiverse. We first consider a free massive scalar field, and compute the entanglement negativity between two causally separated open charts in de Sitter space. The qualitative feature of it turns out to be in agreement with that of the entanglement entropy. We then introduce two observers who determine the entanglement between two causally disconnected de Sitter spaces. When one of the observers remains constrained to a region of the open chart in a de Sitter space, we find that the scale dependence enters into the entanglement. We show that a state which is initially maximally entangled becomes more entangled or less entangled on large scales depending on the mass of the scalar field and recovers the initial entanglement in the small scale limit. We argue that quantum entanglement may provide some evidence for the existence of the multiverse.

  7. Entanglement negativity in the multiverse

    International Nuclear Information System (INIS)

    Kanno, Sugumi; Shock, Jonathan P.; Soda, Jiro

    2015-01-01

    We explore quantum entanglement between two causally disconnected regions in the multiverse. We first consider a free massive scalar field, and compute the entanglement negativity between two causally separated open charts in de Sitter space. The qualitative feature of it turns out to be in agreement with that of the entanglement entropy. We then introduce two observers who determine the entanglement between two causally disconnected de Sitter spaces. When one of the observers remains constrained to a region of the open chart in a de Sitter space, we find that the scale dependence enters into the entanglement. We show that a state which is initially maximally entangled becomes more entangled or less entangled on large scales depending on the mass of the scalar field and recovers the initial entanglement in the small scale limit. We argue that quantum entanglement may provide some evidence for the existence of the multiverse

  8. Entanglement negativity in the multiverse

    Energy Technology Data Exchange (ETDEWEB)

    Kanno, Sugumi [Department of Theoretical Physics and History of Science, University of the Basque Country UPV/EHU, 48080 Bilbao (Spain); IKERBASQUE, Basque Foundation for Science, Maria Diaz de Haro 3, 48013, Bilbao (Spain); Laboratory for Quantum Gravity & Strings and Astrophysics, Cosmology & Gravity Center, Department of Mathematics & Applied Mathematics, University of Cape Town, Private Bag, Rondebosch 7701 (South Africa); Shock, Jonathan P. [Laboratory for Quantum Gravity & Strings and Astrophysics, Cosmology & Gravity Center, Department of Mathematics & Applied Mathematics, University of Cape Town, Private Bag, Rondebosch 7701 (South Africa); National Institute for Theoretical Physics, Private Bag X1, Matieland, 7602 (South Africa); Soda, Jiro [Department of Physics, Kobe University, Kobe 657-8501 (Japan)

    2015-03-10

    We explore quantum entanglement between two causally disconnected regions in the multiverse. We first consider a free massive scalar field, and compute the entanglement negativity between two causally separated open charts in de Sitter space. The qualitative feature of it turns out to be in agreement with that of the entanglement entropy. We then introduce two observers who determine the entanglement between two causally disconnected de Sitter spaces. When one of the observers remains constrained to a region of the open chart in a de Sitter space, we find that the scale dependence enters into the entanglement. We show that a state which is initially maximally entangled becomes more entangled or less entangled on large scales depending on the mass of the scalar field and recovers the initial entanglement in the small scale limit. We argue that quantum entanglement may provide some evidence for the existence of the multiverse.

  9. Negative meson capture in hydrogen

    International Nuclear Information System (INIS)

    Baird, T.J.

    1977-01-01

    The processes of deexcitation and capture of negative mesons and hadrons in atomic hydrogen are investigated. Only slow collisions in which the projectile-atom relative velocity is less than one atomic unit are considered, and the motion of the incident particle is treated classically. For each classical trajectory the probability of ionizing the hydrogen atom is determined, together with the energy spectrum of the emitted electron. Ionization probabilities are calculated using the time-dependent formulation of the perturbed stationary state method. Exact two-center electronic wave functions are used for both bound and continuum states. The total ionization cross section and electron energy spectrum have been calculated for negative muons, kaons and antiprotons at incident relative velocities between 0.04 and 1.0 atomic units. The electron energy spectrum has a sharp peak for electron kinetic energies on the order of 10 -3 Rydbergs. The ionization process thus favors the emission of very slow electrons. The cross section for ionization with capture of the incident particle was calculated for relative kinetic energies greater than 1.0 Rydberg. Since ionization was found to occur with the emission of electrons of nearly zero kinetic energy, the fraction of ionizing collisions which result in capture decreases very rapidly with projectile kinetic energy. The energy distributions of slowed down muons and hadrons were also computed. These distributions were used together with the capture cross section to determine the distribution of kinetic energies at which capture takes place. It was found that most captures occur for kinetic energies slightly less than 1.0 Rydbergs with relatively little capture at thermal energies. The captured particles therefore tend to go into very large and loosely found orbits with binding energies less than 0.1 Rydbergs

  10. 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....... The technique of the proof is subsequently applied to show that every compact manifold of negative type must have trivial fundamental group, and to obtain a necessary criterion for product manifolds to be of negative type....

  11. Negative numbers and antimatter particles

    International Nuclear Information System (INIS)

    Tsan, Ung Chan

    2012-01-01

    Dirac's equation states that an electron implies the existence of an antielectron with the same mass (more generally same arithmetic properties) and opposite charge (more generally opposite algebraic properties). Subsequent observation of antielectron validated this concept. This statement can be extended to all matter particles; observation of antiproton, antineutron, antideuton … is in complete agreement with this view. Recently antihypertriton was observed and 38 atoms of antihydrogen were trapped. This opens the path for use in precise testing of nature's fundamental symmetries. The symmetric properties of a matter particle and its mirror antimatter particle seem to be well established. Interactions operate on matter particles and antimatter particles as well. Conservation of matter parallels addition operating on positive and negative numbers. Without antimatter particles, interactions of the Standard Model (electromagnetism, strong interaction and weak interaction) cannot have the structure of group. Antimatter particles are characterized by negative baryonic number A or/and negative leptonic number L. Materialization and annihilation obey conservation of A and L (associated to all known interactions), explaining why from pure energy (A = 0, L = 0) one can only obtain a pair of matter particle antimatter particle — electron antielectron, proton and antiproton — via materialization where the mass of a pair of particle antiparticle gives back to pure energy with annihilation. These two mechanisms cannot change the difference in the number of matter particles and antimatter particles. Thus from pure energy only a perfectly symmetric (in number) universe could be generated as proposed by Dirac but observation showed that our universe is not symmetric, it is a matter universe which is nevertheless neutral. Fall of reflection symmetries shattered the prejudice that there is no way to define in an absolute way right and left or matter and antimatter

  12. Emotionally negative pictures increase attention to a subsequent auditory stimulus.

    Science.gov (United States)

    Tartar, Jaime L; de Almeida, Kristen; McIntosh, Roger C; Rosselli, Monica; Nash, Allan J

    2012-01-01

    Emotionally negative stimuli serve as a mechanism of biological preparedness to enhance attention. We hypothesized that emotionally negative stimuli would also serve as motivational priming to increase attention resources for subsequent stimuli. To that end, we tested 11 participants in a dual sensory modality task, wherein emotionally negative pictures were contrasted with emotionally neutral pictures and each picture was followed 600 ms later by a tone in an auditory oddball paradigm. Each trial began with a picture displayed for 200 ms; half of the trials began with an emotionally negative picture and half of the trials began with an emotionally neutral picture; 600 ms following picture presentation, the participants heard either an oddball tone or a standard tone. At the end of each trial (picture followed by tone), the participants categorized, with a button press, the picture and tone combination. As expected, and consistent with previous studies, we found an enhanced visual late positive potential (latency range=300-700 ms) to the negative picture stimuli. We further found that compared to neutral pictures, negative pictures resulted in early attention and orienting effects to subsequent tones (measured through an enhanced N1 and N2) and sustained attention effects only to the subsequent oddball tones (measured through late processing negativity, latency range=400-700 ms). Number pad responses to both the picture and tone category showed the shortest response latencies and greatest percentage of correct picture-tone categorization on the negative picture followed by oddball tone trials. Consistent with previous work on natural selective attention, our results support the idea that emotional stimuli can alter attention resource allocation. This finding has broad implications for human attention and performance as it specifically shows the conditions in which an emotionally negative stimulus can result in extended stimulus evaluation. Copyright © 2011

  13. Using Thermal Radiation in Detection of Negative Obstacles

    Science.gov (United States)

    Rankin, Arturo L.; Matthies, Larry H.

    2009-01-01

    A method of automated detection of negative obstacles (potholes, ditches, and the like) ahead of ground vehicles at night involves processing of imagery from thermal-infrared cameras aimed at the terrain ahead of the vehicles. The method is being developed as part of an overall obstacle-avoidance scheme for autonomous and semi-autonomous offroad robotic vehicles. The method could also be applied to help human drivers of cars and trucks avoid negative obstacles -- a development that may entail only modest additional cost inasmuch as some commercially available passenger cars are already equipped with infrared cameras as aids for nighttime operation.

  14. Negative ion sources for tandem accelerator

    International Nuclear Information System (INIS)

    Minehara, Eisuke

    1980-08-01

    Four kinds of negative ion sources (direct extraction Duoplasmatron ion source, radial extraction Penniing ion source, lithium charge exchange ion source and Middleton-type sputter ion source) have been installed in the JAERI tandem accelerator. The ion sources can generate many negative ions ranging from Hydrogen to Uranium with the exception of Ne, Ar, Kr, Xe and Rn. Discussions presented in this report include mechanisms of negative ion formation, electron affinity and stability of negative ions, performance of the ion sources and materials used for negative ion production. Finally, the author will discuss difficult problems to be overcome in order to get any negative ion sufficiently. (author)

  15. 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...

  16. 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 h...

  17. Negative concord and the scope of universals

    NARCIS (Netherlands)

    Giannakidou, A

    2000-01-01

    In this paper, I propose an analysis of Greek negative concord (NC) in terms of quantifier scope. It is shown that there is no evidence that Greek NC n-words are indefinites or negative quantifiers, NC n-words are analysed as universal quantifiers, which are sensitive to negative polarity, and which

  18. Negative Ions in low pressure discharges

    NARCIS (Netherlands)

    Stoffels - Adamowicz, E.; Stoffels, W.W.; Vender, D.; Haverlag, M.; Kroesen, G.M.W.; Hoog, de F.J.

    1995-01-01

    Several aspects of negative ions in low pressure discharges are treated. The elementary processes, in which negative ions are produced and destroyed, are summarized. The influence of negative ions on plasma operation is analyzed in terms of transport equations. It is shown that diffusion, electric

  19. 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.

  20. 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.

  1. Molecular basis of the triple negative breast cancer

    Directory of Open Access Journals (Sweden)

    Ayse Feyda Nursal

    2015-06-01

    Full Text Available Breast cancer is the most common type of cancer in women and more than 1 million breast cancer cases are diagnosed each year all over the world. Breast cancer is a complex and heterogeneous disease in terms of its molecular structure, mutation type, metastase properties, clinical course and therapeutic response. Breast cancer is divided into subtypes based on expression properties of molecular markers as estrogen receptor, progestron receptor, human epidermal growth factor receptor 2. Triple-negative breast cancer is characterized by the lack of tumors that estrogen receptor, progestron receptor, human epidermal growth factor receptor 2 gene expression. These type of tumors lead to agressive clinical course due to unresponsiveness to systemic endocrine therapy and poor prognosis. Triple negative breast cancer constitutes 10-20% of all breast cancers. It affects generally young and African-American women. Triple negative breast cancer have several subtypes based on the gene expression properties. The majority of them are basal-like breast cancers. In this review, current literature is revised and summarized with respect to the molecular basis of triple negative cancers. [Archives Medical Review Journal 2015; 24(2.000: 251-259

  2. Impact of negation salience and cognitive resources on negation during attitude formation.

    Science.gov (United States)

    Boucher, Kathryn L; Rydell, Robert J

    2012-10-01

    Because of the increased cognitive resources required to process negations, past research has shown that explicit attitude measures are more sensitive to negations than implicit attitude measures. The current work demonstrated that the differential impact of negations on implicit and explicit attitude measures was moderated by (a) the extent to which the negation was made salient and (b) the amount of cognitive resources available during attitude formation. When negations were less visually salient, explicit but not implicit attitude measures reflected the intended valence of the negations. When negations were more visually salient, both explicit and implicit attitude measures reflected the intended valence of the negations, but only when perceivers had ample cognitive resources during encoding. Competing models of negation processing, schema-plus-tag and fusion, were examined to determine how negation salience impacts the processing of negations.

  3. 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

  4. NegGOA: negative GO annotations selection using ontology structure.

    Science.gov (United States)

    Fu, Guangyuan; Wang, Jun; Yang, Bo; Yu, Guoxian

    2016-10-01

    Predicting the biological functions of proteins is one of the key challenges in the post-genomic era. Computational models have demonstrated the utility of applying machine learning methods to predict protein function. Most prediction methods explicitly require a set of negative examples-proteins that are known not carrying out a particular function. However, Gene Ontology (GO) almost always only provides the knowledge that proteins carry out a particular function, and functional annotations of proteins are incomplete. GO structurally organizes more than tens of thousands GO terms and a protein is annotated with several (or dozens) of these terms. For these reasons, the negative examples of a protein can greatly help distinguishing true positive examples of the protein from such a large candidate GO space. In this paper, we present a novel approach (called NegGOA) to select negative examples. Specifically, NegGOA takes advantage of the ontology structure, available annotations and potentiality of additional annotations of a protein to choose negative examples of the protein. We compare NegGOA with other negative examples selection algorithms and find that NegGOA produces much fewer false negatives than them. We incorporate the selected negative examples into an efficient function prediction model to predict the functions of proteins in Yeast, Human, Mouse and Fly. NegGOA also demonstrates improved accuracy than these comparing algorithms across various evaluation metrics. In addition, NegGOA is less suffered from incomplete annotations of proteins than these comparing methods. The Matlab and R codes are available at https://sites.google.com/site/guoxian85/neggoa gxyu@swu.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. 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.

  6. 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)

    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

    2017-01-01

    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. PMID:28831437

  7. 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.

  8. Electrochemical cell and negative electrode therefor

    Science.gov (United States)

    Kaun, Thomas D.

    1982-01-01

    A secondary electrochemical cell with the positive and negative electrodes separated by a molten salt electrolyte with the negative electrode comprising a particulate mixture of lithium-aluminum alloy and electrolyte and an additive selected from graphitized carbon, Raney iron or mixtures thereof. The lithium-aluminum alloy is present in the range of from about 45 to about 80 percent by volume of the negative electrode, and the electrolyte is present in an amount not less than about 10 percent by volume of the negative electrode. The additive of graphitized carbon is present in the range of from about 1 to about 10 percent by volume of the negative electrode, and the Raney iron additive is present in the range of from about 3 to about 10 percent by volume of the negative electrode.

  9. On multiphase negative flash for ideal solutions

    DEFF Research Database (Denmark)

    Yan, Wei; Stenby, Erling Halfdan

    2012-01-01

    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......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...

  10. 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.

  11. 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.

  12. Stop Negative Thinking Effects for Drug Dependence

    OpenAIRE

    Windiarti, Sri Endang; Indriati, Indriati; Surachmi, Fajar

    2013-01-01

    The purpose of this study was to determine the effect of therapy stop thinking negatively against drug addiction in Rehabilitation Orphanage Rumah Damai Gunung Pati Semarang. This research is quasy experiment with pretest - posttes without the control group design. Thirty respondents were taken to the reseach sujects. Stop thinking negative therapy before and after thebehavior of drug addiction there are differences (t = 0.00), so it can be stated that the therapy stop thinking negatively inf...

  13. 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.

  14. 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.

  15. Detection of negative energy: 4-dimensional examples

    International Nuclear Information System (INIS)

    Davies, P.C.W.; Ottewill, Adrian C.

    2002-01-01

    We study the response of switched particle detectors to static negative energy densities and negative energy fluxes. It is demonstrated how the switching leads to excitation even in the vacuum and how negative energy can lead to a suppression of this excitation. We obtain quantum inequalities on the detection similar to those obtained for the energy density by Ford and co-workers and in an 'operational' context by Helfer. We reexamine the question 'Is there a quantum equivalence principle?' in terms of our model. Finally, we briefly address the issue of negative energy and the second law of thermodynamics

  16. Physics of negative refractive index materials

    International Nuclear Information System (INIS)

    Ramakrishna, S Anantha

    2005-01-01

    In the past few years, new developments in structured electromagnetic materials have given rise to negative refractive index materials which have both negative dielectric permittivity and negative magnetic permeability in some frequency ranges. The idea of a negative refractive index opens up new conceptual frontiers in photonics. One much-debated example is the concept of a perfect lens that enables imaging with sub-wavelength image resolution. Here we review the fundamental concepts and ideas of negative refractive index materials. First we present the ideas of structured materials or meta-materials that enable the design of new materials with a negative dielectric permittivity, negative magnetic permeability and negative refractive index. We discuss how a variety of resonance phenomena can be utilized to obtain these materials in various frequency ranges over the electromagnetic spectrum. The choice of the wave-vector in negative refractive index materials and the issues of dispersion, causality and energy transport are analysed. Various issues of wave propagation including nonlinear effects and surface modes in negative refractive materials (NRMs) are discussed. In the latter part of the review, we discuss the concept of a perfect lens consisting of a slab of a NRM. This perfect lens can image the far-field radiative components as well as the near-field evanescent components, and is not subject to the traditional diffraction limit. Different aspects of this lens such as the surface modes acting as the mechanism for the imaging of the evanescent waves, the limitations imposed by dissipation and dispersion in the negative refractive media, the generalization of this lens to optically complementary media and the possibility of magnification of the near-field images are discussed. Recent experimental developments verifying these ideas are briefly covered

  17. Cesium injection system for negative ion duoplasmatrons

    International Nuclear Information System (INIS)

    Kobayashi, M.; Prelec, K.; Sluyters, T.J.

    1978-01-01

    A design for admitting cesium vapor into a hollow hydrogen plasma discharge in a duoplasmatron ion source for the purpose of increasing the negative hydrogen ion output current is described. 60 mA beam currents for negative hydrogen ions are reported

  18. Finite Metric Spaces of Strictly Negative Type

    DEFF Research Database (Denmark)

    Hjorth, Poul; Lisonek, P.; Markvorsen, Steen

    1998-01-01

    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...

  19. 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...

  20. Stochastic background of negative binomial distribution

    International Nuclear Information System (INIS)

    Suzuki, N.; Biyajima, M.; Wilk, G.

    1991-01-01

    A branching equations of the birth process with immigration is taken as a model for the particle production process. Using it we investigate cases in which its solution becomes the negative binomial distribution. Furthermore, we compare our approach with the modified negative binomial distribution proposed recently by Chliapnikov and Tchikilev and use it to analyse the observed multiplicity distributions. (orig.)

  1. Atomic capture of negative mesons in hydrogen

    International Nuclear Information System (INIS)

    Leon, M.

    1979-01-01

    After a brief description of the present state of theoretical understanding of atomic capture of negative mesons, a very simple model calculation of negative muon capture by the simplest atoms, hydrogen is described. Also the possibility of generalizing these results to more complicated atoms and even molecules is noted. 15 references

  2. Bootstrapping Visual Categorization with Relevant Negatives

    NARCIS (Netherlands)

    Li, X.; Snoek, C.G.M.; Worring, M.; Koelma, D.; Smeulders, A.W.M.

    Learning classifiers for many visual concepts are important for image categorization and retrieval. As a classifier tends to misclassify negative examples which are visually similar to positive ones, inclusion of such misclassified and thus relevant negatives should be stressed during learning.

  3. Social negative bootstrapping for visual categorization

    NARCIS (Netherlands)

    Li, X.; Snoek, C.G.M.; Worring, M.; Smeulders, A.W.M.

    2011-01-01

    To learn classifiers for many visual categories, obtaining labeled training examples in an efficient way is crucial. Since a classifier tends to misclassify negative examples which are visually similar to positive examples, inclusion of such informative negatives should be stressed in the learning

  4. 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

  5. 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…

  6. Distress attributed to negative symptoms in schizophrenia

    NARCIS (Netherlands)

    Selten, JP; Wiersma, D; van den Bosch, RJ

    2000-01-01

    The purpose of the study was to examine (1) to which negative symptoms schizophrenia patients attribute distress and (2) whether clinical variables can predict the levels of reported distress. With the help of a research assistant, 86 hospitalized patients completed a self-rating scale for negative

  7. Brilliant but Cruel: Perceptions of Negative Evaluators.

    Science.gov (United States)

    Amabile, Teresa M.

    Two studies examined the hypothesis that negative evaluators will be perceived as more intelligent than positive evalutors. Two types of stimuli were used: excerpts from actual negative and positive book reviews, and versions of those excerpts that were edited so that the balance of the reviews varied but the content did not. The results strongly…

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

    African Journals Online (AJOL)

    Post-operative complications were noted in 3% of the negative appendicectomy group but in the positive appendicectomy group complications were much more common particularly when the appendix was ruptured. (Key Words: Negative appendicectomy, perforated appendix and postoperative complications.) Sahel Med.

  9. Negative incidental emotions augment fairness sensitivity.

    Science.gov (United States)

    Liu, Cuizhen; Chai, Jing Wen; Yu, Rongjun

    2016-04-22

    Previous studies have shown that task-unrelated emotions induced incidentally exert carryover effects on individuals' subsequent decisions in financial negotiations. However, the specificity of these emotion effects are not clear. In three experiments, we systematically investigated the role of seven transiently induced basic emotions (disgust, sadness, anger, fear, happiness, surprise and neutral) on rejection of unfair offers using the ultimatum game. We found that all negative emotions (disgust, sadness, anger and fear), but not happiness or surprise, significantly increased rejection rates, suggesting that the effect of incidental negative emotions on fairness is not specific to the type of negative emotion. Our findings highlight the role of fleeting emotions in biasing decision-making processes and suggest that all incidental negative emotions exert similar effects on fairness sensitivity, possibly by potentiating attention towards negative aspects of the situation.

  10. Suggestibility and negative priming: two replication studies.

    Science.gov (United States)

    David, Daniel; Brown, Richard J

    2002-07-01

    Research suggests that inhibiting the effect of irrelevant stimuli on subsequent thought and action (cognitive inhibition) may be an important component of suggestibility. Two small correlation studies were conducted to address the relationship between different aspects of suggestibility and individual differences in cognitive inhibition, operationalized as the degree of negative priming generated by to-be-ignored stimuli in a semantic categorization task. The first study found significant positive correlations between negative priming, hypnotic suggestibility, and creative imagination; a significant negative correlation was obtained between negative priming and interrogative suggestibility, demonstrating the discriminant validity of the study results. The second study replicated the correlation between negative priming and hypnotic suggestibility, using a different suggestibility measurement procedure that assessed subjective experience and hypnotic involuntariness as well as objective responses to suggestions. These studies support the notion that the ability to engage in cognitive inhibition may be an important component of hypnotic responsivity and maybe of other forms of suggestibility.

  11. Surface negative ion production in ion sources

    International Nuclear Information System (INIS)

    Belchenko, Y.

    1993-01-01

    Negative ion sources and the mechanisms for negative ion production are reviewed. Several classes of sources with surface origin of negative ions are examined in detail: surface-plasma sources where ion production occurs on the electrode in contact with the plasma, and ''pure surface'' sources where ion production occurs due to conversion or desorption processes. Negative ion production by backscattering, impact desorption, and electron- and photo-stimulated desorption are discussed. The experimental efficiencies of intense surface negative ion production realized on electrodes contacted with hydrogen-cesium or pure hydrogen gas-discharge plasma are compared. Recent modifications of surface-plasma sources developed for accelerator and fusion applications are reviewed in detail

  12. Negative permeability from random particle composites

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, Shahid, E-mail: shussain2@qinetiq.com

    2017-04-15

    Artificial media, such as those composed of periodically-spaced wires for negative permittivity and split ring resonators for negative permeability have been extensively investigated for negative refractive index (NRI) applications (Smith et al., 2004; Pendry et al., 1999) [1,2]. This paper presents an alternative method for producing negative permeability: granular (or particulate) composites incorporating magnetic fillers. Artificial media, such as split-ring resonators, are designed to produce a magnetic resonance feature, which results in negative permeability over a narrow frequency range about the resonance frequency. The position of the feature is dependent upon the size of the inclusion. The material in this case is anisotropic, such that the feature is only observable when the materials are orientated in a specific direction relative to the applied field. A similar resonance can be generated in magnetic granular (particulate) materials: ferromagnetic resonance from the natural spin resonance of particles. Although the theoretical resonance profiles in granular composites shows the permeability dipping to negative values, this is rarely observed experimentally due to resonance damping effects. Results are presented for iron in spherical form and in flake form, dispersed in insulating host matrices. The two particle shapes show different permeability performance, with the magnetic flakes producing a negative contribution. This is attributed to the stronger coupling with the magnetic field resulting from the high aspect ratio of the flakes. The accompanying ferromagnetic resonance is strong enough to overcome the effects of damping and produce negative permeability. The size of random particle composites is not dictated by the wavelength of the applied field, so the materials are potentially much thinner than other, more traditional artificial composites at microwave frequencies. - Highlights: • Negative permeability from random particle composites is

  13. 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

  14. Ice nucleation triggered by negative pressure.

    Science.gov (United States)

    Marcolli, Claudia

    2017-11-30

    Homogeneous ice nucleation needs supercooling of more than 35 K to become effective. When pressure is applied to water, the melting and the freezing points both decrease. Conversely, melting and freezing temperatures increase under negative pressure, i.e. when water is stretched. This study presents an extrapolation of homogeneous ice nucleation temperatures from positive to negative pressures as a basis for further exploration of ice nucleation under negative pressure. It predicts that increasing negative pressure at temperatures below about 262 K eventually results in homogeneous ice nucleation while at warmer temperature homogeneous cavitation, i. e. bubble nucleation, dominates. Negative pressure occurs locally and briefly when water is stretched due to mechanical shock, sonic waves, or fragmentation. The occurrence of such transient negative pressure should suffice to trigger homogeneous ice nucleation at large supercooling in the absence of ice-nucleating surfaces. In addition, negative pressure can act together with ice-inducing surfaces to enhance their intrinsic ice nucleation efficiency. Dynamic ice nucleation can be used to improve properties and uniformity of frozen products by applying ultrasonic fields and might also be relevant for the freezing of large drops in rainclouds.

  15. 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.

  16. Distinguishing Entailment and Presupposition Under Negation Test

    Directory of Open Access Journals (Sweden)

    Gatri Asti Putri Indarti

    2016-12-01

    Full Text Available Distinguishing entailment from presupposition is quite difficult because their semantic relation seems to be similar. Both entailment and presupposition have an automatic relationship based on the context. However, those semantic relations can still be differentiated by using negation test to show whether a pair is entailment or presupposition. This research focuses on sentences and utterances. Thus, this research aims to analyze and test pairs of entailment and pairs of presupposition by using negation in utterances. The data were twelve comic strips from the Internet and they were analysed by using a negation test. The analysis shows that negation test is useful to test entailment and presupposition in the comic strips. It can be concluded that the difficulty of distinguishing pair of entailment and presupposition in the comic strip using negation test has been successfully solved. In this case, negation test is suitable to test entailment and presupposition. This research can be developed further by other researchers to distinguish entailment and presupposition by using another test if the negation test cannot be used to any further extent.   DOI: https://doi.org/10.24071/llt.2015.180104

  17. Lateralization of cortical negative motor areas.

    Science.gov (United States)

    Borggraefe, Ingo; Catarino, Claudia B; Rémi, Jan; Vollmar, Christian; Peraud, Aurelia; Winkler, Peter A; Noachtar, Soheyl

    2016-10-01

    The lateral and mesial aspects of the central and frontal cortex were studied by direct electrical stimulation of the cortex in epilepsy surgery candidates in order to determine the localization of unilateral and bilateral negative motor responses. Results of electrical cortical stimulation were examined in epilepsy surgery candidates in whom invasive electrodes were implanted. The exact localization of subdural electrodes was defined by fusion of 3-dimensional reconstructed MRI and CT images in 13 patients and by analysis of plane skull X-rays and intraoperative visual localization of the electrodes in another 7 patients. Results of electrical stimulation of the cortex were evaluated in a total of 128 patients in whom invasive electrodes were implanted for planning resective epilepsy surgery. Twenty patients, in whom negative motor responses were obtained, were included in the study. Bilateral upper limb negative motor responses were more often elicited from stimulation of the mesial frontal cortex whereas stimulation of the lateral central cortex leads to contralateral upper limb negative motor responses (pfrontal gyrus whereas contralateral negative motor responses localized predominantly in the anterior part of the precentral gyrus (pgyrus and the mesial fronto-central cortex showing functional differences with regard to unilateral and bilateral upper limb representation. The lateral fronto-central negative motor area serves predominantly contralateral upper limb motor control whereas the mesial frontal negative motor area represents bilateral upper limb movement control. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  18. A controlled trial of automated classification of negation from clinical notes

    Directory of Open Access Journals (Sweden)

    Carruth William

    2005-05-01

    Full Text Available Abstract Background Identification of negation in electronic health records is essential if we are to understand the computable meaning of the records: Our objective is to compare the accuracy of an automated mechanism for assignment of Negation to clinical concepts within a compositional expression with Human Assigned Negation. Also to perform a failure analysis to identify the causes of poorly identified negation (i.e. Missed Conceptual Representation, Inaccurate Conceptual Representation, Missed Negation, Inaccurate identification of Negation. Methods 41 Clinical Documents (Medical Evaluations; sometimes outside of Mayo these are referred to as History and Physical Examinations were parsed using the Mayo Vocabulary Server Parsing Engine. SNOMED-CT™ was used to provide concept coverage for the clinical concepts in the record. These records resulted in identification of Concepts and textual clues to Negation. These records were reviewed by an independent medical terminologist, and the results were tallied in a spreadsheet. Where questions on the review arose Internal Medicine Faculty were employed to make a final determination. Results SNOMED-CT was used to provide concept coverage of the 14,792 Concepts in 41 Health Records from John's Hopkins University. Of these, 1,823 Concepts were identified as negative by Human review. The sensitivity (Recall of the assignment of negation was 97.2% (p Conclusion Automated assignment of negation to concepts identified in health records based on review of the text is feasible and practical. Lexical assignment of negation is a good test of true Negativity as judged by the high sensitivity, specificity and positive likelihood ratio of the test. SNOMED-CT had overall coverage of 88.7% of the concepts being negated.

  19. Kaposi’s sarcoma in an HIV-negative patient

    Directory of Open Access Journals (Sweden)

    Clara Georgina Garcia Lahera

    2015-06-01

    Full Text Available Kaposi’s sarcoma is a vascular tumour of the skin, most frequently seen in men over 50 years of age, of long-term progress and low mortality. It is related to the infection caused by the human immunodeficiency virus (HIV; it appears in the advanced stages of the disease and with immunosuppression, affecting approximately 20 % of the people with HIV who do not take antiretroviral drugs. This is a case of an urban female patient who did not have a history of disease and who began to have squamous erythematous lesions on the right foot and on the thighs. A skin biopsy was performed and the patient was diagnosed with a Kaposi’s sarcoma. The patient was HIV-negative. This case is presented as it is a rare condition in an HIV-negative patient.

  20. Negative regulators of brown adipose tissue (BAT)-mediated thermogenesis.

    Science.gov (United States)

    Sharma, Bal Krishan; Patil, Mallikarjun; Satyanarayana, Ande

    2014-12-01

    Brown adipose tissue (BAT) is specialized for energy expenditure, a process called adaptive thermogenesis. PET-CT scans recently demonstrated the existence of metabolically active BAT in adult humans, which revitalized our interest in BAT. Increasing the amount and/or activity of BAT holds tremendous promise for the treatment of obesity and its associated diseases. PGC1α is the master regulator of UCP1-mediated thermogenesis in BAT. A number of proteins have been identified to influence thermogenesis either positively or negatively through regulating the expression or transcriptional activity of PGC1α. Therefore, BAT activation can be achieved by either inducing the expression of positive regulators of PGC1α or by inhibiting the repressors of the PGC1α/UCP1 pathway. Here, we review the most important negative regulators of PGC1α/UCP1 signaling and their mechanism of action in BAT-mediated thermogenesis. © 2014 Wiley Periodicals, Inc.

  1. Negative-strand RNA viruses: the plant-infecting counterparts.

    Science.gov (United States)

    Kormelink, Richard; Garcia, Maria Laura; Goodin, Michael; Sasaya, Takahide; Haenni, Anne-Lise

    2011-12-01

    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 organization, while others have just recently been/or are still classified in floating genera. In most cases, at least two striking differences can still be discerned between the animal/human-infecting viruses and their plant-infecting counterparts which for the latter relate to their adaptation to plants as hosts. The first one is the capacity to modify plasmodesmata to facilitate systemic spread of infectious viral entities throughout the plant host. The second one is the capacity to counteract RNA interference (RNAi, also referred to as RNA silencing), the innate antiviral defence system of plants and insects. In this review an overview will be presented on the negative-strand RNA plant viruses classified within the families Bunyaviridae, Rhabdoviridae, Ophioviridae and floating genera Tenuivirus and Varicosavirus. Genetic differences with the animal-infecting counterparts and their evolutionary descendants will be described in light of the above processes. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. 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.

  3. 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....

  4. How does negative emotion cause false memories?

    Science.gov (United States)

    Brainerd, C J; Stein, L M; Silveira, R A; Rohenkohl, G; Reyna, V F

    2008-09-01

    Remembering negative events can stimulate high levels of false memory, relative to remembering neutral events. In experiments in which the emotional valence of encoded materials was manipulated with their arousal levels controlled, valence produced a continuum of memory falsification. Falsification was highest for negative materials, intermediate for neutral materials, and lowest for positive materials. Conjoint-recognition analysis produced a simple process-level explanation: As one progresses from positive to neutral to negative valence, false memory increases because (a) the perceived meaning resemblance between false and true items increases and (b) subjects are less able to use verbatim memories of true items to suppress errors.

  5. Double Negative Materials (DNM), Phenomena and Applications

    Science.gov (United States)

    2009-07-01

    5697–5711. Maksimović, M., and Z. Jakšić. “Emittance and Absorptance Tailoring by Negative Refractive Index Metamaterial-Based Cantor Multilayers.” J...TOKEN=48950826 Popov, A. K., S. A. Myslivets, T. F. George , and V. M. Shalaev. “Tailoring Transparency of Negative-Index Metamaterials With Parametric...Popov, A. K., S. A. Myslivets, T. F. George , and V. M. Shalaev. “Compensating Losses in Positive- and Negative-Index Metamaterials Through

  6. The brief negative symptom scale: psychometric properties.

    Science.gov (United States)

    Kirkpatrick, Brian; Strauss, Gregory P; Nguyen, Linh; Fischer, Bernard A; Daniel, David G; Cienfuegos, Angel; Marder, Stephen R

    2011-03-01

    The participants in the NIMH-MATRICS Consensus Development Conference on Negative Symptoms recommended that an instrument be developed that measured blunted affect, alogia, asociality, anhedonia, and avolition. The Brief Negative Symptom Scale (BNSS) is a 13-item instrument designed for clinical trials and other studies that measures these 5 domains. The interrater, test-retest, and internal consistency of the instrument were strong, with respective intraclass correlation coefficients of 0.93 for the BNSS total score and values of 0.89-0.95 for individual subscales. Comparisons with positive symptoms and other negative symptom instruments supported the discriminant and concurrent validity of the instrument.

  7. Negative dimensions in quantum field theory

    International Nuclear Information System (INIS)

    Ricotta, R.M.

    1989-01-01

    The basic fundaments of the negative dimensional integration method are reviewed. Its properties and the calculations of few Feynman amplitudes are presented as well as other new applications of the method. (author)

  8. Exploring the Psychological Influence of Perceived Negative ...

    African Journals Online (AJOL)

    Nneka Umera-Okeke

    2017-10-14

    Oct 14, 2017 ... This paper critically examined the psychological influence of ... development, there are some perceived negative foreign factors that have constituted ..... essence, it is the sum total of the individual's cognitive, intellectual and ...

  9. Nonlinear waves in plasma with negative ion

    International Nuclear Information System (INIS)

    Saito, Maki; Watanabe, Shinsuke; Tanaca, Hiroshi.

    1984-01-01

    The propagation of nonlinear ion wave is investigated theoretically in a plasma with electron, positive ion and negative ion. The ion wave of long wavelength is described by a modified K-dV equation instead of a K-dV equation when the nonlinear coefficient of the K-dV equation vanishes at the critical density of negative ion. In the vicinity of the critical density, the ion wave is described by a coupled K-dV and modified K-dV equation. The transition from a compressional soliton to a rarefactive soliton and vice versa are examined by the coupled equation as a function of the negative ion density. The ion wave of short wavelength is described by a nonlinear Schroedinger equation. In the plasma with a negative ion, the nonlinear coefficient of the nonlinear Schroedinger equation changes the sign and the ion wave becomes modulationally unstable. (author)

  10. The strategic significance of negative externalities.

    Science.gov (United States)

    2012-12-01

    Negative externalities have competitive relevance in a market when they have selective impacts as, for : example, when a product in use imposes greater costs on consumers of rival products than on other people. : Because managers have discretion ...

  11. Negative ion formation processes: A general review

    International Nuclear Information System (INIS)

    Alton, G.D.

    1990-01-01

    The principal negative ion formation processes will be briefly reviewed. Primary emphasis will be placed on the more efficient and universal processes of charge transfer and secondary ion formation through non-thermodynamic surface ionization. 86 refs., 20 figs

  12. Unrevealing culture-negative severe sepsis

    OpenAIRE

    de Prost, Nicolas; Razazi, Keyvan; Brun-Buisson, Christian

    2013-01-01

    Sepsis involves a wide array of sources and microorganisms, only a fraction of which are microbiologically documented. Culture-negative sepsis poses special diagnostic challenges to both clinicians and microbiologists and further questions the validity of sepsis definitions.

  13. Contingent negative variation of mood disorder patients

    Institute of Scientific and Technical Information of China (English)

    Yingzhi Lu; Wenbin Zong; Qingtao Ren; Jinyu Pu; Jun Chen; Juan Li; Xingshi Chen; Yong Wang

    2011-01-01

    Studies on brain-evoked potential and contingent negative variation (CNV) in mood disorder remain controversial. To date, no CNV difference between unipolar and bipolar depression has been reported. Brain-evoked potentials were measured in the present study to analyze CNV in three subtypes of mood disorder (mania, unipolar depression, and bipolar depression), and these results were compared with normal controls. In the mania group, CNV amplitude B was greater than in controls, and the depression group exhibited lower CNV amplitude B and smaller A-S'2 area, and prolonged post-imperative negative variation latency. The CNV comparison between unipolar and bipolar depression found that the prolonged post-imperative negative variation latency was only in unipolar depression. These results suggest that prolonged post-imperative negative variation latency is a characteristic of unipolar depression, and CNV amplitude change is a state characteristic of mood disorder patients.

  14. Dispersion characteristics of negative refraction sonic crystals

    International Nuclear Information System (INIS)

    Wu, L.-Y.; Chen, L.-W.; Wang, R.C.-C.

    2008-01-01

    Dispersion characteristics of negative refraction sonic crystals are investigated. The plane wave expansion method is used to calculate the equifrequency surface; the dependences of refractive direction on frequencies and incident angles for triangular lattices are shown. There exist the positive and negative refractive waves which include k.V g ≥0 and k.V g ≤0 in the second band for the triangular system. We also use the finite element method to demonstrate that the relative intensity of the transmitted acoustic waves is dependent on incident frequencies and angles. The positions of the partial band gaps obtained by the plane wave expansion method are in good agreement with those obtained by the finite element method. The sonic crystals with negative effective index are shown to have higher transmission intensities. By using the negative refraction behavior, we can design a sonic crystal plane lens to focus a sonic wave

  15. Negative muon capture in noble gas mixtures

    International Nuclear Information System (INIS)

    Hutson, R.L.; Knight, J.D.; Leon, M.; Schillaci, M.E.; Knowles, H.B.; Reidy, J.J.

    1980-01-01

    We have determined the probabilities of atomic negative muon capture in binary mixtures of the gases He, Ne, Ar, and Kr at partial pressures near five atmospheres. Relative capture rates were deduced from measured muonic X-ray yields. (orig.)

  16. On negative norm states in supersymmetric theories

    International Nuclear Information System (INIS)

    Ellwanger, U.

    1983-01-01

    We study the effective kinetic energy of scalar fields for two classes of supersymmetric theories. In theories with very large VEVs of scalar fields, as proposed by Witten, the use of the renormalization group improved effective action prevents the appearance of negative norm states. For simpler theories a general criterium for the absence of negative norm states is given, which is violated in a model with O(N)-symmetry proposed recently. (orig.)

  17. Consumer's Negative emotions, Financial Decisions, Financial Advice

    OpenAIRE

    Konstantaki, Violetta

    2007-01-01

    Abstract The purpose of this study is to explore the consumers decision making process. In particular, this study attempts to examine consumers negative emotions, which elicit during a decision processing. Especially, the case of a financial decision will be examined. Moreover, consumers negative emotion will be investigated in relation with consumers coping behaviour. To be more specific, the option of seeking advice as a successful consumers coping behaviour will be explor...

  18. Negative reciprocity and retrenched pension rights

    OpenAIRE

    Montizaan, R.M.; Cörvers, F.; de Grip, A.; Dohmen, T.J.

    2012-01-01

    We document the importance of negatively reciprocal inclinations in labor relationships by showing that a retrenchment of pension rights, which is perceived as unfair, causes a larger reduction in job motivation the stronger workers' negatively reciprocal inclinations are. We exploit unique matched survey and administrative data on male employees in the public sector in the Netherlands and compare the job motivation of employees born in 1950, who faced a substantial retrenchment of their pens...

  19. Superconductive microstrip exhibiting negative differential resistivity

    International Nuclear Information System (INIS)

    Huebener, R.P.; Gallus, D.E.

    1975-01-01

    A device capable of exhibiting negative differential electrical resistivity over a range of values of current and voltage is formed by vapor-depositing a thin layer of a material capable of exhibiting superconductivity on an insulating substrate, establishing electrical connections at opposite ends of the deposited strip, and cooling the alloy into its superconducting range. The device will exhibit negative differential resistivity when biased in the current-induced resistive state

  20. Negative ion sound solitary waves revisited

    Science.gov (United States)

    Cairns, R. A.; Cairns

    2013-12-01

    Some years ago, a group including the present author and Padma Shukla showed that a suitable non-thermal electron distribution allows the formation of ion sound solitary waves with either positive or negative density perturbations, whereas with Maxwellian electrons only a positive density perturbation is possible. The present paper discusses the qualitative features of this distribution allowing the negative waves and shared with suitable two-temperature distributions.

  1. 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.

  2. The Brief Negative Symptom Scale: Psychometric Properties

    OpenAIRE

    Kirkpatrick, Brian; Strauss, Gregory P.; Nguyen, Linh; Fischer, Bernard A.; Daniel, David G.; Cienfuegos, Angel; Marder, Stephen R.

    2010-01-01

    The participants in the NIMH-MATRICS Consensus Development Conference on Negative Symptoms recommended that an instrument be developed that measured blunted affect, alogia, asociality, anhedonia, and avolition. The Brief Negative Symptom Scale (BNSS) is a 13-item instrument designed for clinical trials and other studies that measures these 5 domains. The interrater, test–retest, and internal consistency of the instrument were strong, with respective intraclass correlation coefficients of 0.93...

  3. Negative ion formation and neutralization processes, (1)

    International Nuclear Information System (INIS)

    Sugiura, Toshio

    1982-01-01

    This review has been made preliminary for the purpose of contribute to the plasma heating by ''negative ion based neutral beam injection'' in the magnetic confinement fusion reactor. A compilation includes the survey of the general processes of negative ion formation, the data of the cross section of H - ion formation and the neutralization of H - ion, and some of new processes of H - ion formation. The data of cross section are mainly experimental, but partly include the results of theoretical calculation. (author)

  4. Negative brain scintigrams in brain tumors

    International Nuclear Information System (INIS)

    Dalke, K.G.

    1978-01-01

    With 53 histologically verified and 2 histologically not identified brain tumors, that showed a negative scintigram, it was tried to find reasons for the wrong and negative dropout of these scintigrams. The electroencephalograms and angiograms, that were made simultaneously were taken into consideration with respect to their propositional capability and were compared with the scintigram findings. For the formation of the negative brain scintigrams there could be found no unique cause or causal constellation. The scintigraphic tumor representation is likely based on a complex process. Therefore the reasons for the negativity of the brain scintigrams can be a manifold of causes. An important role plays the vascularisation of the tumor, but not in a sole way. As well the tumor localisation gains some importance; especially in the temporal lobe or in the deeper structures situated tumors can be negative in the scintigram. To hold down the rate of wrong-negative quote in the case of intracranial tumor search, one is advised to continue with an further exposure after 2 to 4 hours besides the usual exposures, unless a sequential scintigraphy was made from the beginning. (orig./MG) [de

  5. The Peculiar Negative Greenhouse Effect Over Antarctica

    Science.gov (United States)

    Sejas, S.; Taylor, P. C.; Cai, M.

    2017-12-01

    Greenhouse gases warm the climate system by reducing the energy loss to space through the greenhouse effect. Thus, a common way to measure the strength of the greenhouse effect is by taking the difference between the surface longwave (LW) emission and the outgoing LW radiation. Based on this definition, a paradoxical negative greenhouse effect is found over the Antarctic Plateau, which suprisingly indicates that greenhouse gases enhance energy loss to space. Using 13 years of NASA satellite observations, we verify the existence of the negative greenhouse effect and find that the magnitude and sign of the greenhouse effect varies seasonally and spectrally. A previous explanation attributes the negative greenhouse effect solely to stratospheric CO2 and warmer than surface stratospheric temperatures. However, we surprisingly find that the negative greenhouse effect is predominantly caused by tropospheric water vapor. A novel principle-based explanation provides the first complete account of the Antarctic Plateau's negative greenhouse effect indicating that it is controlled by the vertical variation of temperature and greenhouse gas absorption strength. Our findings indicate that the strong surface-based temperature inversion and scarcity of free tropospheric water vapor over the Antarctic Plateau cause the negative greenhouse effect. These are climatological features uniquely found in the Antarctic Plateau region, explaining why the greenhouse effect is positive everywhere else.

  6. A model for negative ion extraction and comparison of negative ion optics calculations to experimental results

    International Nuclear Information System (INIS)

    Pamela, J.

    1990-10-01

    Negative ion extraction is described by a model which includes electron diffusion across transverse magnetic fields in the sheath. This model allows a 2-Dimensional approximation of the problem. It is used to introduce electron space charge effects in a 2-D particle trajectory code, designed for negative ion optics calculations. Another physical effect, the stripping of negative ions on neutral gas atoms, has also been included in our model; it is found to play an important role in negative ion optics. The comparison with three sets of experimental data from very different negative ion accelerators, show that our model is able of accurate predictions

  7. 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.

  8. 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

    2018-03-01

    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 (M age  = 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.

  9. [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.

  10. 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.

  11. NEVER forget: negative emotional valence enhances recapitulation.

    Science.gov (United States)

    Bowen, Holly J; Kark, Sarah M; Kensinger, Elizabeth A

    2017-07-10

    A hallmark feature of episodic memory is that of "mental time travel," whereby an individual feels they have returned to a prior moment in time. Cognitive and behavioral neuroscience methods have revealed a neurobiological counterpart: Successful retrieval often is associated with reactivation of a prior brain state. We review the emerging literature on memory reactivation and recapitulation, and we describe evidence for the effects of emotion on these processes. Based on this review, we propose a new model: Negative Emotional Valence Enhances Recapitulation (NEVER). This model diverges from existing models of emotional memory in three key ways. First, it underscores the effects of emotion during retrieval. Second, it stresses the importance of sensory processing to emotional memory. Third, it emphasizes how emotional valence - whether an event is negative or positive - affects the way that information is remembered. The model specifically proposes that, as compared to positive events, negative events both trigger increased encoding of sensory detail and elicit a closer resemblance between the sensory encoding signature and the sensory retrieval signature. The model also proposes that negative valence enhances the reactivation and storage of sensory details over offline periods, leading to a greater divergence between the sensory recapitulation of negative and positive memories over time. Importantly, the model proposes that these valence-based differences occur even when events are equated for arousal, thus rendering an exclusively arousal-based theory of emotional memory insufficient. We conclude by discussing implications of the model and suggesting directions for future research to test the tenets of the model.

  12. GATA3 expression in triple-negative breast cancers.

    Science.gov (United States)

    Byrne, David J; Deb, Siddhartha; Takano, Elena A; Fox, Stephen B

    2017-07-01

    GATA-binding protein 3 (GATA3) is a well-studied transcription factor found to be essential in the development of luminal breast epithelium and has been identified in a variety of tumour types, including breast and urothelial carcinomas, making it a useful immunohistochemistry marker in the diagnosis of both primary and metastatic disease. We investigated GATA3 protein expression in a 106 primary triple-negative breast carcinomas (100 basal-like, six non-basal-like) using Cell Marque mouse monoclonal anti-GATA3 (L50-823). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to quantify mRNA expression in 22 triple-negative breast cancers (TNBCs) (20 primary and two cell lines), four luminal (three primary and one cell line) and five human epidermal growth factor receptor 2 (HER2) (four primary and one cell line) amplified tumours. In 98 TNBCs where IHC was assessable, 47 (48%) had a 1+ or greater staining with 20 (21%) having high GATA3 expression when using a weighted scoring. Our study has demonstrated that GATA3 expression is common in primary triple-negative breast carcinomas. It also suggests that although GATA3 is an oestrogen receptor (ER) regulated gene, it still proves useful in differentiating between primary and metastatic tumours in patients with a history of breast cancer regardless of its molecular subtype. © 2017 John Wiley & Sons Ltd.

  13. Confidence Intervals for Asbestos Fiber Counts: Approximate Negative Binomial Distribution.

    Science.gov (United States)

    Bartley, David; Slaven, James; Harper, Martin

    2017-03-01

    The negative binomial distribution is adopted for analyzing asbestos fiber counts so as to account for both the sampling errors in capturing only a finite number of fibers and the inevitable human variation in identifying and counting sampled fibers. A simple approximation to this distribution is developed for the derivation of quantiles and approximate confidence limits. The success of the approximation depends critically on the use of Stirling's expansion to sufficient order, on exact normalization of the approximating distribution, on reasonable perturbation of quantities from the normal distribution, and on accurately approximating sums by inverse-trapezoidal integration. Accuracy of the approximation developed is checked through simulation and also by comparison to traditional approximate confidence intervals in the specific case that the negative binomial distribution approaches the Poisson distribution. The resulting statistics are shown to relate directly to early research into the accuracy of asbestos sampling and analysis. Uncertainty in estimating mean asbestos fiber concentrations given only a single count is derived. Decision limits (limits of detection) and detection limits are considered for controlling false-positive and false-negative detection assertions and are compared to traditional limits computed assuming normal distributions. Published by Oxford University Press on behalf of the British Occupational Hygiene Society 2017.

  14. Negative Campaigning and the Logic of Retaliation in Multiparty Competition.

    Science.gov (United States)

    Dolezal, Martin; Ennser-Jedenastik, Laurenz; Müller, Wolfgang C

    2016-04-01

    The extant literature has demonstrated that the logic of retaliation is a core feature of negative campaigning. Attacks by one side induce counterattacks by the other. Yet most research on the interactive nature of negative campaigning is limited to two-party competition and provides little theoretical justification for why political actors should respond to attacks with counterattacks. The present paper addresses these research gaps. We argue that the negativity bias in human information processing and the zero-sum nature of elections make retaliation a rational strategy. Importantly, these arguments also imply that retaliation may not be the only plausible response to attacks in multiparty systems. Rather, parties may prefer to react to attacks from one competitor by attacking another. To grasp empirically how being attacked and attacking are related, we conduct a highly disaggregated time series analysis of such instances while controlling for other factors that may influence actor behavior. Our analyses draw on several thousand party press releases issued during three national election campaigns in Austria, a typical European multiparty system. They show that retaliation is an important strategy also in multiparty politics. Yet in such context, parties do not exclusively follow a tit-for-tat approach but rather display more complex patterns of attack behavior.

  15. 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).

  16. Nature of negative microplastic deformation in alloys

    International Nuclear Information System (INIS)

    Palatnik, L.S.; Ivantsov, V.I.; Kagan, Ya.I.; Papirov, I.I.; Fat'yanova, N.B.; AN Ukrainskoj SSR, Kharkov. Fiziko-Tekhnicheskij Inst.)

    1985-01-01

    The paper deals with investigation of microplastic deformation of corrosion resistant aging 40KhNYU alloy and the study of physical nature of negative microdeformation in this alloy under tension. Investigation of microplasticity of 40KhNYU alloy was conducted by the method of mechanostatic hysteresis using resistance strain gauge for measuring stresses and deformations. Microplasticity curves for 40KhNYU alloy were obtained. They represent the result of competition between usual (positive) microdeformation and phase (negative) deformation under tensile effect on the alloy. It was established that the negative microdeformation increment occurs during secondary aging of the phase precipitated from initial supersat urated solid solution (primary decomposition product). This phase decomposes under tension with disperse phase precipitation which promotes decreasing its specific volume and specimen volume as a whole

  17. Negative capacitance in a ferroelectric capacitor.

    Science.gov (United States)

    Khan, Asif Islam; Chatterjee, Korok; Wang, Brian; Drapcho, Steven; You, Long; Serrao, Claudy; Bakaul, Saidur Rahman; Ramesh, Ramamoorthy; Salahuddin, Sayeef

    2015-02-01

    The Boltzmann distribution of electrons poses a fundamental barrier to lowering energy dissipation in conventional electronics, often termed as Boltzmann Tyranny. Negative capacitance in ferroelectric materials, which stems from the stored energy of a phase transition, could provide a solution, but a direct measurement of negative capacitance has so far been elusive. Here, we report the observation of negative capacitance in a thin, epitaxial ferroelectric film. When a voltage pulse is applied, the voltage across the ferroelectric capacitor is found to be decreasing with time--in exactly the opposite direction to which voltage for a regular capacitor should change. Analysis of this 'inductance'-like behaviour from a capacitor presents an unprecedented insight into the intrinsic energy profile of the ferroelectric material and could pave the way for completely new applications.

  18. Entanglement negativity bounds for fermionic Gaussian states

    Science.gov (United States)

    Eisert, Jens; Eisler, Viktor; Zimborás, Zoltán

    2018-04-01

    The entanglement negativity is a versatile measure of entanglement that has numerous applications in quantum information and in condensed matter theory. It can not only efficiently be computed in the Hilbert space dimension, but for noninteracting bosonic systems, one can compute the negativity efficiently in the number of modes. However, such an efficient computation does not carry over to the fermionic realm, the ultimate reason for this being that the partial transpose of a fermionic Gaussian state is no longer Gaussian. To provide a remedy for this state of affairs, in this work, we introduce efficiently computable and rigorous upper and lower bounds to the negativity, making use of techniques of semidefinite programming, building upon the Lagrangian formulation of fermionic linear optics, and exploiting suitable products of Gaussian operators. We discuss examples in quantum many-body theory and hint at applications in the study of topological properties at finite temperature.

  19. Backscattering and negative polarization of agglomerate particles.

    Science.gov (United States)

    Zubko, Evgenij; Shkuratov, Yuriy; Hart, Matthew; Eversole, Jay; Videen, Gorden

    2003-09-01

    We used the discrete dipole approximation to study the backscattering of agglomerate particles consisting of oblong monomers. We varied the aspect ratio of the monomers from approximately 1 (sphere) to 4, while we kept the total particle volume equivalent to that of an x = 10 sphere for m = 1.59 + i0 and 1.50 + i0 and considered two values of agglomerate packing density: rho = 0.25 and rho = 0.1. We found that these particles do not display a prominent brightness opposition effect but do produce significant negative polarization over a range of near-backscattering angles. Increasing the monomers' aspect ratio can make the negative polarization much more prominent. We have noted also that decreasing m and p can reduce the amplitude of the negative polarization for these particles.

  20. 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.

  1. 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.

  2. News Media Framing of Negative Campaigning

    DEFF Research Database (Denmark)

    Pedersen, Rasmus Tue

    2014-01-01

    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.......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...

  3. 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...... by describing essential characteristics of negatives, which must be passed on to the copies, and the required metadata and technical imaging specifications. Next the paper discusses strategies for preservation and makes an analysis with the LIFE2 Costing Model. The paper concludes that the most beneficial...... and cost-effective preservation solution for large format negatives is to keep the preservation copies as digital files. However, it also acknowledges that it is important to revisit such strategies regularly to monitor changes in user expectations, technologies and costs....

  4. 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.

  5. Modeling of Trichel pulses in negative corona

    International Nuclear Information System (INIS)

    Napartovich, A.P.; Akishev, Yu. S.; Deryugin, A.A.; Kochetov, I.V.; Pan'kin, M.V.; Trushkin, N.I.

    1998-01-01

    Results are reported of detailed numerical studies of Trichel pulse formation for dry air in short-gap coronas. Continuity equations for electrons, positive and negative ions, and the Poisson equation averaged over the current cross section were solved numerically with appropriate boundary conditions. The results of numerical simulation make it possible to analyze in detail the trailing edge of the Trichel pulse and the inter-pulse pause determining the period between pulses. In particular, the variations of the total number of negative ions in the corona spacing occurring under typical conditions of a pulsating corona, proved to be quite insignificant. A comparison with experiments demonstrated a reasonable agreement both for the shape of the pulse and for the average characteristics of the negative corona. (J.U.)

  6. 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.

  7. Thunderstorm Charge Structures Producing Negative Gigantic Jets

    Science.gov (United States)

    Boggs, L.; Liu, N.; Riousset, J. A.; Shi, F.; Rassoul, H.

    2016-12-01

    Here we present observational and modeling results that provide insight into thunderstorm charge structures that produce gigantic jet discharges. The observational results include data from four different thunderstorms producing 9 negative gigantic jets from 2010 to 2014. We used radar, very high frequency (VHF) and low frequency (LF) lightning data to analyze the storm characteristics, charge structures, and lightning activity when the gigantic jets emerged from the parent thunderstorms. A detailed investigation of the evolution of one of the charge structures by analyzing the VHF data is also presented. The newly found charge structure obtained from the observations was analyzed with fractal modeling and compared with previous fractal modeling studies [Krehbiel et al., Nat. Geosci., 1, 233-237, 2008; Riousset et al., JGR, 115, A00E10, 2010] of gigantic jet discharges. Our work finds that for normal polarity thunderstorms, gigantic jet charge structures feature a narrow upper positive charge region over a wide middle negative charge region. There also likely exists a `ring' of negative screening charge located around the perimeter of the upper positive charge. This is different from previously thought charge structures of the storms producing gigantic jets, which had a very wide upper positive charge region over a wide middle negative charge region, with a very small negative screening layer covering the cloud top. The newly found charge structure results in leader discharge trees in the fractal simulations that closely match the parent flashes of gigantic jets inside and outside the thundercloud. The previously used charge structures, while vital to the understanding of gigantic jet initiation and the role of charge imbalances inside the cloud, do not produce leader discharge trees that agree with observed gigantic jet discharges.Finally, the newly discovered gigantic jet charge structures are formed near the end of a convective pulse [Meyer et al., JGR, 118

  8. Negative contrast peritoneography in the horse

    International Nuclear Information System (INIS)

    Lloyd, K.C.K.; Kerr, L.Y.; Meagher, D.M.; Baker, T.W.; Kurpershoek, C.J.

    1989-01-01

    A method of negative contrast peritoneography using CO 2 peritoneal insufflation technique was investigated in adult horses. Radiographic visualization of anatomic structures in the dorsal abdomen, including the kidneys, portions of the spleen and liver, dorsal stomach and mesenteric root region, was enhanced. Visualization of ventral abdominal structures was not enhanced. Negative contrast peritoneography allowed reduction in the radiographic technique from 140 kVp and 40 mAs before insufflation to 100 kVp and 5–10 mAs following insufflation. The technique was easily and safely performed with minimal patient discomfort and risk

  9. Negative Ion Sources: Magnetron and Penning

    International Nuclear Information System (INIS)

    Faircloth, D C

    2013-01-01

    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. (author)

  10. Necessity of negativity in quantum theory

    International Nuclear Information System (INIS)

    Ferrie, Christopher; Morris, Ryan; Emerson, Joseph

    2010-01-01

    A unification of the set of quasiprobability representations using the mathematical theory of frames was recently developed for quantum systems with finite-dimensional Hilbert spaces, in which it was proven that such representations require negative probability in either the states or the effects. In this article we extend those results to Hilbert spaces of infinite dimension, for which the celebrated Wigner function is a special case. Hence, this article presents a unified framework for describing the set of possible quasiprobability representations of quantum theory, and a proof that the presence of negativity is a necessary feature of such representations.

  11. 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.

  12. Negative refraction using Raman transitions and chirality

    Energy Technology Data Exchange (ETDEWEB)

    Sikes, D. E.; Yavuz, D. D. [Department of Physics, 1150 University Avenue, University of Wisconsin at Madison, Madison, Wisconsin 53706 (United States)

    2011-11-15

    We present a scheme that achieves negative refraction with low absorption in far-off resonant atomic systems. The scheme utilizes Raman resonances and does not require the simultaneous presence of an electric-dipole transition and a magnetic-dipole transition near the same wavelength. We show that two interfering Raman tran-sitions coupled to a magnetic-dipole transition can achieve a negative index of refraction with low absorption through magnetoelectric cross-coupling. We confirm the validity of the analytical results with exact numerical simulations of the density matrix. We also discuss possible experimental implementations of the scheme in rare-earth metal atomic systems.

  13. Proactive and Retroactive Effects of Negative Suggestion

    Science.gov (United States)

    Brown, Alan S.; Brown, Christine M.; Mosbacher, Joy L.; Dryden, W. Erich

    2006-01-01

    The negative effects of false information presented either prior to (proactive interference; PI) or following (retroactive interference; RI) true information was examined with word definitions (Experiment 1) and trivia facts (Experiment 2). Participants were explicitly aware of which information was true and false when shown, and true-false…

  14. [Negative symptoms in schizophrenia: psychotherapeutic approaches].

    Science.gov (United States)

    Azorin, J-M; Adida, M; Belzeaux, R; Pringuey, D; Micoulaud Franchi, J-A; Simon, N; Cermolacce, M; Kaladjian, A; Fakra, E

    2015-12-01

    Although negative symptoms are recognized as a central feature of schizophrenia, their definition as well as phenomenology have long been a vexing issue. During these last years, a major progress has been made with the delineation of two underlying subdomains of negative symptoms: diminished expression and anhedonia-avolition-apathy. As current guidelines are not always in accord on the efficacy of treatments on negative symptoms, it may be tempting to re-interpret the findings of clinical trials by looking at the effects of treatments on these two subdomains. This could concern both psychotropic treatments and psychotherapeutic interventions. Furthermore, neuroimaging as well as emotional response studies have permitted to better understand the mechanism which could be at the root of diminished expression and anhedonia in schizophrenia. On this basis, new psychotherapeutic methods have been devised which, by specifically targeting these two subdomains, are likely to be more efficient on negative symptoms. Further research is warranted to test their efficacy in randomized controlled trials. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. [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.

  16. Cortical evidence for negative search templates

    NARCIS (Netherlands)

    Reeder, Reshanne R.; Olivers, Christian N.L.; Pollmann, Stefan

    2017-01-01

    A “target template”, specifying target features, is thought to benefit visual search performance. Setting up a “negative template”, specifying distractor features, should improve distractor inhibition and also benefit target detection. In the current fMRI study, subjects were required to search for

  17. Suicidal Fantasies and Positive/Negative Effects.

    Science.gov (United States)

    Fouts, Gregory; Norrie, Janice

    This study attempted to provide some initial normative data to help professionals and researchers to distinguish between playful and stimulating suicidal fantasies as opposed to serious and compulsive thoughts and behaviours characterized by negative affects. It is argued that the former is a natural consequence of cognitive development, the entry…

  18. 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...

  19. Quantum Heat Engine and Negative Boltzmann Temperature

    International Nuclear Information System (INIS)

    Xi Jing-Yi; Quan Hai-Tao

    2017-01-01

    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. (paper)

  20. 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

  1. 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...

  2. 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…

  3. 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...

  4. 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...

  5. Shifted Non-negative Matrix Factorization

    DEFF Research Database (Denmark)

    Mørup, Morten; Madsen, Kristoffer Hougaard; Hansen, Lars Kai

    2007-01-01

    Non-negative matrix factorization (NMF) has become a widely used blind source separation technique due to its part based representation and ease of interpretability. We currently extend the NMF model to allow for delays between sources and sensors. This is a natural extension for spectrometry data...

  6. Comprehension of Action Negation Involves Inhibitory Simulation

    Directory of Open Access Journals (Sweden)

    Francesco eForoni

    2013-05-01

    Full Text Available Previous research suggests that action language is comprehended by activating the motor system. We report a study, investigating a critical question in this research field: Do negative sentences activate the motor system? Participants were exposed to sentences in the affirmation and negation forms while the zygomatic muscle activity on the left side of the face was continuously measured (Electromyography technique: EMG. Sentences were descriptions of emotional expressions that mapped either directly upon the zygomatic muscle (e.g., ‘I am smiling’ or did not (e.g., ‘I am frowning’. Reading sentences involving the negation of the activity of a specific muscle (zygomatic major - I am not smiling is shown to lead to the inhibition of this muscle. Reading sentences involving the affirmative form instead (I am smiling leads to the activation of zygomatic mucle. In contrast, sentences describing an activity that is irrelevant to the zygomatic muscle (e.g., ‘I am frowning’ or ‘I am not frowning’ produce no muscle activity. These results extend the range of simulation models to negation and by implication to an abstract domain. We discuss how this research contributes to the grounding of abstract and concrete concepts.

  7. The negative brain scintiscan in brain tumours

    International Nuclear Information System (INIS)

    Dalke, K.G.

    1978-01-01

    On the basis of 53 histologically verified and two histologically unidentified brain tumours, the author examined the reasons for these wrongly negative scintiscans. EEGs and angiographies carried out at about the same time were taken into account and compared with the scintigraphic findings. (orig.) [de

  8. 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…

  9. Autoconditioning system for BNL negative ion sources

    International Nuclear Information System (INIS)

    Larson, R.A.

    1979-01-01

    The autoconditioning system at BNL is being used to condition negative ion sources now under development. A minicomputer with appropriate interface hardware is employed to implement simple algorithims, slowly increasing the operating point of the source. This paper gives a brief description of the hardware and the software system

  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. An Interpersonal Approach to Writing Negative Messages.

    Science.gov (United States)

    Salerno, Douglas

    1988-01-01

    Asserts that textbook advice regarding buffers and negative messages is simplistic and frequently wrong, and analyses 22 job-refusal letters and their effectiveness. Claims that recent research on cognitive complexity and social perspective-taking suggests the need for more sophisticated audience analysis protocols for dealing with the negative…

  12. Attribution of Negative Intention in Williams Syndrome

    Science.gov (United States)

    Godbee, Kali; Porter, Melanie A.

    2013-01-01

    People with Williams syndrome (WS) are said to have sociable and extremely trusting personalities, approaching strangers without hesitation. This study investigated whether people with WS are less likely than controls to attribute negative intent to others when interpreting a series of ambiguous pictures. This may, at least partially, explain…

  13. Variations of Negative Pressure Wound Therapy

    African Journals Online (AJOL)

    a living reaction which serves to eradicate necrotic tissue and suppress bacterial propagation. In order to gain maximum advantages from NPWT, not only the negative pressure environment, but also the selection of the most suitable dressing material will be necessary. Regarding the treatment of diabetic foot ulcers, there.

  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. Constraints on negative-energy fluxes

    International Nuclear Information System (INIS)

    Ford, L.H.

    1991-01-01

    Locally negative energy due to quantum coherence effects in quantum field theory is discussed. In a previous work, it was argued that a beam carrying negative energy must satisfy an uncertainty-principle-type inequality of the form |ΔE|Δt≤1, where |ΔE| is the magnitude of the negative energy that may be transmitted in a time Δt. This conclusion applied only to two-dimensional spacetime, and was based on an examination of particular classes of quantum states. In the present work, we give more precise formulations of this type of inequality for a free massless scalar field in both two- and four-dimensional flat spacetime. These inequalities are proven to hold for all quantum states. The physical interpretation of these inequalities is also discussed, and it is argued that they are likely to prevent negative energy from producing such large-scale effects as violations of the second law of thermodynamics or of cosmic censorship

  16. THE SISYPHEAN MYTH, NEGATIVE CAPABILITY AND SOCIETAL ...

    African Journals Online (AJOL)

    mycl

    Capability suggest solutions to Camus' Sisyphean problem and its ilk. This paper explores this ... Framed us in jest, and left us now to hazardry? ... and right'; this being one half of a saying meant to create value for a soldier's sacrifice of his ... Keats made an interesting observation and propounded the theory of. 'Negative ...

  17. Advanced damper with negative structural stiffness elements

    International Nuclear Information System (INIS)

    Dong, Liang; Lakes, Roderic S

    2012-01-01

    Negative stiffness is understood as the occurrence of a force in the same direction as the imposed deformation. Structures and composites with negative stiffness elements enable a large amplification in damping. It is shown in this work, using an experimental approach, that when a flexible flat-ends column is aligned in a post-buckled condition, a negative structural stiffness and large hysteresis (i.e., high damping) can be achieved provided the ends of the column undergo tilting from flat to edge contact. Stable axial dampers with initial modulus equivalent to that of the parent material and with enhanced damping were designed and built using constrained negative stiffness effects entailed by post-buckled press-fit flat-ends columns. Effective damping of approximately 1 and an effective stiffness–damping product of approximately 1.3 GPa were achieved in such stable axial dampers consisting of PMMA columns. This is a considerable improvement for this figure of merit (i.e., the stiffness–damping product), which generally cannot exceed 0.6 GPa for currently used damping layers. (paper)

  18. When Depressive Cognitions Reflect Negative Realities.

    Science.gov (United States)

    Krantz, Susan E.

    The cognitive model of depression postulates that the depressed individual's cognitions are not only negative, but erroneous and impervious to information from the environment. However, the valence of that information ultimately determines whether those cognitions are impervious or merely receptive. The actual life circumstances of the depressed…

  19. Negative ion beam extraction in ROBIN

    International Nuclear Information System (INIS)

    Bansal, Gourab; Gahlaut, Agrajit; Soni, Jignesh; Pandya, Kaushal; Parmar, Kanu G.; Pandey, Ravi; Vuppugalla, Mahesh; Prajapati, Bhavesh; Patel, Amee; Mistery, Hiren; Chakraborty, Arun; Bandyopadhyay, Mainak; Singh, Mahendrajit J.; Phukan, Arindam; Yadav, Ratnakar K.; Parmar, Deepak

    2013-01-01

    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 12 cm −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 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 11 cm −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

  20. 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.

  1. Negative spiral CT in acute pulmonary embolism

    Energy Technology Data Exchange (ETDEWEB)

    Nilsson, T.; Olausson, A. [Karolinska Hospital, Stockholm (Sweden). Dept. of Thoracic Radiology; Johnsson, H. [Karolinska Hospital, Stockholm (Sweden). Dept. of Internal Medicine; Nyman, U. [County Hospital, Trelleborg (Sweden). Dept. of Radiology; Aspelin, P. [Huddinge Univ. Hospital (Sweden). Dept. of Radiology

    2002-09-01

    Purpose: To retrospectively evaluate the clinical outcome of non-anticoagulated patients with clinically suspected acute pulmonary embolism (PE) and no symptoms or signs of deep venous thrombosis (DVT) following a negative contrast medium-enhanced spiral CT of the pulmonary arteries (s-CTPA). Material and Methods: During a 24-month period, 739 of 751 patients underwent s-CTPA with acceptable diagnostic quality for clinically suspected acute PE. All patients who had a CT study not positive for PE were followed up with a questionnaire, a telephone interview and review of all medical reports, including autopsies and death certificates for any episodes of venous thromboembolism (VTE) during a 3-month period. Results: PE was diagnosed in 158 patients. Of the remaining 581 patients with a negative s-CTPA, 45 patients were lost to follow-up. 88 patients were excluded because of anticoagulation treatment (cardiac disorder n=32, chronic VTE or acute symptomatic DVT n=31, PE diagnosed at pulmonary angiography n=1, thrombus prophylaxis during diagnostic work-up or other reasons than VTE n=24) and 7 patients undergoing lower extremity venous studies because of symptoms of DVT (all negative). Thus, 441 patients with a negative s-CTPA and no DVT symptoms, venous studies or anticoagulant treatment constituted the follow-up cohort. Four of these patients had proven VTE (all PE) during the 3-month follow-up period. Two of the PE episodes contributed to the patient's death. Conclusion: Patients with clinically suspected acute PE, no symptoms or signs of DVT and a negative single slice s-CTPA using 3-5 mm collimation, may safely be left without anticoagulation treatment unless they are critically ill, have a limited cardiopulmonary reserve and/or if a high clinical suspicion remains.

  2. Schizophrenia and smoking: impact on negative symptoms

    Directory of Open Access Journals (Sweden)

    Miriam Saliba

    2017-06-01

    Full Text Available Introduction: it has been hypothesized that individuals with schizophrenia use nicotine to reduce negative symptoms and improve cognitive function. There is an inconsistency in the literature suggesting that nicotine could help decrease negative symptoms in schizophrenic patients. Objective: to investigate the effects of nicotine on the expression of the negative symptoms in smokers and non-smokers with schizophrenia. Methods: a cross sectional study, conducted between April and August 2016, 100 inpatients with schizophrenia (54 smokers and 46 non-smokers diagnosed according to DSM-V, at Psychiatric Hospital of the Cross Lebanon, were compared to changes in clinical parameters using CDSS, PANSS, and nicotine dependence using FTND. The Student’s t-test was used to compare between 2 groups, while the ANOVA test was used to compare between 3 or more groups. For categorical variables, the chi-2 test was used. Results: the mean age was 47.16 years (SD = 7.14 for smokers compared to 47.02 years (SD = 7.92 for non-smokers. 64.8% of smokers were males versus 45.7% of non-smokers. Smoking (high nicotine dependence significantly decreases the PANSS negative symptoms score between the 2 groups (p .05 for both variables. Discussion and conclusion: this study is the first to investigate the relationship between the expression of negative symptoms in individuals with schizophrenia and smoking in Lebanon. Cigarette smoking rates remain remarkably high in patients with schizophrenia. Smoking is a complex process which involves psychopathological, biochemical and neuropharmacological aspects among schizophrenic patients. Further studies are needed to acknowledge these findings and the reasons behind it.

  3. 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.

  4. 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

  5. Charging of dust grains in a plasma with negative ions

    International Nuclear Information System (INIS)

    Mamun, A.A.; Shukla, P.K.

    2003-01-01

    The role of negative ions on the charging of dust grains in a plasma is examined. Two models for negative ion distributions are considered. These are streaming negative ions and Boltzmannian negative ions. It is found that the effects of the negative ion number density, negative ion charge, and negative ion streaming speed significantly affect the dust grain surface potential or the dust grain charge

  6. Negation and negative information in the W3C resource description framework

    NARCIS (Netherlands)

    Analyti, A.; Antoniou, G.; Damásio, C.V.; Wagner, G.R.

    2004-01-01

    The concept of negation plays a special role in non-classical logics and also in knowledge representation formalisms where negative information has to be taken into account on par with positive information. In the tradition of mathematical logic, there is a general preference to consider positive

  7. On the lack of stranded negated quantifiers and inverse scope of negation in Romance

    NARCIS (Netherlands)

    Cirillo, R.

    2013-01-01

    The Germanic languages allow floating negated quantifiers (The children have not all not eaten) while the Romance languages do not. The Germanic languages also allow negation to take inverse scope over a universal quantifier (All the children have not eaten) whereas the Romance languages are very

  8. 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.

  9. Is the negative glow plasma of a direct current glow discharge negatively charged?

    International Nuclear Information System (INIS)

    Bogdanov, E. A.; Saifutdinov, A. I.; Demidov, V. I.; Kudryavtsev, A. A.

    2015-01-01

    A classic problem in gas discharge physics is discussed: what is the sign of charge density in the negative glow region of a glow discharge? It is shown that traditional interpretations in text-books on gas discharge physics that states a negative charge of the negative glow plasma are based on analogies with a simple one-dimensional model of discharge. Because the real glow discharges with a positive column are always two-dimensional, the transversal (radial) term in divergence with the electric field can provide a non-monotonic axial profile of charge density in the plasma, while maintaining a positive sign. The numerical calculation of glow discharge is presented, showing a positive space charge in the negative glow under conditions, where a one-dimensional model of the discharge would predict a negative space charge

  10. The positives of negative emotions: willingness to express negative emotions promotes relationships.

    Science.gov (United States)

    Graham, Steven M; Huang, Julie Y; Clark, Margaret S; Helgeson, Vicki S

    2008-03-01

    Four studies support the hypothesis that expressing negative emotion is associated with positive relationship outcomes, including elicitation of support, building of new close relationships, and heightening of intimacy in the closest of those relationships. In Study 1, participants read vignettes in which another person was experiencing a negative emotion. Participants reported they would provide more help when the person chose to express the negative emotion. In Study 2, participants watched a confederate preparing for a speech. Participants provided more help to her when she expressed nervousness. In Study 3, self-reports of willingness to express negative emotions predicted having more friends, controlling for demographic variables and extraversion. In Study 4, self-reports of willingness to express negative emotion measured prior to arrival at college predicted formation of more relationships, greater intimacy in the closest of those relationships, and greater received support from roommates across participants' first semester of college.

  11. Radiation quality of beams of negative pions

    International Nuclear Information System (INIS)

    Dicello, J.F.; Brenner, D.J.

    1981-01-01

    As a negative pion stops in tissue, it attaches itself to an adjacent atom to form a mesonic atom. Subsequently, the wave function of the pion interacts with that of the nucleus and the pion is absorbed. Because the energy associated with the rest mass of the pion is greater than the separation energy of the nuclear particles, the nucleus disintegrates (pion star). In tissue, approximately 40 MeV goes into overcoming the binding energies; 20 MeV goes into kinetic energy of charged particles; 80 MeV goes into kinetic energy of neutrons. In cases where biological studies are performed with beams of negative pions, as much as 20% of the total absorbed dose in the treatment volume and about 50% of the high-LET dose (> 100 keV/μm) can result from neutrons. The degree of biological response and the variation of that response throughout the treatment volume can be altered by the neutron dose

  12. 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.

  13. Negative electrodes for Na-ion batteries.

    Science.gov (United States)

    Dahbi, Mouad; Yabuuchi, Naoaki; Kubota, Kei; Tokiwa, Kazuyasu; Komaba, Shinichi

    2014-08-07

    Research interest in Na-ion batteries has increased rapidly because of the environmental friendliness of sodium compared to lithium. Throughout this Perspective paper, we report and review recent scientific advances in the field of negative electrode materials used for Na-ion batteries. This paper sheds light on negative electrode materials for Na-ion batteries: carbonaceous materials, oxides/phosphates (as sodium insertion materials), sodium alloy/compounds and so on. These electrode materials have different reaction mechanisms for electrochemical sodiation/desodiation processes. Moreover, not only sodiation-active materials but also binders, current collectors, electrolytes and electrode/electrolyte interphase and its stabilization are essential for long cycle life Na-ion batteries. This paper also addresses the prospect of Na-ion batteries as low-cost and long-life batteries with relatively high-energy density as their potential competitive edge over the commercialized Li-ion batteries.

  14. The production and destruction of negative ions

    International Nuclear Information System (INIS)

    Pegg, D.J.

    1991-01-01

    During the present grant period we are continuing our measurements of cross sections and asymmetry parameters for single photon-single electron detachment from atomic negative ions. In this period we have studied the stable ions B - and Li - . As a by product of these measurements we have investigated a new technique for measuring electron affinities. As in our previous work, we have made energy- and angle-resolved spectroscopic measurements of the yields and angular distributions of photoelectrons ejected at the intersection of perpendicularly crossed laser and negative ion beams. A combination of measurements of photoelectron yields, which are proportional to differential cross sections, and angular distributions allow us to determine angle-integrated cross sections for the photodetachment process. Cross sections for the inverse process of radiative attachment can be obtained from the photodetachment data by applying the principle of detailed balance

  15. Surface generation of negative hydrogen ion beams

    International Nuclear Information System (INIS)

    Bommel, P.J.M. van.

    1984-01-01

    This thesis describes investigations on negative hydrogen ion sources at the ampere level. Formation of H - ions occurs when positive hydrogen ions capture two electrons at metal surfaces. The negative ionization probability of hydrogen at metal surfaces increases strongly with decreasing work function of the surface. The converters used in this study are covered with cesium. Usually there are 'surface plasma sources' in which the hydrogen source plasma interacts with a converter. In this thesis the author concentrates upon investigating a new concept that has converters outside the plasma. In this approach a positive hydrogen ion beam is extracted from the plasma and is subsequently reflected from a low work function converter surface. (Auth.)

  16. Anomalous feedback and negative domain wall resistance

    International Nuclear Information System (INIS)

    Cheng, Ran; Xiao, Di; Zhu, Jian-Gang

    2016-01-01

    Magnetic induction can be regarded as a negative feedback effect, where the motive-force opposes the change of magnetic flux that generates the motive-force. In artificial electromagnetics emerging from spintronics, however, this is not necessarily the case. By studying the current-induced domain wall dynamics in a cylindrical nanowire, we show that the spin motive-force exerting on electrons can either oppose or support the applied current that drives the domain wall. The switching into the anomalous feedback regime occurs when the strength of the dissipative torque β is about twice the value of the Gilbert damping constant α . The anomalous feedback manifests as a negative domain wall resistance, which has an analogy with the water turbine. (paper)

  17. Emotionally Negative Pictures Enhance Gist Memory

    OpenAIRE

    Bookbinder, S. H.; Brainerd, C. J.

    2016-01-01

    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 due to valence and which are due to 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 reve...

  18. Analytical characterization of the genuine multiparticle negativity

    International Nuclear Information System (INIS)

    Hofmann, Martin; Moroder, Tobias; Gühne, Otfried

    2014-01-01

    The genuine multiparticle negativity is a measure of genuine multiparticle entanglement which can be numerically calculated. We present several results of how this entanglement measure can be characterized in an analytical way. First, we show that with an appropriate normalization this measure can be seen as coming from a mixed convex roof construction. Based on this, we determine its value for n-qubit GHZ-diagonal states and four-qubit cluster-diagonal states. (paper)

  19. 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.

  20. The Binomial Coefficient for Negative Arguments

    OpenAIRE

    Kronenburg, M. J.

    2011-01-01

    The definition of the binomial coefficient in terms of gamma functions also allows non-integer arguments. For nonnegative integer arguments the gamma functions reduce to factorials, leading to the well-known Pascal triangle. Using a symmetry formula for the gamma function, this definition is extended to negative integer arguments, making the symmetry identity for binomial coefficients valid for all integer arguments. The agreement of this definition with some other identities and with the bin...

  1. Comment on 'Perfect imaging without negative refraction'

    Science.gov (United States)

    Blaikie, R. J.

    2010-05-01

    The prediction of 'perfect' imaging without negative refraction for Maxwell's fish-eye lens (Leonhardt U 2009 New J. Phys. 11 093040) is a consequence of imposing an active localized 'drain' at the image point rather than being a general property of the lens. This work then becomes analogous to other work using time-reversal symmetry and/or structured antennae to achieve super-resolution, which can be applied to many types of imaging system beyond the fish-eye lens.

  2. Comment on 'Perfect imaging without negative refraction'

    International Nuclear Information System (INIS)

    Blaikie, R J

    2010-01-01

    The prediction of 'perfect' imaging without negative refraction for Maxwell's fish-eye lens (Leonhardt U 2009 New J. Phys. 11 093040) is a consequence of imposing an active localized 'drain' at the image point rather than being a general property of the lens. This work then becomes analogous to other work using time-reversal symmetry and/or structured antennae to achieve super-resolution, which can be applied to many types of imaging system beyond the fish-eye lens.

  3. Negative parity non-strange baryons

    International Nuclear Information System (INIS)

    Stancu, F.; Stassart, P.

    1991-01-01

    Our previous study is extended to negative parity baryon resonances up to J=(9/2) - . The framework is a semi-relativistic constituent quark model. The quark-quark interaction contains a Coulomb plus linear confinement terms and a short distance spin-spin and tensor terms. It is emphasized that a linear confinement potential gives too large a mass to the D 35 (1930) resonance. (orig.)

  4. Biphase sinusoidal oscillator based on negative resistor.

    Science.gov (United States)

    Bayard, Jean

    2010-06-01

    This paper describes a biphase sinusoidal generator which provides two signals: v(ref)=V(M) sin(omegat) and v(out)=V(M) sin(omegat+DeltaPhi), where DeltaPhi is in the range 0, pi/2 or -pi/2, 0 and is not dependent on the frequency value. It is based on a negative resistor and it requires very few components. SPICE simulations and measurements on an experimental setup confirm the theoretical analysis.

  5. Photodetachment of negative C60- ions

    International Nuclear Information System (INIS)

    Amusia, M.Ya.; Baltenkov, A.S.; Krakov, B.G.

    1998-01-01

    A model that describes the electron structure of negative fullerene C 60 - ions is proposed. The model contains only two experimentally observed parameters, namely the fullerene radius and the affinity energy of the electron to neutral C 60 . In the frame of this model, cross sections are calculated of elastic scattering of slow electrons on neutral fullerene, of C 60 - photodetachment near the threshold of this process and of radiative recombination of slow electrons with neutral fullerenes. (orig.)

  6. Collective phenomena in negative ion photodetachment

    International Nuclear Information System (INIS)

    Ivanov, V.K.

    1996-01-01

    The many-electron collective effects in negative ion photodetachment are discussed. The calculations of photodetachment cross sections and photoelectron angular distributions have been performed within the Many-Body Theory Methods. It is shown that the role of many-electron interactions leading to the collective effects like dynamical polarizability, interchannel interaction, core polarization, core relaxation, is very important to describe the photodetachment processes. (author)

  7. Local behaviour of negative thermal expansion materials

    International Nuclear Information System (INIS)

    Fornasini, P.; Dalba, G.; Grisenti, R.; Purans, J.; Vaccari, M.; Rocca, F.; Sanson, A.

    2006-01-01

    EXAFS can represent a powerful probe of the local behaviour of negative thermal expansion (NTE) materials, thanks to the possibility of measuring the expansion of selected inter-atomic bonds and the perpendicular relative atomic displacements. The effectiveness of EXAFS for NTE studies is illustrated by a comparison of results recently obtained on germanium, CuCl and the cuprites Cu 2 O and Ag 2 O

  8. Plasma Beam Interaction with Negative glow discharge

    International Nuclear Information System (INIS)

    El-Tayeb, H.A.; El-Gamal, H.A.

    2000-01-01

    A miniature coaxial gun has been used to study the effect of the energy spectrum of the ejected plasma on the interaction with negative glow region in a normal glow discharge. The peak discharge current flow between the coaxial electrodes was 5.25 K A as a single pulse with pulse duration of 60 MUs. Investigations are carried out with argon gas at pressure 0.4 Torr. The sheath thickness of the ejected plasma from the coaxial discharge was 6 cm with different densities and energies. The spectrum of electron energy varies between 6 eV and 1 eV, while the electron density varies between 5 x 10 12 cm -3 and 4x10 13 cm -3 . The peak velocity of the ejected plasma was 0. 8 x 10 5 cm sec -1 in the neutral argon atoms. Argon negative glow region used as base plasma has an electron temperature of 2.2 eV and electron density of 6.2 x10 7 cm -3 . It had been found that the velocity of the ejected plasma decreased when it moves in the negative glow region and its mean electron temperature decreased. The results are compared with the theory of beam interaction with cold plasma

  9. Excited negative parity bands in 160Yb

    Science.gov (United States)

    Saha, A.; Bhattacharjee, T.; Curien, D.; Dedes, I.; Mazurek, K.; Banerjee, S. R.; Rajbanshi, S.; Bisoi, A.; de Angelis, G.; Bhattacharya, Soumik; Bhattacharyya, S.; Biswas, S.; Chakraborty, A.; Das Gupta, S.; Dey, B.; Goswami, A.; Mondal, D.; Pandit, D.; Palit, R.; Roy, T.; Singh, R. P.; Saha Sarkar, M.; Saha, S.; Sethi, J.

    2018-03-01

    Negative parity rotational bands in {} 70160Yb{}90 nucleus have been studied. They were populated in the 148Sm(16O, 4n)160Yb reaction at 90 MeV. The gamma-coincidence data have been collected using Indian National Gamma Array composed of twenty Compton suppressed clover germanium (Ge) detectors. Double gating on triple gamma coincidence data were selectively used to develop the decay scheme for these negative parity bands by identifying and taking care of the multiplet transitions. The even- and odd-spin negative parity bands in 160Yb have been studied by comparing the reduced transition probability ratios with the similar bands in neighbouring even-even rare earth nuclei. It is concluded that the concerned odd-spin and even-spin bands are not signature partners and that their structures are compatible with those of the ‘pear-shape’ and ‘pyramid-shape’ oscillations, respectively, the octupole shapes superposed with the quadrupole shape of the ground-state.

  10. 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.

  11. 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.

  12. LIFE EVENTS AND NEGATIVE RELIGIOUS COPING

    Directory of Open Access Journals (Sweden)

    sema eryücel

    2013-06-01

    Full Text Available 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.

  13. 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.

  14. Negative Halogen Ions for Fusion Applications

    International Nuclear Information System (INIS)

    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

  15. On the negative resistance of double layers

    International Nuclear Information System (INIS)

    Raadu, M.A.; Silevitch, M.B.

    1982-08-01

    It is known that large amplitudes oscillations can occur in the current flowing through a plasma diode, typically when a constant potential is applied across the device. Burger (1965) suggested via a computer simulation that the oscillation characteristics was a function of the quantities T sub (e) and T sub (i), namely the respective time for an electron and an ion to cross the electric field region inside the diode. On the rapid time scale T sub (e) the self consistent equilibrium configuration, was unstable. Norris (1964) had previously arrived at the same conclusion using analytical arguments. In that work, it was concluded that the instability occurred since the diode acted as a negative resistance on the T sub (e) scale. A positive feedback effect forced the system away from equilibrium. Silevitch (1981) used the Burger mechanism to suggest an explanation for the flickering aurora phenomenon. He extended the Norris argument and showed by a variational method that a plausible analytic model for a double layer (DL) behaved as a negative resistance on the T sub (e) scale. In this present work we re-examine the negative resistance calculation by taking a more detailed account of the constraints which are imposed on the electron distributions that exist in the DL region. Specifically, we shall focus at the high potential side of the DL. (Authors)

  16. A computational approach to negative priming

    Science.gov (United States)

    Schrobsdorff, H.; Ihrke, M.; Kabisch, B.; Behrendt, J.; Hasselhorn, M.; Herrmann, J. Michael

    2007-09-01

    Priming is characterized by a sensitivity of reaction times to the sequence of stimuli in psychophysical experiments. The reduction of the reaction time observed in positive priming is well-known and experimentally understood (Scarborough et al., J. Exp. Psycholol: Hum. Percept. Perform., 3, pp. 1-17, 1977). Negative priming—the opposite effect—is experimentally less tangible (Fox, Psychonom. Bull. Rev., 2, pp. 145-173, 1995). The dependence on subtle parameter changes (such as response-stimulus interval) usually varies. The sensitivity of the negative priming effect bears great potential for applications in research in fields such as memory, selective attention, and ageing effects. We develop and analyse a computational realization, CISAM, of a recent psychological model for action decision making, the ISAM (Kabisch, PhD thesis, Friedrich-Schiller-Universitat, 2003), which is sensitive to priming conditions. With the dynamical systems approach of the CISAM, we show that a single adaptive threshold mechanism is sufficient to explain both positive and negative priming effects. This is achieved by comparing results obtained by the computational modelling with experimental data from our laboratory. The implementation provides a rich base from which testable predictions can be derived, e.g. with respect to hitherto untested stimulus combinations (e.g. single-object trials).

  17. Thyroid antibody-negative euthyroid Graves’ ophthalmopathy

    Directory of Open Access Journals (Sweden)

    Arshiya Tabasum

    2016-06-01

    Full Text Available TSH receptor antibodies (TRAbs are the pathological hallmark of Graves’ disease, present in nearly all patients with the disease. Euthyroid Graves’ ophthalmopathy (EGO is a well-recognized clinical entity, but its occurrence in patients with negative TRAbs is a potential source of diagnostic confusion. A 66-year-old female presented to our endocrinology clinic with right eye pain and diplopia in the absence of thyroid dysfunction. TRAbs were negative, as measured with a highly sensitive third-generation thyrotropin-binding inhibitory immunoglobulin (TBII ELISA assay. CT and MRI scans of the orbit showed asymmetrical thickening of the inferior rectus muscles but no other inflammatory or malignant orbital pathology. Graves’ ophthalmopathy (GO was diagnosed on the basis of the clinical and radiological features, and she underwent surgical recession of the inferior rectus muscle with complete resolution of the diplopia and orbital pain. She remained euthyroid over the course of follow-up but ultimately developed overt clinical and biochemical hyperthyroidism, 24 months after the initial presentation. By this time, she had developed positive TRAb as well as thyroid peroxidase antibodies. She responded to treatment with thionamides and remains euthyroid. This case highlights the potential for negative thyroid-specific autoantibodies in the presentation of EGO and underscores the variable temporal relationship between the clinical expression of thyroid dysfunction and orbital disease in the natural evolution of Graves’ disease.

  18. Negative density-distribution relationship in butterflies.

    Science.gov (United States)

    Päivinen, Jussi; Grapputo, Alessandro; Kaitala, Veijo; Komonen, Atte; Kotiaho, Janne S; Saarinen, Kimmo; Wahlberg, Niklas

    2005-03-01

    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. 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. 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. Negative Mood Increases Selective Attention to Negatively Valenced Body Parts in Female Adolescents with Anorexia Nervosa.

    Directory of Open Access Journals (Sweden)

    Jennifer Svaldi

    Full Text Available 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.

  20. Turning negative into positive: public health mass media campaigns and negative advertising.

    Science.gov (United States)

    Apollonio, D E; Malone, R E

    2009-06-01

    Literature suggests that 'negative advertising' is an effective way to encourage behavioral changes, but it has enjoyed limited use in public health media campaigns. However, as public health increasingly focuses on non-communicable disease prevention, negative advertising could be more widely applied. This analysis considers an illustrative case from tobacco control. Relying on internal tobacco industry documents, surveys and experimental data and drawing from political advocacy literature, we describe tobacco industry and public health research on the American Legacy Foundation's "truth" campaign, an example of effective negative advertising in the service of public health. The tobacco industry determined that the most effective advertisements run by Legacy's "truth" campaign were negative advertisements. Although the tobacco industry's own research suggested that these negative ads identified and effectively reframed the cigarette as a harmful consumer product rather than focusing solely on tobacco companies, Philip Morris accused Legacy of 'vilifying' it. Public health researchers have demonstrated the effectiveness of the "truth" campaign in reducing smoking initiation. Research on political advocacy demonstrating the value of negative advertising has rarely been used in the development of public health media campaigns, but negative advertising can effectively communicate certain public health messages and serve to counter corporate disease promotion.

  1. Experimental Evaluation of a Negative Ion Source for a Heavy Ion Fusion Negative Ion Driver

    International Nuclear Information System (INIS)

    Grisham, L.R.; Hahto, S.K.; Hahto, S.T.; Kwan, J.W.; Leung, K.N.

    2004-01-01

    Negative halogen ions have recently been proposed as a possible alternative to positive ions for heavy ion fusion drivers because electron accumulation would not be a problem in the accelerator, and if desired, the beams could be photo-detached to neutrals. To test the ability to make suitable quality beams, an experiment was conducted at Lawrence Berkeley National Laboratory using chlorine in an RF-driven ion source. Without introducing any cesium (which is required to enhance negative ion production in hydrogen ion sources) a negative chlorine current density of 45 mA/cm 2 was obtained under the same conditions that gave 57 45 mA/cm 2 of positive chlorine, suggesting the presence of nearly as many negative ions as positive ions in the plasma near the extraction plane. The negative ion spectrum was 99.5% atomic chlorine ions, with only 0.5% molecular chlorine, and essentially no impurities. Although this experiment did not incorporate the type of electron suppression technology that i s used in negative hydrogen beam extraction, the ratio of co-extracted electrons to Cl - was as low as 7 to 1, many times lower than the ratio of their mobilities, suggesting that few electrons are present in the near-extractor plasma. This, along with the near-equivalence of the positive and negative ion currents, suggests that the plasma in this region was mostly an ion-ion plasma. The negative chlorine current density was relatively insensitive to pressure, and scaled linearly with RF power. If this linear scaling continues to hold at higher RF powers, it should permit current densities of 100 45 mA/cm 2 , sufficient for present heavy ion fusion injector concepts. The effective ion temperatures of the positive and negative ions appeared to be similar and relatively low for a plasma source

  2. How does "not left" become "right"? Electrophysiological evidence for a dynamic conflict-bound negation processing account.

    Science.gov (United States)

    Dudschig, Carolin; Kaup, Barbara

    2018-05-01

    Human thought and language is traditionally considered as abstract, amodal, and symbolic. However, recent theories propose that high-level human cognition is directly linked to basic, modal biological systems such as sensorimotor areas. Despite this influential representational debate very little is known regarding whether the mechanisms involved in sensorimotor control are also shared with higher-level cognitive processes, such as language comprehension. We investigated negation as a universal of human language, addressing two key questions: (a) Does negation result in a conflict-like representation? (b) Does negation trigger executive control adjustments in a similar manner as standard information processing conflicts do (e.g., Simon, Flanker)? Electrophysiological data indicated that phrases such as "not left/not right" result in initial activation of the to-be-negated information and subsequently the outcome of the negation process. More importantly, our findings also suggest that negation triggers conflict-related adjustments in information processing in line with traditional conflict tasks. Trial-by-trial conflict adaptation patterns in both behavioral and electrophysiological data indicated that negation processing dynamically changes depending on the current cognitive state. In summary, negation processing results in cognitive conflict, and dynamic influences of the cognitive state determine conflict resolution, that is, negation implementation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  3. Human Respiratory Syncytial Virus and Human Metapneumovirus

    OpenAIRE

    Luciana Helena Antoniassi da Silva; Fernando Rosado Spilki; Adriana Gut Lopes Riccetto; Emilio Elias Baracat; Clarice Weis Arns

    2009-01-01

    The human respiratory syncytial virus (hRSV) and the human metapneumovírus (hMPV) are main etiological agents of acute respiratory infections (ARI). The ARI is an important cause of childhood morbidity and mortality worldwide.  hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV) is the best characterized agent viral of this group, associated with respiratory diseases in...

  4. Distinct microbiological signatures associated with triple negative breast cancer.

    Science.gov (United States)

    Banerjee, Sagarika; Wei, Zhi; Tan, Fei; Peck, Kristen N; Shih, Natalie; Feldman, Michael; Rebbeck, Timothy R; Alwine, James C; Robertson, Erle S

    2015-10-15

    Infectious agents are the third highest human cancer risk factor and may have a greater role in the origin and/or progression of cancers, and related pathogenesis. Thus, knowing the specific viruses and microbial agents associated with a cancer type may provide insights into cause, diagnosis and treatment. We utilized a pan-pathogen array technology to identify the microbial signatures associated with triple negative breast cancer (TNBC). This technology detects low copy number and fragmented genomes extracted from formalin-fixed paraffin embedded archival tissues. The results, validated by PCR and sequencing, define a microbial signature present in TNBC tissue which was underrepresented in normal tissue. Hierarchical clustering analysis displayed two broad microbial signatures, one prevalent in bacteria and parasites and one prevalent in viruses. These signatures demonstrate a new paradigm in our understanding of the link between microorganisms and cancer, as causative or commensal in the tumor microenvironment and provide new diagnostic potential.

  5. 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.

  6. Perceived social pressure not to experience negative emotion is linked to selective attention for negative information.

    Science.gov (United States)

    Bastian, Brock; Pe, Madeline Lee; Kuppens, Peter

    2017-02-01

    Social norms and values may be important predictors of how people engage with and regulate their negative emotional experiences. Previous research has shown that social expectancies (the perceived social pressure not to feel negative emotion (NE)) exacerbate feelings of sadness. In the current research, we examined whether social expectancies may be linked to how people process emotional information. Using a modified classical flanker task involving emotional rather than non-emotional stimuli, we found that, for those who experienced low levels of NE, social expectancies were linked to the selective avoidance of negative emotional information. Those who experienced high levels of NE did not show a selective avoidance of negative emotional information. The findings suggest that, for people who experience many NEs, social expectancies may lead to discrepancies between how they think they ought to feel and the kind of emotional information they pay attention to.

  7. Neural correlates of attitude change following positive and negative advertisements

    Directory of Open Access Journals (Sweden)

    Junko Kato

    2009-05-01

    Full Text Available Understanding changes in attitudes towards others is critical to understanding human behaviour. Neuropolitical studies have found that the activation of emotion-related areas in the brain is linked to resilient political preferences, and neuroeconomic research has analysed the neural correlates of social preferences that favour or oppose consideration of intrinsic rewards. This study aims to identify the neural correlates in the prefrontal cortices of changes in political attitudes toward others that are linked to social cognition. Functional magnetic resonance imaging (fMRI experiments have presented videos from previous electoral campaigns and television commercials for major cola brands and then used the subjects’ self-rated affinity toward political candidates as behavioural indicators. After viewing negative campaign videos, subjects showing stronger fMRI activation in the dorsolateral prefrontal cortex lowered their ratings of the candidate they originally supported more than did those with smaller fMRI signal changes in the same region. Subjects showing stronger activation in the medial prefrontal cortex tended to increase their ratings more than did those with less activation. The same regions were not activated by viewing negative advertisements for cola. Correlations between the self-rated values and the neural signal changes underscore the metric representation of observed decisions (i.e., whether to support or not in the brain. This indicates that neurometric analysis may contribute to the exploration of the neural correlates of daily social behaviour.

  8. Negative outcomes evoke cyclic irrational decisions in Rock, Paper, Scissors.

    Science.gov (United States)

    Dyson, Benjamin James; Wilbiks, Jonathan Michael Paul; Sandhu, Raj; Papanicolaou, Georgios; Lintag, Jaimie

    2016-02-04

    Rock, Paper, Scissors (RPS) represents a unique gaming space in which the predictions of human rational decision-making can be compared with actual performance. Playing a computerized opponent adopting a mixed-strategy equilibrium, participants revealed a non-significant tendency to over-select Rock. Further violations of rational decision-making were observed using an inter-trial analysis where participants were more likely to switch their item selection at trial n + 1 following a loss or draw at trial n, revealing the strategic vulnerability of individuals following the experience of negative rather than positive outcome. Unique switch strategies related to each of these trial n outcomes were also identified: after losing participants were more likely to 'downgrade' their item (e.g., Rock followed by Scissors) but after drawing participants were more likely to 'upgrade' their item (e.g., Rock followed by Paper). Further repetition analysis revealed that participants were more likely to continue their specific cyclic item change strategy into trial n + 2. The data reveal the strategic vulnerability of individuals following the experience of negative rather than positive outcome, the tensions between behavioural and cognitive influences on decision making, and underline the dangers of increased behavioural predictability in other recursive, non-cooperative environments such as economics and politics.

  9. 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.

  10. The RNA synthesis machinery of negative-stranded RNA viruses

    International Nuclear Information System (INIS)

    Ortín, Juan; Martín-Benito, Jaime

    2015-01-01

    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

  11. Neural Correlates of Attitude Change Following Positive and Negative Advertisements

    Science.gov (United States)

    Kato, Junko; Ide, Hiroko; Kabashima, Ikuo; Kadota, Hiroshi; Takano, Kouji; Kansaku, Kenji

    2009-01-01

    Understanding changes in attitudes towards others is critical to understanding human behaviour. Neuropolitical studies have found that the activation of emotion-related areas in the brain is linked to resilient political preferences, and neuroeconomic research has analysed the neural correlates of social preferences that favour or oppose consideration of intrinsic rewards. This study aims to identify the neural correlates in the prefrontal cortices of changes in political attitudes toward others that are linked to social cognition. Functional magnetic resonance imaging (fMRI) experiments have presented videos from previous electoral campaigns and television commercials for major cola brands and then used the subjects' self-rated affinity toward political candidates as behavioural indicators. After viewing negative campaign videos, subjects showing stronger fMRI activation in the dorsolateral prefrontal cortex lowered their ratings of the candidate they originally supported more than did those with smaller fMRI signal changes in the same region. Subjects showing stronger activation in the medial prefrontal cortex tended to increase their ratings more than did those with less activation. The same regions were not activated by viewing negative advertisements for cola. Correlations between the self-rated values and the neural signal changes underscore the metric representation of observed decisions (i.e., whether to support or not) in the brain. This indicates that neurometric analysis may contribute to the exploration of the neural correlates of daily social behaviour. PMID:19503749

  12. Formation of hydrogen negative ions by surface and volume processes with application to negative ion sources

    International Nuclear Information System (INIS)

    Hiskes, J.R.

    1979-01-01

    During the last few decades interest in negative-hydrogen ion sources has been directed mainly toward synchrotron and other particle accelerator applications, with emphasis on high current densities delivered for short pulses. But within the last several years there has been an awareness in the magnetic fusion program of the future need for negative ions as a means for generating high energy neutral beams, beams with energies above a few hundred keV. Negative ions seem to be the only effective intermediary for efficiently producing such beams. Although methods for generating negative ion beams have relied upon synchrotron concepts, the requirements for fusion are very different: here one is interested in more moderate current densities, up to 100 m A cm -2 , but with continuous operation. Proposed source modules would accelerate of the order of 10 A of beam current and deliver several megawatts of beam power. Both H - and D - beams are being considered for application in different reactor systems. The conceptualization of negative ion sources is now in a very volatile stage. But of the great variety of proposals that have been offered to date, three general areas appear ready for development. These are: first, the double charge exchange method for converting a positive ion beam into a negative ion beam; second, electron-volume processes wherein low energy electrons interacting with molecular species lead to negative ion products via dissociative attachment or recombination; and third, generation of negative ions in surface interactions, principally via desorption and backscattering. Both our qualitative and our quantitative understanding of these processes diminishes as one proceeds from the first through the third. The physics of these three methods is considered in detail

  13. Exchange rate behavior with negative interest rates: Some early negative observations

    OpenAIRE

    Hameed, Allaudeen S.; Rose, Andrew

    2017-01-01

    This paper examines exchange rate behavior during the recent period with negative nominal interest rates. We use a daily panel of data on 61 currencies from January 2010 through May 2016, during which five economies - Denmark, the European Economic and Monetary Union, Japan, Sweden, and Switzerland - experienced negative nominal interest rates. We examine both effective exchange rates and bilateral rates; the latter typically measured against the Swiss franc since Switzerland has had the long...

  14. 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.

  15. Pathways to Carbon-Negative Liquid Biofuels

    Science.gov (United States)

    Woolf, D.; Lehmann, J.

    2017-12-01

    Many climate change mitigation scenarios assume that atmospheric carbon dioxide removal will be delivered at scale using bioenergy power generation with carbon capture and storage (BECCS). However, other pathways to negative emission technologies (NETs) in the energy sector are possible, but have received relatively little attention. Given that the costs, benefits and life-cycle emissions of technologies vary widely, more comprehensive analyses of the policy options for NETs are critical. This study provides a comparative assessment of the potential pathways to carbon-negative liquid biofuels. It is often assumed that that decarbonisation of the transport sector will include use of liquid biofuels, particularly for applications that are difficult to electrify such as aviation and maritime transport. However, given that biomass and land on which to grow it sustainably are limiting factors in the scaling up of both biofuels and NETs, these two strategies compete for shared factors of production. One way to circumvent this competition is carbon-negative biofuels. Because capture of exhaust CO2 in the transport sector is impractical, this will likely require carbon capture during biofuel production. Potential pathways include, for example, capture of CO2 from fermentation, or sequestration of biochar from biomass pyrolysis in soils, in combination with thermochemical or bio-catalytic conversion of syngas to alcohols or alkanes. Here we show that optimal pathway selection depends on specific resource constraints. As land availability becomes increasingly limiting if bioenergy is scaled up—particularly in consideration that abandoned degraded land is widely considered to be an important resource that does not compete with food fiber or habitat—then systems which enhance land productivity by increasing soil fertility using soil carbon sequestration become increasingly preferable compared to bioenergy systems that deplete or degrade the land resource on which they

  16. 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.

  17. Unnaturalness of Negation – an Old Wives’ Tale Retold

    Directory of Open Access Journals (Sweden)

    Gašper Ilc

    2006-06-01

    Full Text Available Negation has a very long history of study. In the realm of logic, negation is seen as a simple operation that turns an affirmative to a negative. This assumption strongly affected the linguistic study of negation, and led to some misconceptions. For example, negation in natural languages is seen as something unnatural, artificial and syntactically as well as semantically dependant on affirmation. It is perceived as a logical/mathematical operation that turns affirmatives into negatives by way of syntactic transformation and semantic cancellation of multiple negatives. To refute some of these misconceptions, the paper investigates the nature of negation as a linguistic phenomenon, and shows that negation in logic and linguistics should not and cannot be treated in the same fashion. Special attention is paid to the problems of structural complexity, the syntactic notion of multiple negation and its different semantic interpretations. With regard to the semantic interpretation of multiple negation, languages, by and large, allow for two possibilities: negative concord and double negation. Negative concord, which interprets two negatives as a single negation, seems to represent the natural course of language development, while double negation, which allows the cancellation of two negatives resulting in affirmation, was introduced into languages under the influence of logic in the 17th and 18th centuries.

  18. If you negate, you may forget: negated repetitions impair memory compared with affirmative repetitions.

    Science.gov (United States)

    Mayo, Ruth; Schul, Yaacov; Rosenthal, Meytal

    2014-08-01

    One of the most robust laws of memory is that repeated activation improves memory. Our study shows that the nature of repetition matters. Specifically, although both negated repetition and affirmative repetition improve memory compared with no repetition, negated repetition hinders memory compared with affirmative repetition. After showing participants different entities, we asked them about features of these entities, leading to either "yes" or "no" responses. Our findings show that correctly negating an incorrect feature of an entity elicits an active forgetting effect compared with correctly affirming its true features. For example, after seeing someone drink a glass of white wine, answering "no" to "was it red wine?" may lead one to greater memory loss of the individual drinking wine at all compared with answering "yes" to "was it white wine?" We find this negation-induced forgetting effect in 4 experiments that differ in (a) the meaning given for the negation, (b) the type of stimuli (visual or verbal), and (c) the memory measure (recognition or free recall). We discuss possible underlying mechanisms and offer theoretical and applied implications of the negation-induced forgetting effect in relation to other known inhibition effects. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  19. Bimodality and negative heat capacity in multifragmentation

    International Nuclear Information System (INIS)

    Tamain, B.; Bougault, R.; Lopez, O.; Pichon, M.

    2003-01-01

    This contribution addresses the question of the possible link between multifragmentation and the liquid-gas phase transition of nuclear matter. Bi-modality seems to be a robust signal of this link in the sense that theoretical calculations indicate that it is preserved even if a sizeable fraction of the available energy has not been shared among all the degrees of freedom. The corresponding measured properties are coherent with what is expected in a liquid-gas phase transition picture. Moreover, bi-modality and negative heat capacity are observed for the same set of events. (authors)

  20. Negative pion capture in chemical compounds

    International Nuclear Information System (INIS)

    Butsev, V.S.; Chultem, D.; Gavrilov, Yu.K.; Ganzorig, Dz.; Norseev, Yu.V.; Presperin, V.

    1976-01-01

    The results are reported of an experiment of determination of the probability of capture of resting negative pions by iodine nuclei in alkali metal iodides (LiI, NaI, KI, RbI, CsI). The yield of an isomer sup(116m)(Sb/8 - ) with a high spin number, formed in the reaction 127 I(π - , lp 10n) allows to determine the relative probability of the nuclear capture of pions in the above compounds. The results obrained are compared with the predictions of the Fermi-Teller Z-law