Endogenous attention modulates attentional and motor interference from distractors: Evidence from behavioral and electrophysiological results.

Directory of Open Access Journals (Sweden)

Elisa eMartín-Arévalo

2015-02-01

Full Text Available Selective visual attention enhances the processing of relevant stimuli and filters out irrelevant stimuli and/or distractors. However, irrelevant information is sometimes processed, as demonstrated by the Simon effect (Simon & Rudell, 1967. We examined whether fully irrelevant distractors (task and target-irrelevant produce interference (measured as the Simon effect, and whether endogenous orienting modulated this interference. Despite being fully irrelevant, distractors were attentionally coded (as reflected by the distractor-related N2pc component, and interfered with the processing of the target response (as reflected by the target-related LRP component. Distractor’s attentional capture depended on endogenous attention, and their interference with target responses was modulated by both endogenous attention and distractor location repetition. These results demonstrate both endogenous attentional and motor modulations over the Simon effect produced by fully irrelevant distractors.

Recovery from Proactive Semantic Interference and MRI Volume: A Replication and Extension Study.

Science.gov (United States)

Loewenstein, David A; Curiel, Rosie E; DeKosky, Steven; Rosselli, Monica; Bauer, Russell; Grieg-Custo, Maria; Penate, Ailyn; Li, Chunfei; Lizagarra, Gabriel; Golde, Todd; Adjouadi, Malek; Duara, Ranjan

2017-01-01

The rise in incidence of Alzheimer's disease (AD) has led to efforts to advance early detection of the disease during its preclinical stages. To achieve this, the field needs to develop more sensitive cognitive tests that relate to biological markers of disease pathology. Failure to recover from proactive interference (frPSI) is one such cognitive marker that is associated with volumetric reductions in the hippocampus, precuneus, and other AD-prone regions, and to amyloid load in the brain. The current study attempted to replicate and extend our previous findings that frPSI is a sensitive marker of early AD, and related to a unique pattern of volumetric loss in AD prone areas. Three different memory measures were examined relative to volumetric loss and cortical thickness among 45 participants with amnestic mild cognitive impairment. frPSI was uniquely associated with reduced volumes in the hippocampus (r = 0.50) precuneus (r = 0.41), and other AD prone regions, replicating previous findings. Strong associations between frPSI and lower entorhinal cortex volumes and cortical thickness (r≥0.60) and precuneus (r = 0.50) were also observed. Unique and strong associations between volumetric reductions and frPSI as observed by Loewenstein and colleagues were replicated. Together with cortical thickness findings, these results indicate that frPSI is worthy of further study as a sensitive and early cognitive marker of AD.

A novel interference mechanism by a type IIIB CRISPR-Cmr module in Sulfolobus

DEFF Research Database (Denmark)

Deng, Ling; Garrett, Roger Antony; Shah, Shiraz Ali

2013-01-01

Recent studies on CRISPR-based adaptive immune systems have revealed extensive structural and functional diversity of the interference complexes which often coexist intracellularly. The archaeon Sulfolobus islandicus REY15A encodes three interference modules, one of type IA and two of type IIIB...... targeting. A rationale is provided for the intracellular coexistence of the different interference systems in S.¿islandicus REY15A which cooperate functionally by sharing a single Cas6 protein for crRNA processing and utilize crRNA products from identical CRISPR spacers....

Emotion and sex of facial stimuli modulate conditional automaticity in behavioral and neuronal interference in healthy men.

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Kohn, Nils; Fernández, Guillén

2017-12-06

Our surrounding provides a host of sensory input, which we cannot fully process without streamlining and automatic processing. Levels of automaticity differ for different cognitive and affective processes. Situational and contextual interactions between cognitive and affective processes in turn influence the level of automaticity. Automaticity can be measured by interference in Stroop tasks. We applied an emotional version of the Stroop task to investigate how stress as a contextual factor influences the affective valence-dependent level of automaticity. 120 young, healthy men were investigated for behavioral and brain interference following a stress induction or control procedure in a counter-balanced cross-over-design. Although Stroop interference was always observed, sex and emotion of the face strongly modulated interference, which was larger for fearful and male faces. These effects suggest higher automaticity when processing happy and also female faces. Supporting behavioral patterns, brain data show lower interference related brain activity in executive control related regions in response to happy and female faces. In the absence of behavioral stress effects, congruent compared to incongruent trials (reverse interference) showed little to no deactivation under stress in response to happy female and fearful male trials. These congruency effects are potentially based on altered context- stress-related facial processing that interact with sex-emotion stereotypes. Results indicate that sex and facial emotion modulate Stroop interference in brain and behavior. These effects can be explained by altered response difficulty as a consequence of the contextual and stereotype related modulation of automaticity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Piper betle L. Modulates Senescence-Associated Genes Expression in Replicative Senescent Human Diploid Fibroblasts

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Lina Wati Durani

2017-01-01

Full Text Available Piper betle (PB is a traditional medicine that is widely used to treat different diseases around Asian region. The leaf extracts contain various bioactive compounds, which were reported to have antidiabetic, antibacterial, anti-inflammatory, antioxidant, and anticancer effects. In this study, the effect of PB aqueous extracts on replicative senescent human diploid fibroblasts (HDFs was investigated by determining the expressions of senescence-associated genes using quantitative PCR. Our results showed that PB extracts at 0.4 mg/ml can improve cell proliferation of young (143%, presenescent (127.3%, and senescent (157.3% HDFs. Increased expressions of PRDX6, TP53, CDKN2A, PAK2, and MAPK14 were observed in senescent HDFs compared to young and/or presenescent HDFs. Treatment with PB extracts modulates the transcriptional profile changes in senescent HDFs. By contrast, expressions of SOD1 increased, whereas GPX1, PRDX6, TP53, CDKN2A, PAK2, and MAPK14 were decreased in PB-treated senescent HDFs compared to untreated senescent HDFs. In conclusion, this study indicates the modulation of PB extracts on senescence-associated genes expression of replicative senescent HDFs. Further studies warrant determining the mechanism of PB in modulating replicative senescence of HDFs through these signaling pathways.

Piper betle L. Modulates Senescence-Associated Genes Expression in Replicative Senescent Human Diploid Fibroblasts.

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Durani, Lina Wati; Khor, Shy Cian; Tan, Jen Kit; Chua, Kien Hui; Mohd Yusof, Yasmin Anum; Makpol, Suzana

2017-01-01

Piper betle (PB) is a traditional medicine that is widely used to treat different diseases around Asian region. The leaf extracts contain various bioactive compounds, which were reported to have antidiabetic, antibacterial, anti-inflammatory, antioxidant, and anticancer effects. In this study, the effect of PB aqueous extracts on replicative senescent human diploid fibroblasts (HDFs) was investigated by determining the expressions of senescence-associated genes using quantitative PCR. Our results showed that PB extracts at 0.4 mg/ml can improve cell proliferation of young (143%), presenescent (127.3%), and senescent (157.3%) HDFs. Increased expressions of PRDX6 , TP53 , CDKN2A , PAK2 , and MAPK14 were observed in senescent HDFs compared to young and/or presenescent HDFs. Treatment with PB extracts modulates the transcriptional profile changes in senescent HDFs. By contrast, expressions of SOD1 increased, whereas GPX1 , PRDX6 , TP53 , CDKN2A , PAK2 , and MAPK14 were decreased in PB-treated senescent HDFs compared to untreated senescent HDFs. In conclusion, this study indicates the modulation of PB extracts on senescence-associated genes expression of replicative senescent HDFs. Further studies warrant determining the mechanism of PB in modulating replicative senescence of HDFs through these signaling pathways.

Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones.

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Devadas, Krishnakumar; Biswas, Santanu; Ragupathy, Viswanath; Lee, Sherwin; Dayton, Andrew; Hewlett, Indira

2018-01-01

Significant sex specific differences in the progression of HIV/AIDS have been reported. Several studies have implicated steroid hormones in regulating host factor expression and modulating HIV transmission and replication. However, the exact mechanism exerted by steroid hormones estrogen and progesterone in the regulation of HIV-1 replication is still unclear. Results from the current study indicated a dose dependent down regulation of HIV-1 replication in monocyte derived macrophages pre-treated with high concentrations of estrogen or progesterone. To elucidate the molecular mechanisms associated with the down regulation of HIV-1 replication by estrogen and progesterone we used PCR arrays to analyze the expression profile of host genes involved in antiviral responses. Several chemokines, cytokines, transcription factors, interferon stimulated genes and genes involved in type-1 interferon signaling were down regulated in cells infected with HIV-1 pre-treated with high concentrations of estrogen or progesterone compared to untreated HIV-1 infected cells or HIV-1 infected cells treated with low concentrations of estrogen or progesterone. The down regulation of CXCL9, CXCL10 and CXCL11 chemokines and IL-1β, IL-6 cytokines in response to high concentrations of estrogen and progesterone pre-treatment in HIV-1 infected cells was confirmed at the protein level by quantitating chemokine and cytokine concentrations in the culture supernatant. These results demonstrate that a potent anti-inflammatory response is mediated by pre-treatment with high concentrations of estrogen and progesterone. Thus, our study suggests a strong correlation between the down-modulation of anti-viral and pro-inflammatory responses mediated by estrogen and progesterone pre-treatment and the down regulation of HIV-1 replication. These findings may be relevant to clinical observations of sex specific differences in patient populations and point to the need for further investigation.

Optical transmission modules for multi-channel superconducting quantum interference device readouts

Energy Technology Data Exchange (ETDEWEB)

Kim, Jin-Mok, E-mail: jmkim@kriss.re.kr; Kwon, Hyukchan; Yu, Kwon-kyu; Lee, Yong-Ho; Kim, Kiwoong [Brain Cognition Measurement Center, Korea Research Institute of Standards and Science, Daejeon 305-600 (Korea, Republic of)

2013-12-15

We developed an optical transmission module consisting of 16-channel analog-to-digital converter (ADC), digital-noise filter, and one-line serial transmitter, which transferred Superconducting Quantum Interference Device (SQUID) readout data to a computer by a single optical cable. A 16-channel ADC sent out SQUID readouts data with 32-bit serial data of 8-bit channel and 24-bit voltage data at a sample rate of 1.5 kSample/s. A digital-noise filter suppressed digital noises generated by digital clocks to obtain SQUID modulation as large as possible. One-line serial transmitter reformed 32-bit serial data to the modulated data that contained data and clock, and sent them through a single optical cable. When the optical transmission modules were applied to 152-channel SQUID magnetoencephalography system, this system maintained a field noise level of 3 fT/√Hz @ 100 Hz.

Optical multiple-image hiding based on interference and grating modulation

International Nuclear Information System (INIS)

He, Wenqi; Peng, Xiang; Meng, Xiangfeng

2012-01-01

We present a method for multiple-image hiding on the basis of interference-based encryption architecture and grating modulation. By using a modified phase retrieval algorithm, we can separately hide a number of secret images into one arbitrarily preselected host image associated with a set of phase-only masks (POMs), which are regarded as secret keys. Thereafter, a grating modulation operation is introduced to multiplex and store the different POMs into a single key mask, which is then assigned to the authorized users in privacy. For recovery, after an appropriate demultiplexing process, one can reconstruct the distributions of all the secret keys and then recover the corresponding hidden images with suppressed crosstalk. Computer simulation results are presented to validate the feasibility of our approach. (paper)

SUMO and KSHV Replication

Energy Technology Data Exchange (ETDEWEB)

Chang, Pei-Ching [Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan (China); Kung, Hsing-Jien, E-mail: hkung@nhri.org.tw [Institute for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan (China); Department of Biochemistry and Molecular Medicine, University of California, Davis, CA 95616 (United States); UC Davis Cancer Center, University of California, Davis, CA 95616 (United States); Division of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan (China)

2014-09-29

Small Ubiquitin-related MOdifier (SUMO) modification was initially identified as a reversible post-translational modification that affects the regulation of diverse cellular processes, including signal transduction, protein trafficking, chromosome segregation, and DNA repair. Increasing evidence suggests that the SUMO system also plays an important role in regulating chromatin organization and transcription. It is thus not surprising that double-stranded DNA viruses, such as Kaposi’s sarcoma-associated herpesvirus (KSHV), have exploited SUMO modification as a means of modulating viral chromatin remodeling during the latent-lytic switch. In addition, SUMO regulation allows the disassembly and assembly of promyelocytic leukemia protein-nuclear bodies (PML-NBs), an intrinsic antiviral host defense, during the viral replication cycle. Overcoming PML-NB-mediated cellular intrinsic immunity is essential to allow the initial transcription and replication of the herpesvirus genome after de novo infection. As a consequence, KSHV has evolved a way as to produce multiple SUMO regulatory viral proteins to modulate the cellular SUMO environment in a dynamic way during its life cycle. Remarkably, KSHV encodes one gene product (K-bZIP) with SUMO-ligase activities and one gene product (K-Rta) that exhibits SUMO-targeting ubiquitin ligase (STUbL) activity. In addition, at least two viral products are sumoylated that have functional importance. Furthermore, sumoylation can be modulated by other viral gene products, such as the viral protein kinase Orf36. Interference with the sumoylation of specific viral targets represents a potential therapeutic strategy when treating KSHV, as well as other oncogenic herpesviruses. Here, we summarize the different ways KSHV exploits and manipulates the cellular SUMO system and explore the multi-faceted functions of SUMO during KSHV’s life cycle and pathogenesis.

DNA replication and cancer: From dysfunctional replication origin activities to therapeutic opportunities.

Science.gov (United States)

Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard

2016-06-01

A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways to promote genome integrity during DNA replication. This includes suppressing new replication origin firing, stabilization of replicating forks, and the safe restart of forks to prevent any loss of genetic information. Here, we describe mechanisms by which oncogenes can interfere with DNA replication thereby causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

The modulating effect of education on semantic interference during healthy aging.

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Daniela Paolieri

Full Text Available Aging has traditionally been related to impairments in name retrieval. These impairments have usually been explained by a phonological transmission deficit hypothesis or by an inhibitory deficit hypothesis. This decline can, however, be modulated by the educational level of the sample. This study analyzed the possible role of these approaches in explaining both object and face naming impairments during aging. Older adults with low and high educational level and young adults with high educational level were asked to repeatedly name objects or famous people using the semantic-blocking paradigm. We compared naming when exemplars were presented in a semantically homogeneous or in a semantically heterogeneous context. Results revealed significantly slower rates of both face and object naming in the homogeneous context (i.e., semantic interference, with a stronger effect for face naming. Interestingly, the group of older adults with a lower educational level showed an increased semantic interference effect during face naming. These findings suggest the joint work of the two mechanisms proposed to explain age-related naming difficulties, i.e., the inhibitory deficit and the transmission deficit hypothesis. Therefore, the stronger vulnerability to semantic interference in the lower educated older adult sample would possibly point to a failure in the inhibitory mechanisms in charge of interference resolution, as proposed by the inhibitory deficit hypothesis. In addition, the fact that this interference effect was mainly restricted to face naming and not to object naming would be consistent with the increased age-related difficulties during proper name retrieval, as suggested by the transmission deficit hypothesis.

The modulating effect of education on semantic interference during healthy aging.

Science.gov (United States)

Paolieri, Daniela; Marful, Alejandra; Morales, Luis; Bajo, María Teresa

2018-01-01

Aging has traditionally been related to impairments in name retrieval. These impairments have usually been explained by a phonological transmission deficit hypothesis or by an inhibitory deficit hypothesis. This decline can, however, be modulated by the educational level of the sample. This study analyzed the possible role of these approaches in explaining both object and face naming impairments during aging. Older adults with low and high educational level and young adults with high educational level were asked to repeatedly name objects or famous people using the semantic-blocking paradigm. We compared naming when exemplars were presented in a semantically homogeneous or in a semantically heterogeneous context. Results revealed significantly slower rates of both face and object naming in the homogeneous context (i.e., semantic interference), with a stronger effect for face naming. Interestingly, the group of older adults with a lower educational level showed an increased semantic interference effect during face naming. These findings suggest the joint work of the two mechanisms proposed to explain age-related naming difficulties, i.e., the inhibitory deficit and the transmission deficit hypothesis. Therefore, the stronger vulnerability to semantic interference in the lower educated older adult sample would possibly point to a failure in the inhibitory mechanisms in charge of interference resolution, as proposed by the inhibitory deficit hypothesis. In addition, the fact that this interference effect was mainly restricted to face naming and not to object naming would be consistent with the increased age-related difficulties during proper name retrieval, as suggested by the transmission deficit hypothesis.

Impact of Self-Interference on the Performance of Joint Partial RAKE Receiver and Adaptive Modulation

KAUST Repository

Nam, Sung Sik; Choi, Yungho; Alouini, Mohamed-Slim; Choi, Seyeong

2016-01-01

In this paper, we investigate the impact of self-interference on the performance of a joint partial RAKE (PRAKE) receiver and adaptive modulation over both independent and identically distributed and independent but non-identically distributed

Inhibition of influenza virus replication by targeting broad host cell pathways.

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Isabelle Marois

Full Text Available Antivirals that are currently used to treat influenza virus infections target components of the virus which can mutate rapidly. Consequently, there has been an increase in the number of resistant strains to one or many antivirals in recent years. Here we compared the antiviral effects of lysosomotropic alkalinizing agents (LAAs and calcium modulators (CMs, which interfere with crucial events in the influenza virus replication cycle, against avian, swine, and human viruses of different subtypes in MDCK cells. We observed that treatment with LAAs, CMs, or a combination of both, significantly inhibited viral replication. Moreover, the drugs were effective even when they were administered 8 h after infection. Finally, analysis of the expression of viral acidic polymerase (PA revealed that both drugs classes interfered with early events in the viral replication cycle. This study demonstrates that targeting broad host cellular pathways can be an efficient strategy to inhibit influenza replication. Furthermore, it provides an interesting avenue for drug development where resistance by the virus might be reduced since the virus is not targeted directly.

Modulation of Replicative Lifespan in Cryptococcus neoformans: Implications for Virulence

Science.gov (United States)

Bouklas, Tejas; Jain, Neena; Fries, Bettina C.

2017-01-01

The fungal pathogen, Cryptococcus neoformans, has been shown to undergo replicative aging. Old cells are characterized by advanced generational age and phenotypic changes that appear to mediate enhanced resistance to host and antifungal-based killing. As a consequence of this age-associated resilience, old cells accumulate during chronic infection. Based on these findings, we hypothesized that shifting the generational age of a pathogenic yeast population would alter its vulnerability to the host and affect its virulence. SIR2 is a well-conserved histone deacetylase, and a pivotal target for the development of anti-aging drugs. We tested its effect on C. neoformans’ replicative lifespan (RLS). First, a mutant C. neoformans strain (sir2Δ) was generated, and confirmed a predicted shortened RLS in sir2Δ cells consistent with its known role in aging. Next, RLS analysis showed that treatment of C. neoformans with Sir2p-agonists resulted in a significantly prolonged RLS, whereas treatment with a Sir2p-antagonist shortened RLS. RLS modulating effects were dependent on SIR2 and not observed in sir2Δ cells. Because SIR2 loss resulted in a slightly impaired fitness, effects of genetic RLS modulation on virulence could not be compared with wild type cells. Instead we chose to chemically modulate RLS, and investigated the effect of Sir2p modulating drugs on C. neoformans cells in a Galleria mellonella infection model. Consistent with our hypothesis that shifts in the generational age of the infecting yeast population alters its vulnerability to host cells, we observed decreased virulence of C. neoformans in the Galleria host when RLS was prolonged by treatment with Sir2p agonists. In contrast, treatment with a Sir2p antagonist, which shortens RLS enhanced virulence in Galleria. In addition, combination of Sir2p agonists with antifungal therapy enhanced the antifungal’s effect. Importantly, no difference in virulence was observed with drug treatment when sir2Δ cells

Inhibition of virus replication by RNA interference

NARCIS (Netherlands)

Haasnoot, P. C. Joost; Cupac, Daniel; Berkhout, Ben

2003-01-01

RNA interference (RNAi) is a sequence-specific gene-silencing mechanism in eukaryotes, which is believed to function as a defence against viruses and transposons. Since its discovery, RNAi has been developed into a widely used technique for generating genetic knock-outs and for studying gene

Viral Interference and Persistence in Mosquito-Borne Flaviviruses

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Juan Santiago Salas-Benito

2015-01-01

Full Text Available Mosquito-borne flaviviruses are important pathogens for humans, and the detection of two or more flaviviruses cocirculating in the same geographic area has often been reported. However, the epidemiological impact remains to be determined. Mosquito-borne flaviviruses are primarily transmitted through Aedes and Culex mosquitoes; these viruses establish a life-long or persistent infection without apparent pathological effects. This establishment requires a balance between virus replication and the antiviral host response. Viral interference is a phenomenon whereby one virus inhibits the replication of other viruses, and this condition is frequently associated with persistent infections. Viral interference and persistent infection are determined by several factors, such as defective interfering particles, competition for cellular factors required for translation/replication, and the host antiviral response. The interaction between two flaviviruses typically results in viral interference, indicating that these viruses share common features during the replicative cycle in the vector. The potential mechanisms involved in these processes are reviewed here.

Exploiting Genetic Interference for Antiviral Therapy.

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Elizabeth J Tanner

2016-05-01

Full Text Available Rapidly evolving viruses are a major threat to human health. Such viruses are often highly pathogenic (e.g., influenza virus, HIV, Ebola virus and routinely circumvent therapeutic intervention through mutational escape. Error-prone genome replication generates heterogeneous viral populations that rapidly adapt to new selection pressures, leading to resistance that emerges with treatment. However, population heterogeneity bears a cost: when multiple viral variants replicate within a cell, they can potentially interfere with each other, lowering viral fitness. This genetic interference can be exploited for antiviral strategies, either by taking advantage of a virus's inherent genetic diversity or through generating de novo interference by engineering a competing genome. Here, we discuss two such antiviral strategies, dominant drug targeting and therapeutic interfering particles. Both strategies harness the power of genetic interference to surmount two particularly vexing obstacles-the evolution of drug resistance and targeting therapy to high-risk populations-both of which impede treatment in resource-poor settings.

Study the effects of varying interference upon the optical properties of turbid samples using NIR spatial light modulation

Science.gov (United States)

Shaul, Oren; Fanrazi-Kahana, Michal; Meitav, Omri; Pinhasi, Gad A.; Abookasis, David

2018-03-01

Optical properties of biological tissues are valuable diagnostic parameters which can provide necessary information regarding tissue state during disease pathogenesis and therapy. However, different sources of interference, such as temperature changes may modify these properties, introducing confounding factors and artifacts to data, consequently skewing their interpretation and misinforming clinical decision-making. In the current study, we apply spatial light modulation, a type of diffuse reflectance hyperspectral imaging technique, to monitor the variation in optical properties of highly scattering turbid media in the presence varying levels of the following sources of interference: scattering concentration, temperature, and pressure. Spatial near-infrared (NIR) light modulation is a wide-field, non-contact emerging optical imaging platform capable of separating the effects of tissue scattering from those of absorption, thereby accurately estimating both parameters. With this technique, periodic NIR illumination patterns at alternately low and high spatial frequencies, at six discrete wavelengths between 690 to 970 nm, were sequentially projected upon the medium while a CCD camera collects the diffusely reflected light. Data analysis based assumptions is then performed off-line to recover the medium's optical properties. We conducted a series of experiments demonstrating the changes in absorption and reduced scattering coefficients of commercially available fresh milk and chicken breast tissue under different interference conditions. In addition, information on the refractive index was study under increased pressure. This work demonstrates the utility of NIR spatial light modulation to detect varying sources of interference upon the optical properties of biological samples.

Wafer defect detection by a polarization-insensitive external differential interference contrast module.

Science.gov (United States)

Nativ, Amit; Feldman, Haim; Shaked, Natan T

2018-05-01

We present a system that is based on a new external, polarization-insensitive differential interference contrast (DIC) module specifically adapted for detecting defects in semiconductor wafers. We obtained defect signal enhancement relative to the surrounding wafer pattern when compared with bright-field imaging. The new DIC module proposed is based on a shearing interferometer that connects externally at the output port of an optical microscope and enables imaging thin samples, such as wafer defects. This module does not require polarization optics (such as Wollaston or Nomarski prisms) and is insensitive to polarization, unlike traditional DIC techniques. In addition, it provides full control of the DIC shear and orientation, which allows obtaining a differential phase image directly on the camera (with no further digital processing) while enhancing defect detection capabilities, even if the size of the defect is smaller than the resolution limit. Our technique has the potential of future integration into semiconductor production lines.

Extremal dynamics in random replicator ecosystems

Energy Technology Data Exchange (ETDEWEB)

Kärenlampi, Petri P., E-mail: petri.karenlampi@uef.fi

2015-10-02

The seminal numerical experiment by Bak and Sneppen (BS) is repeated, along with computations with replicator models, including a greater amount of features. Both types of models do self-organize, and do obey power-law scaling for the size distribution of activity cycles. However species extinction within the replicator models interferes with the BS self-organized critical (SOC) activity. Speciation–extinction dynamics ruins any stationary state which might contain a steady size distribution of activity cycles. The BS-type activity appears as a dissimilar phenomenon in comparison to speciation–extinction dynamics in the replicator system. No criticality is found from the speciation–extinction dynamics. Neither are speciations and extinctions in real biological macroevolution known to contain any diverging distributions, or self-organization towards any critical state. Consequently, biological macroevolution probably is not a self-organized critical phenomenon. - Highlights: • Extremal Dynamics organizes random replicator ecosystems to two phases in fitness space. • Replicator systems show power-law scaling of activity. • Species extinction interferes with Bak–Sneppen type mutation activity. • Speciation–extinction dynamics does not show any critical phase transition. • Biological macroevolution probably is not a self-organized critical phenomenon.

Does an attention bias to appetitive and aversive words modulate interference control in youth with ADHD?

Science.gov (United States)

Ma, Ili; Mies, Gabry W; Lambregts-Rommelse, Nanda N J; Buitelaar, Jan K; Cillessen, Antonius H N; Scheres, Anouk

2018-05-01

Interference control refers to the ability to selectively attend to certain information while ignoring distracting information. This ability can vary as a function of distractor relevance. Distractors that are particularly relevant to an individual may attract more attention than less relevant distractors. This is referred to as attention bias. Weak interference control and altered reward sensitivity are both important features of attention deficit hyperactivity disorder (ADHD). However, interference control is typically studied in isolation. This study integrates both. Youths (aged 9 to 17 years) with ADHD (n = 37, 25 boys) and typically-developing controls (n = 38, 20 boys) completed a Stroop task using appetitive words and matched neutral words to assess whether appetitive distractors diminished interference control more in youths with ADHD than controls. In order to test for specificity, aversive words were also included. As expected, appetitive words disrupted interference control but this effect was not stronger for youths with ADHD than the controls. Aversive words, on the other hand, facilitated interference control. Dimensional analyses revealed that this facilitation effect increased substantially as a function of ADHD symptom severity. Possible mechanisms for this effect include up-regulation of interference control as a function of induced negative mood, or as a function of increased effort. In conclusion, appetitive words do not lead to worse interference control in youths with ADHD compared with controls. Interference control was modulated in a valence-specific manner, concurrent with mood-induced effects on cognitive control.

Using Interference to Block RFID Tags

DEFF Research Database (Denmark)

Krigslund, Rasmus; Popovski, Petar; Pedersen, Gert Frølund

We propose a novel method to block RFID tags from responding, using intentional interference. We focus on the experimental evaluation, where we impose interference on the download and uplink, respectively. The results are positive, where modulated CCI shows most effective to block a tag.......We propose a novel method to block RFID tags from responding, using intentional interference. We focus on the experimental evaluation, where we impose interference on the download and uplink, respectively. The results are positive, where modulated CCI shows most effective to block a tag....

Stop feeling: inhibition of emotional interference following stop-signal trials.

Science.gov (United States)

Kalanthroff, Eyal; Cohen, Noga; Henik, Avishai

2013-01-01

Although a great deal of literature has been dedicated to the mutual links between emotion and the selective attention component of executive control, there is very little data regarding the links between emotion and the inhibitory component of executive control. In the current study we employed an emotional stop-signal task in order to examine whether emotion modulates and is modulated by inhibitory control. Results replicated previous findings showing reduced inhibitory control [longer stop-signal reaction time (SSRT)] following negative, compared to neutral pictures. Most importantly, results show decreased emotional interference following stop-signal trials. These results show that the inhibitory control component of executive control can serve to decrease emotional effects. We suggest that inhibitory control and emotion have a two-way connection in which emotion disrupts inhibitory control and activation of inhibitory control disrupts emotion.

Stop feeling: Inhibition of emotional interference following stop-signal trials

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Eyal eKalanthroff

2013-03-01

Full Text Available Although a great deal of literature has been dedicated to the mutual links between emotion and the selective attention component of executive control, there is very little data regarding the links between emotion and the inhibitory component of executive control. In the current study we employed an emotional stop-signal task in order to examine whether emotion modulates and is modulated by inhibitory control. Results replicated previous findings showing reduced inhibitory control (longer stop-signal reaction time following negative, compared to neutral pictures. Most importantly, results show decreased emotional interference following stop-signal trials. These results show that the inhibitory control component of executive control can serve to decrease emotional effects. We suggest that inhibitory control and emotion have a two-way connection in which emotion disrupts inhibitory control and activation of inhibitory control disrupts emotion.

Unravelling the role of quantum interference in the weak-field laser phase modulation control of photofragment distributions

DEFF Research Database (Denmark)

García-Vela, Alberto; Henriksen, Niels Engholm

2016-01-01

The role played by quantum interference in the laser phase modulation coherent control of photofragment distributions in the weak-field regime is investigated in detail in this work. The specific application involves realistic wave packet calculations of the transient vibrational populations of t...

Structure modulates similarity-based interference in sluicing: An eye tracking study.

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Jesse A. Harris

2015-12-01

Full Text Available In cue-based content-addressable approaches to memory, a target and its competitors are retrieved in parallel from memory via a fast, associative cue-matching procedure under a severely limited focus of attention. Such a parallel matching procedure could in principle ignore the serial order or hierarchical structure characteristic of linguistic relations. I present an eye tracking while reading experiment that investigates whether the sentential position of a potential antecedent modulates the strength of similarity-based interference, a well-studied effect in which increased similarity in features between a target and its competitors results in slower and less accurate retrieval overall. The manipulation trades on an independently established Locality bias in sluiced structures to associate a wh-remnant (which ones in clausal ellipsis with the most local correlate (some wines, as in The tourists enjoyed some wines, but I don’t know which ones. The findings generally support cue-based parsing models of sentence processing that are subject to similarity-based interference in retrieval, and provide additional support to the growing body of evidence that retrieval is sensitive to both the structural position of a target antecedent and its competitors, and the specificity of retrieval cues.

Astrocyte Apoptosis and HIV Replication Are Modulated in Host Cells Coinfected with Trypanosoma cruzi

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Javier M. Urquiza

2017-08-01

Full Text Available The protozoan Trypanosoma cruzi is the etiological agent of Chagas disease. In immunosuppressed individuals, as it occurs in the coinfection with human immunodeficiency virus (HIV, the central nervous system may be affected. In this regard, reactivation of Chagas disease is severe and often lethal, and it accounts for meningoencephalitis. Astrocytes play a crucial role in the environment maintenance of healthy neurons; however, they can host HIV and T. cruzi. In this report, human astrocytes were infected in vitro with both genetically modified-pathogens to express alternative fluorophore. As evidenced by fluorescence microscopy and flow cytometry, HIV and T. cruzi coexist in the same astrocyte, likely favoring reciprocal interactions. In this context, lower rates of cell death were observed in both T. cruzi monoinfected-astrocytes and HIV-T. cruzi coinfection in comparison with those infected only with HIV. The level of HIV replication is significantly diminished under T. cruzi coinfection, but without affecting the infectivity of the HIV progeny. This interference with viral replication appears to be related to the T. cruzi multiplication rate or its increased intracellular presence but does not require their intracellular cohabitation or infected cell-to-cell contact. Among several Th1/Th2/Th17 profile-related cytokines, only IL-6 was overexpressed in HIV-T. cruzi coinfection exhibiting its cytoprotective role. This study demonstrates that T. cruzi and HIV are able to coinfect astrocytes thus altering viral replication and apoptosis.

Modulating effect of COMT Val(158)Met polymorphism on interference resolution during a working memory task.

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Jaspar, Mathieu; Dideberg, Vinciane; Bours, Vincent; Maquet, Pierre; Collette, Fabienne

2015-04-01

Genetic variability related to the catechol-O-methyltransferase (COMT) gene has received increasing attention in the last 15years, in particular as a potential modulator of the neural substrates underlying inhibitory processes and updating in working memory (WM). In an event-related functional magnetic resonance imaging (fMRI) study, we administered a modified version of the Sternberg probe recency task (Sternberg, 1966) to 43 young healthy volunteers, varying the level of interference across successive items. The task was divided into two parts (high vs. low interference) to induce either proactive or reactive control processes. The participants were separated into three groups according to their COMT Val(158)Met genotype [Val/Val (VV); Val/Met (VM); Met/Met (MM)]. The general aim of the study was to determine whether COMT polymorphism has a modulating effect on the neural substrates of interference resolution during WM processing. Results indicate that interfering trials were associated with greater involvement of frontal cortices (bilateral medial frontal gyrus, left precentral and superior frontal gyri, right inferior frontal gyrus) in VV homozygous subjects (by comparison to Met allele carriers) only in the proactive condition of the task. In addition, analysis of peristimulus haemodynamic responses (PSTH) revealed that the genotype-related difference observed in the left SFG was specifically driven by a larger increase in activity from the storage to the recognition phase of the interfering trials in VV homozygous subjects. These results confirm the impact of COMT genotype on inhibitory processes during a WM task, with an advantage for Met allele carriers. Interestingly, this impact on frontal areas is present only when the level of interference is high, and especially during the transition from storage to recognition in the left superior frontal gyrus. Copyright © 2015 Elsevier Inc. All rights reserved.

Replication stress interferes with histone recycling and predeposition marking of new histones

DEFF Research Database (Denmark)

Jasencakova, Zuzana; Scharf, Annette N D; Ask, Katrine

2010-01-01

To restore chromatin on new DNA during replication, recycling of histones evicted ahead of the fork is combined with new histone deposition. The Asf1 histone chaperone, which buffers excess histones under stress, is a key player in this process. Yet how histones handled by human Asf1 are modified...... remains unclear. Here we identify marks on histones H3-H4 bound to Asf1 and changes induced upon replication stress. In S phase, distinct cytosolic and nuclear Asf1b complexes show ubiquitous H4K5K12diAc and heterogeneous H3 marks, including K9me1, K14ac, K18ac, and K56ac. Upon acute replication arrest......, the predeposition mark H3K9me1 and modifications typical of chromatin accumulate in Asf1 complexes. In parallel, ssDNA is generated at replication sites, consistent with evicted histones being trapped with Asf1. During recovery, histones stored with Asf1 are rapidly used as replication resumes. This shows...

DNA polymerase η modulates replication fork progression and DNA damage responses in platinum-treated human cells

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Sokol, Anna M.; Cruet-Hennequart, Séverine; Pasero, Philippe; Carty, Michael P.

2013-11-01

Human cells lacking DNA polymerase η (polη) are sensitive to platinum-based cancer chemotherapeutic agents. Using DNA combing to directly investigate the role of polη in bypass of platinum-induced DNA lesions in vivo, we demonstrate that nascent DNA strands are up to 39% shorter in human cells lacking polη than in cells expressing polη. This provides the first direct evidence that polη modulates replication fork progression in vivo following cisplatin and carboplatin treatment. Severe replication inhibition in individual platinum-treated polη-deficient cells correlates with enhanced phosphorylation of the RPA2 subunit of replication protein A on serines 4 and 8, as determined using EdU labelling and immunofluorescence, consistent with formation of DNA strand breaks at arrested forks in the absence of polη. Polη-mediated bypass of platinum-induced DNA lesions may therefore represent one mechanism by which cancer cells can tolerate platinum-based chemotherapy.

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy.

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Allan, Kristina J; Mahoney, Douglas J; Baird, Stephen D; Lefebvre, Charles A; Stojdl, David F

2018-04-03

High-throughput genome-wide RNAi (RNA interference) screening technology has been widely used for discovering host factors that impact virus replication. Here we present the application of this technology to uncovering host targets that specifically modulate the replication of Maraba virus, an oncolytic rhabdovirus, and vaccinia virus with the goal of enhancing therapy. While the protocol has been tested for use with oncolytic Maraba virus and oncolytic vaccinia virus, this approach is applicable to other oncolytic viruses and can also be utilized for identifying host targets that modulate virus replication in mammalian cells in general. This protocol describes the development and validation of an assay for high-throughput RNAi screening in mammalian cells, the key considerations and preparation steps important for conducting a primary high-throughput RNAi screen, and a step-by-step guide for conducting a primary high-throughput RNAi screen; in addition, it broadly outlines the methods for conducting secondary screen validation and tertiary validation studies. The benefit of high-throughput RNAi screening is that it allows one to catalogue, in an extensive and unbiased fashion, host factors that modulate any aspect of virus replication for which one can develop an in vitro assay such as infectivity, burst size, and cytotoxicity. It has the power to uncover biotherapeutic targets unforeseen based on current knowledge.

Transcranial cavitation-mediated ultrasound therapy at sub-MHz frequency via temporal interference modulation

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Sun, Tao; Sutton, Jonathan T.; Power, Chanikarn; Zhang, Yongzhi; Miller, Eric L.; McDannold, Nathan J.

2017-10-01

Sub-megahertz transmission is not usually adopted in pre-clinical small animal experiments for focused ultrasound (FUS) brain therapy due to the large focal size. However, low frequency FUS is vital for preclinical evaluations due to the frequency-dependence of cavitation behavior. To maximize clinical relevance, a dual-aperture FUS system was designed for low-frequency (274.3 kHz) cavitation-mediated FUS therapy. Combining two spherically curved transducers provides significantly improved focusing in the axial direction while yielding an interference pattern with strong side lobes, leading to inhomogeneously distributed cavitation activities. By operating the two transducers at slightly offset frequencies to modulate this interference pattern over the period of sonication, the acoustic energy was redistributed and resulted in a spatially homogenous treatment profile. Simulation and pressure field measurements in water were performed to assess the beam profiles. In addition, the system performance was demonstrated in vivo in rats via drug delivery through microbubble-mediated blood-brain barrier disruption. This design resulted in a homogenous treatment profile that was fully contained within the rat brain at a clinically relevant acoustic frequency.

p53 Maintains Genomic Stability by Preventing Interference between Transcription and Replication

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Constance Qiao Xin Yeo

2016-04-01

Full Text Available p53 tumor suppressor maintains genomic stability, typically acting through cell-cycle arrest, senescence, and apoptosis. We discovered a function of p53 in preventing conflicts between transcription and replication, independent of its canonical roles. p53 deficiency sensitizes cells to Topoisomerase (Topo II inhibitors, resulting in DNA damage arising spontaneously during replication. Topoisomerase IIα (TOP2A-DNA complexes preferentially accumulate in isogenic p53 mutant or knockout cells, reflecting an increased recruitment of TOP2A to regulate DNA topology. We propose that p53 acts to prevent DNA topological stress originating from transcription during the S phase and, therefore, promotes normal replication fork progression. Consequently, replication fork progression is impaired in the absence of p53, which is reversed by transcription inhibition. Pharmacologic inhibition of transcription also attenuates DNA damage and decreases Topo-II-DNA complexes, restoring cell viability in p53-deficient cells. Together, our results demonstrate a function of p53 that may underlie its role in tumor suppression.

Performance analysis of an optical self-interference cancellation system with a directly modulated laser-based demonstration.

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Yu, Yinghong; Zhang, Yunhao; Huang, Lin; Xiao, Shilin

2018-02-20

In this paper, two main performance indices of the optical self-interference cancellation (OSIC) system are theoretically analyzed: cancellation bandwidth and depth. Delay deviation is investigated to be the determining factor of cancellation bandwidth, based on which the bandwidth advantage of the OSIC system over electrical schemes is also proven theoretically. Cancellation depth in the narrowband is mostly influenced by attenuation and delay-adjusting deviation, while in the broadband case, the performance is mostly limited by frequency-dependent amplitude and phase mismatch. The cancellation performance analysis is suitable for most linear modulation-demodulation OSIC systems, including the directly modulated laser (DML)-based OSIC system verified experimentally in this paper. The cancellation model is well demonstrated by the agreement between experimental cancellation results and predicted performance. For over-the-air demonstration with the employment of antennas, broadband cancellation within 450 MHz bandwidth of 22 dB and 25 dB is achieved at 900 MHz and 2.4 GHz, respectively. In addition, orthogonal frequency division multiplexing signals are employed to show in-band full-duplex transmission with good performance by the DML-based OSIC system, with successful suppression of self-interference and recovery of the signal of interest.

Inhibition of influenza A virus replication by influenza B virus nucleoprotein: An insight into interference between influenza A and B viruses

Energy Technology Data Exchange (ETDEWEB)

Wanitchang, Asawin; Narkpuk, Jaraspim; Jaru-ampornpan, Peera; Jengarn, Juggagarn [Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathumthani 12120 (Thailand); Jongkaewwattana, Anan, E-mail: anan.jon@biotec.or.th [Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathumthani 12120 (Thailand)

2012-10-10

Given that co-infection of cells with equivalent titers of influenza A and B viruses (FluA and FluB) has been shown to result in suppression of FluA growth, it is possible that FluB-specific proteins might hinder FluA polymerase activity and replication. We addressed this possibility by individually determining the effect of each gene of FluB on the FluA polymerase assay and found that the nucleoprotein of FluB (NP{sub FluB}) inhibits polymerase activity of FluA in a dose-dependent manner. Mutational analyses of NP{sub FluB} suggest that functional NP{sub FluB} is necessary for this inhibition. Slower growth of FluA was also observed in MDCK cells stably expressing NP{sub FluB}. Further analysis of NP{sub FluB} indicated that it does not affect nuclear import of NP{sub FluA}. Taken together, these findings suggest a novel role of NP{sub FluB} in inhibiting replication of FluA, providing more insights into the mechanism of interference between FluA and FluB and the lack of reassortants between them.

CRISPR/Cas9-Mediated Immunity to Geminiviruses: Differential Interference and Evasion

KAUST Repository

Ali, Zahir; Ali, Shawkat; Tashkandi, Manal; Zaidi, Syed Shan-e-Ali; Mahfouz, Magdy M.

2016-01-01

The CRISPR/Cas9 system has recently been used to confer molecular immunity against several eukaryotic viruses, including plant DNA geminiviruses. Here, we provide a detailed analysis of the efficiencies of targeting different coding and non-coding sequences in the genomes of multiple geminiviruses. Moreover, we analyze the ability of geminiviruses to evade the CRISPR/Cas9 machinery. Our results demonstrate that the CRISPR/Cas9 machinery can efficiently target coding and non-coding sequences and interfere with various geminiviruses. Furthermore, targeting the coding sequences of different geminiviruses resulted in the generation of viral variants capable of replication and systemic movement. By contrast, targeting the noncoding intergenic region sequences of geminiviruses resulted in interference, but with inefficient recovery of mutated viral variants, which thus limited the generation of variants capable of replication and movement. Taken together, our results indicate that targeting noncoding, intergenic sequences provides viral interference activity and significantly limits the generation of viral variants capable of replication and systemic infection, which is essential for developing durable resistance strategies for long-term virus control.

CRISPR/Cas9-Mediated Immunity to Geminiviruses: Differential Interference and Evasion

KAUST Repository

Ali, Zahir

2016-05-26

The CRISPR/Cas9 system has recently been used to confer molecular immunity against several eukaryotic viruses, including plant DNA geminiviruses. Here, we provide a detailed analysis of the efficiencies of targeting different coding and non-coding sequences in the genomes of multiple geminiviruses. Moreover, we analyze the ability of geminiviruses to evade the CRISPR/Cas9 machinery. Our results demonstrate that the CRISPR/Cas9 machinery can efficiently target coding and non-coding sequences and interfere with various geminiviruses. Furthermore, targeting the coding sequences of different geminiviruses resulted in the generation of viral variants capable of replication and systemic movement. By contrast, targeting the noncoding intergenic region sequences of geminiviruses resulted in interference, but with inefficient recovery of mutated viral variants, which thus limited the generation of variants capable of replication and movement. Taken together, our results indicate that targeting noncoding, intergenic sequences provides viral interference activity and significantly limits the generation of viral variants capable of replication and systemic infection, which is essential for developing durable resistance strategies for long-term virus control.

Chromatin Controls DNA Replication Origin Selection, Lagging-Strand Synthesis, and Replication Fork Rates.

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Kurat, Christoph F; Yeeles, Joseph T P; Patel, Harshil; Early, Anne; Diffley, John F X

2017-01-05

The integrity of eukaryotic genomes requires rapid and regulated chromatin replication. How this is accomplished is still poorly understood. Using purified yeast replication proteins and fully chromatinized templates, we have reconstituted this process in vitro. We show that chromatin enforces DNA replication origin specificity by preventing non-specific MCM helicase loading. Helicase activation occurs efficiently in the context of chromatin, but subsequent replisome progression requires the histone chaperone FACT (facilitates chromatin transcription). The FACT-associated Nhp6 protein, the nucleosome remodelers INO80 or ISW1A, and the lysine acetyltransferases Gcn5 and Esa1 each contribute separately to maximum DNA synthesis rates. Chromatin promotes the regular priming of lagging-strand DNA synthesis by facilitating DNA polymerase α function at replication forks. Finally, nucleosomes disrupted during replication are efficiently re-assembled into regular arrays on nascent DNA. Our work defines the minimum requirements for chromatin replication in vitro and shows how multiple chromatin factors might modulate replication fork rates in vivo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Neural correlates of interference resolution in the multi-source interference task: a meta-analysis of functional neuroimaging studies.

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Deng, Yuqin; Wang, Xiaochun; Wang, Yan; Zhou, Chenglin

2018-04-10

Interference resolution refers to cognitive control processes enabling one to focus on task-related information while filtering out unrelated information. But the exact neural areas, which underlie a specific cognitive task on interference resolution, are still equivocal. The multi-source interference task (MSIT), as a particular cognitive task, is a well-established experimental paradigm used to evaluate interference resolution. Studies combining the MSIT with functional magnetic resonance imaging (fMRI) have shown that the MSIT evokes the dorsal anterior cingulate cortex (dACC) and cingulate-frontal-parietal cognitive-attentional networks. However, these brain areas have not been evaluated quantitatively and these findings have not been replicated. In the current study, we firstly report a voxel-based meta-analysis of functional brain activation associated with the MSIT so as to identify the localization of interference resolution in such a specific cognitive task. Articles on MSIT-related fMRI published between 2003 and July 2017 were eligible. The electronic databases searched included PubMed, Web of Knowledge, and Google Scholar. Differential BOLD activation patterns between the incongruent and congruent condition were meta-analyzed in anisotropic effect-size signed differential mapping software. Robustness meta-analysis indicated that two significant activation clusters were shown to have reliable functional activity in comparisons between incongruent and congruent conditions. The first reliable activation cluster, which included the dACC, medial prefrontal cortex, supplementary motor area, replicated the previous MSIT-related fMRI study results. Furthermore, we found another reliable activation cluster comprising areas of the right insula, right inferior frontal gyrus, and right lenticular nucleus-putamen, which were not typically discussed in previous MSIT-related fMRI studies. The current meta-analysis study presents the reliable brain activation patterns

Viral hijacking of a replicative helicase loader and its implications for helicase loading control and phage replication

Energy Technology Data Exchange (ETDEWEB)

Hood, Iris V.; Berger, James M.

2016-05-31

Replisome assembly requires the loading of replicative hexameric helicases onto origins by AAA+ ATPases. How loader activity is appropriately controlled remains unclear. Here, we use structural and biochemical analyses to establish how an antimicrobial phage protein interferes with the function of theStaphylococcus aureusreplicative helicase loader, DnaI. The viral protein binds to the loader’s AAA+ ATPase domain, allowing binding of the host replicative helicase but impeding loader self-assembly and ATPase activity. Close inspection of the complex highlights an unexpected locus for the binding of an interdomain linker element in DnaI/DnaC-family proteins. We find that the inhibitor protein is genetically coupled to a phage-encoded homolog of the bacterial helicase loader, which we show binds to the host helicase but not to the inhibitor itself. These findings establish a new approach by which viruses can hijack host replication processes and explain how loader activity is internally regulated to prevent aberrant auto-association.

Initiation at closely spaced replication origins in a yeast chromosome.

Science.gov (United States)

Brewer, B J; Fangman, W L

1993-12-10

Replication of eukaryotic chromosomes involves initiation at origins spaced an average of 50 to 100 kilobase pairs. In yeast, potential origins can be recognized as autonomous replication sequences (ARSs) that allow maintenance of plasmids. However, there are more ARS elements than active chromosomal origins. The possibility was examined that close spacing of ARSs can lead to inactive origins. Two ARSs located 6.5 kilobase pairs apart can indeed interfere with each other. Replication is initiated from one or the other ARS with equal probability, but rarely (< 5%) from both ARSs on the same DNA molecule.

Identification of a New Ribonucleoside Inhibitor of Ebola Virus Replication

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Olivier Reynard

2015-12-01

Full Text Available The current outbreak of Ebola virus (EBOV in West Africa has claimed the lives of more than 15,000 people and highlights an urgent need for therapeutics capable of preventing virus replication. In this study we screened known nucleoside analogues for their ability to interfere with EBOV replication. Among them, the cytidine analogue β-d-N4-hydroxycytidine (NHC demonstrated potent inhibitory activities against EBOV replication and spread at non-cytotoxic concentrations. Thus, NHC constitutes an interesting candidate for the development of a suitable drug treatment against EBOV.

Identification and characterization of the host protein DNAJC14 as a broadly active flavivirus replication modulator.

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Zhigang Yi

2011-01-01

Full Text Available Viruses in the Flavivirus genus of the Flaviviridae family are arthropod-transmitted and contribute to staggering numbers of human infections and significant deaths annually across the globe. To identify cellular factors with antiviral activity against flaviviruses, we screened a cDNA library using an iterative approach. We identified a mammalian Hsp40 chaperone protein (DNAJC14 that when overexpressed was able to mediate protection from yellow fever virus (YFV-induced cell death. Further studies revealed that DNAJC14 inhibits YFV at the step of viral RNA replication. Since replication of bovine viral diarrhea virus (BVDV, a member of the related Pestivirus genus, is also known to be modulated by DNAJC14, we tested the effect of this host factor on diverse Flaviviridae family members. Flaviviruses, including the pathogenic Asibi strain of YFV, Kunjin, and tick-borne Langat virus, as well as a Hepacivirus, hepatitis C virus (HCV, all were inhibited by overexpression of DNAJC14. Mutagenesis showed that both the J-domain and the C-terminal domain, which mediates self-interaction, are required for anti-YFV activity. We found that DNAJC14 does not block YFV nor HCV NS2-3 cleavage, and using non-inhibitory mutants demonstrate that DNAJC14 is recruited to YFV replication complexes. Immunofluorescence analysis demonstrated that endogenous DNAJC14 rearranges during infection and is found in replication complexes identified by dsRNA staining. Interestingly, silencing of endogenous DNAJC14 results in impaired YFV replication suggesting a requirement for DNAJC14 in YFV replication complex assembly. Finally, the antiviral activity of overexpressed DNAJC14 occurs in a time- and dose-dependent manner. DNAJC14 overexpression may disrupt the proper stoichiometry resulting in inhibition, which can be overcome upon restoration of the optimal ratios due to the accumulation of viral nonstructural proteins. Our findings, together with previously published work

The Escherichia coli Tus-Ter replication fork barrier causes site-specific DNA replication perturbation in yeast.

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Larsen, Nicolai B; Sass, Ehud; Suski, Catherine; Mankouri, Hocine W; Hickson, Ian D

2014-04-07

Replication fork (RF) pausing occurs at both 'programmed' sites and non-physiological barriers (for example, DNA adducts). Programmed RF pausing is required for site-specific DNA replication termination in Escherichia coli, and this process requires the binding of the polar terminator protein, Tus, to specific DNA sequences called Ter. Here, we demonstrate that Tus-Ter modules also induce polar RF pausing when engineered into the Saccharomyces cerevisiae genome. This heterologous RF barrier is distinct from a number of previously characterized, protein-mediated, RF pause sites in yeast, as it is neither Tof1-dependent nor counteracted by the Rrm3 helicase. Although the yeast replisome can overcome RF pausing at Tus-Ter modules, this event triggers site-specific homologous recombination that requires the RecQ helicase, Sgs1, for its timely resolution. We propose that Tus-Ter can be utilized as a versatile, site-specific, heterologous DNA replication-perturbing system, with a variety of potential applications.

Application of chaotic pulse width modulation control for suppressing electromagnetic interference in a half-bridge converter

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Yuhong Song

2014-08-01

Full Text Available It was proposed in the former research that chaos control can be used to suppress electromagnetic interference (EMI in DC–DC converters. Analysis on a half-bridge converter is detailed in this study. Here, the practical example of the power supply of personal computers is given to show that, with an external chaotic signal to a pulse width modulation control circuit, the proposed approach can reduce EMI by reducing the amplitudes of power signals such as transformer current and output inductor currents at multiples of fundamental frequency.

FAGE measurements of tropospheric HO with measurements and model of interferences

Science.gov (United States)

Hard, T. M.; Mehrabzadeh, A. A.; Chan, C. Y.; O'Brien, R. J.

1992-01-01

Ambient HO measurements by low-pressure laser-excited fluorescence with chemical modulation, and supporting ozone and water-vapor data, are presented for periods in May and August 1987. The observed peak daytime ambient HO concentrations are in the range (2.5 to 8) x 10 exp 6 molecules/cu cm and show small negative offsets due to photochemical interference. Direct measurements of the interference at fixed (O3) give the dependence on ambient (H2O) and on the modulating reagent (isobutane). At ambient (O3) = 30 ppb and 10 torr H2O, with excitation and detection at a total pressure of 4 torr, the net interference is equal to (HO) = -1.3 x 10 exp 6 molecules/cu cm. Production of HO by the reaction of isobutane with O(1D) accounts for the negative interference. Quenching of HO fluorescence by the modulating reagent contributes a smaller positive term to the interference; kinetic measurements of the quenching rate coefficient are reported. The experimental interference results are compared with a detailed kinetic model of HO production, excitation, relaxation, and detection; reasonable agreement is found.

MCM interference during licensing of DNA replication in Xenopus egg extracts-Possible Role of a C-terminal region of MCM3.

Science.gov (United States)

Mimura, Satoru; Kubota, Yumiko; Takisawa, Haruhiko

2018-01-01

The minichromosome maintenance (MCM) complex, consisting of six subunits, Mcm2-7, is loaded onto replication origins through loading factors (origin recognition complex [ORC], Cdc6, and Cdt1) and forms an MCM double hexamer that licenses the initiation of DNA replication. Previous studies with Xenopus egg extracts showed that loading factors, especially Cdc6, dissociate from chromatin on MCM loading, but the molecular mechanism and physiological significance remain largely unknown. Using a cell-free system for MCM loading onto plasmid DNA in Xenopus egg extracts, we found that MCM loaded onto DNA prevents DNA binding of the loading factors ORC, Cdc6, and Cdt1. We further report that a peptide of the C-terminal region of MCM3 (MCM3-C), previously implicated in the initial association with ORC/Cdc6 in budding yeast, prevents ORC/Cdc6/Cdt1 binding to DNA in the absence of MCM loading. ATP-γ-S suppresses inhibitory activities of both the MCM loaded onto DNA and the MCM3-C peptide. Other soluble factors in the extract, but neither MCM nor Cdt1, are required for the activity. Conservation of the amino acid sequences of MCM3-C and its activity in vertebrates implies a novel negative autoregulatory mechanism that interferes with MCM loading in the vicinity of licensed origins to ensure proper origin licensing.

Characterization of RyDEN (C19orf66 as an Interferon-Stimulated Cellular Inhibitor against Dengue Virus Replication.

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Youichi Suzuki

2016-01-01

Full Text Available Dengue virus (DENV is one of the most important arthropod-borne pathogens that cause life-threatening diseases in humans. However, no vaccine or specific antiviral is available for dengue. As seen in other RNA viruses, the innate immune system plays a key role in controlling DENV infection and disease outcome. Although the interferon (IFN response, which is central to host protective immunity, has been reported to limit DENV replication, the molecular details of how DENV infection is modulated by IFN treatment are elusive. In this study, by employing a gain-of-function screen using a type I IFN-treated cell-derived cDNA library, we identified a previously uncharacterized gene, C19orf66, as an IFN-stimulated gene (ISG that inhibits DENV replication, which we named Repressor of yield of DENV (RyDEN. Overexpression and gene knockdown experiments revealed that expression of RyDEN confers resistance to all serotypes of DENV in human cells. RyDEN expression also limited the replication of hepatitis C virus, Kunjin virus, Chikungunya virus, herpes simplex virus type 1, and human adenovirus. Importantly, RyDEN was considered to be a crucial effector molecule in the IFN-mediated anti-DENV response. When affinity purification-mass spectrometry analysis was performed, RyDEN was revealed to form a complex with cellular mRNA-binding proteins, poly(A-binding protein cytoplasmic 1 (PABPC1, and La motif-related protein 1 (LARP1. Interestingly, PABPC1 and LARP1 were found to be positive modulators of DENV replication. Since RyDEN influenced intracellular events on DENV replication and, suppression of protein synthesis from DENV-based reporter construct RNA was also observed in RyDEN-expressing cells, our data suggest that RyDEN is likely to interfere with the translation of DENV via interaction with viral RNA and cellular mRNA-binding proteins, resulting in the inhibition of virus replication in infected cells.

A dual character of flavonoids in influenza A virus replication and spread through modulating cell-autonomous immunity by MAPK signaling pathways

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Dong, Wenjuan; Wei, Xiuli; Zhang, Fayun; Hao, Junfeng; Huang, Feng; Zhang, Chunling; Liang, Wei

2014-01-01

Flavonoids are well known as a large class of polyphenolic compounds, which have a variety of physiological activities, including anti-influenza virus activity. The influenza A/WSN/33 infected A549 cells have been used to screen anti-influenza virus drugs from natural flavonoid compounds library. Unexpectedly, some flavonoid compounds significantly inhibited virus replication, while the others dramatically promoted virus replication. In this study, we attempted to understand these differences between flavonoid compounds in their antivirus mechanisms. Hesperidin and kaempferol were chosen as representatives of both sides, each of which exhibited the opposite effects on influenza virus replication. Our investigation revealed that the opposite effects produced by hesperidin and kaempferol on influenza virus were due to inducing the opposite cell-autonomous immune responses by selectively modulating MAP kinase pathways: hesperidin up-regulated P38 and JNK expression and activation, thus resulting in the enhanced cell-autonomous immunity; while kaempferol dramatically down-regulated p38 and JNK expression and activation, thereby suppressing cell-autonomous immunity. In addition, hesperidin restricted RNPs export from nucleus by down-regulating ERK activation, but kaempferol promoted RNPs export by up-regulating ERK activation. Our findings demonstrate that a new generation of anti-influenza virus drugs could be developed based on selective modulation of MAP kinase pathways to stimulate cell-autonomous immunity. PMID:25429875

Initiation preference at a yeast origin of replication.

Science.gov (United States)

Brewer, B J; Fangman, W L

1994-04-12

Replication origins in the yeast Saccharomyces cerevisiae are identified as autonomous replication sequence (ARS) elements. To examine the effect of origin density on replication initiation, we have analyzed the replication of a plasmid that contains two copies of the same origin, ARS1. The activation of origins and the direction that replication forks move through flanking sequences can be physically determined by analyzing replication intermediates on two-dimensional agarose gels. We find that only one of the two identical ARSs on the plasmid initiates replication on any given plasmid molecule; that is, this close spacing of ARSs results in an apparent interference between the potential origins. Moreover, in the particular plasmid that we constructed, one of the two identical copies of ARS1 is used four times more frequently than the other one. These results show that the plasmid context is critical for determining the preferred origin. This origin preference is also exhibited when the tandem copies of ARS1 are introduced into a yeast chromosome. The sequences responsible for establishing the origin preference have been identified by deletion analysis and are found to reside in a portion of the yeast URA3 gene.

Checkpoint-dependent RNR induction promotes fork restart after replicative stress.

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Morafraile, Esther C; Diffley, John F X; Tercero, José Antonio; Segurado, Mónica

2015-01-20

The checkpoint kinase Rad53 is crucial to regulate DNA replication in the presence of replicative stress. Under conditions that interfere with the progression of replication forks, Rad53 prevents Exo1-dependent fork degradation. However, although EXO1 deletion avoids fork degradation in rad53 mutants, it does not suppress their sensitivity to the ribonucleotide reductase (RNR) inhibitor hydroxyurea (HU). In this case, the inability to restart stalled forks is likely to account for the lethality of rad53 mutant cells after replication blocks. Here we show that Rad53 regulates replication restart through the checkpoint-dependent transcriptional response, and more specifically, through RNR induction. Thus, in addition to preventing fork degradation, Rad53 prevents cell death in the presence of HU by regulating RNR-expression and localization. When RNR is induced in the absence of Exo1 and RNR negative regulators, cell viability of rad53 mutants treated with HU is increased and the ability of replication forks to restart after replicative stress is restored.

UBXN1 Interferes with Rig-I-like Receptor-Mediated Antiviral Immune Response by Targeting MAVS

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Penghua Wang

2013-04-01

Full Text Available RNA viruses are sensed by RIG-I-like receptors (RLRs, which signal through a mitochondria-associated adaptor molecule, MAVS, resulting in systemic antiviral immune responses. Although RLR signaling is essential for limiting RNA virus replication, it must be stringently controlled to prevent damage from inflammation. We demonstrate here that among all tested UBX-domain-containing protein family members, UBXN1 exhibits the strongest inhibitory effect on RNA-virus-induced type I interferon response. UBXN1 potently inhibits RLR- and MAVS-induced, but not TLR3-, TLR4-, or DNA-virus-induced innate immune responses. Depletion of UBXN1 enhances virus-induced innate immune responses, including those resulting from RNA viruses such as vesicular stomatitis, Sendai, West Nile, and dengue virus infection, repressing viral replication. Following viral infection, UBXN1 is induced, binds to MAVS, interferes with intracellular MAVS oligomerization, and disrupts the MAVS/TRAF3/TRAF6 signalosome. These findings underscore a critical role of UBXN1 in the modulation of a major antiviral signaling pathway.

Modulation of Autophagy-Like Processes by Tumor Viruses

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Karl Munger

2012-06-01

Full Text Available Autophagy is an intracellular degradation pathway for long-lived proteins and organelles. This process is activated above basal levels upon cell intrinsic or environmental stress and dysregulation of autophagy has been linked to various human diseases, including those caused by viral infection. Many viruses have evolved strategies to directly interfere with autophagy, presumably to facilitate their replication or to escape immune detection. However, in some cases, modulation of autophagy appears to be a consequence of the virus disturbing the cell’s metabolic signaling networks. Here, we summarize recent advances in research at the interface of autophagy and viral infection, paying special attention to strategies that human tumor viruses have evolved.

Interference Cancellation for Hollow-Core Fiber Reference Cells

DEFF Research Database (Denmark)

Seppä, Jeremias; Merimaa, Mikko; Merimaa, Mikko

2015-01-01

Doppler-free saturated absorption spectroscopy of gases in hollow-core fiber (HCF)-based cells can be used for realizing new compact, robust, and portable frequency standards. In this paper, methods for cancelling interferences resulting from the optical connections between standard fiber and HCF...... and other factors such as varying coupling to HCF modes are investigated. Laser power modulation with simultaneous detection of ac and dc signal is used to separate saturated absorption from interferences. In addition, a technique of two piezoelectric stack actuators stretching the fiber at different...... locations is described. The presented experimental results demonstrate that 99% interference attenuation is readily attainable with the techniques. Frequency comb-referenced measurement of saturated acetylene absorption features near 1.54 μm, with fiber length and power modulation, is presented...

Second-Order Optimal Array Receivers for Synchronization of BPSK, MSK, and GMSK Signals Corrupted by Noncircular Interferences

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Chevalier Pascal

2007-01-01

Full Text Available The synchronization and/or time acquisition problem in the presence of interferences has been strongly studied these last two decades, mainly to mitigate the multiple access interferences from other users in DS/CDMA systems. Among the available receivers, only some scarce receivers may also be used in other contexts such as F/TDMA systems. However, these receivers assume implicitly or explicitly circular (or proper interferences and become suboptimal for noncircular (or improper interferences. Such interferences are characteristic in particular of radio communication networks using either rectilinear (or monodimensional modulations such as BPSK modulation or modulation becoming quasirectilinear after a preprocessing such as MSK, GMSK, or OQAM modulations. For this reason, the purpose of this paper is to introduce and to analyze the performance of second-optimal array receivers for synchronization and/or time acquisition of BPSK, MSK, and GMSK signals corrupted by noncircular interferences. For given performances and in the presence of rectilinear signal and interferences, the proposed receiver allows a reduction of the number of sensors by a factor at least equal to two.

Dependency-dependent interference: NPI interference, agreement attraction, and global pragmatic inferences

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Ming eXiang

2013-10-01

Full Text Available Previous psycholinguistics studies have shown that when forming a long distance dependency in online processing, the parser sometimes accepts a sentence even though the required grammatical constraints are only partially met. A mechanistic account of how such errors arise sheds light on both the underlying linguistic representations involved and the processing mechanisms that put such representations together. In the current study, we contrast the NPI (negative polarity items interference effect, as shown by the acceptance of an ungrammatical sentence like The bills that democratic senators have voted for will ever become law, with the well-known phenomenon of agreement attraction (The key to the cabinets are…. On the surface, these two types of errors look alike and thereby can be explained as being driven by the same source: similarity based memory interference. However, we argue that the linguistic representations involved in NPI licensing are substantially different from those of subject-verb agreement, and therefore the interference effects in each domain potentially arise from distinct sources. In particular, we show that NPI interference at least partially arises from pragmatic inferences. In a self-paced reading study with an acceptability judgment task, we showed NPI interference was modulated by participants’ general pragmatic communicative skills, as quantified by the Autism-Spectrum Quotient (Baron-Cohen 2001, especially in offline tasks. Participants with more autistic traits were actually less prone to the NPI interference effect than those with fewer autistic traits. This result contrasted with agreement attraction conditions, which were not influenced by individual pragmatic skill differences. We also show that different NPI licensors have distinct interference profiles. We discuss two kinds of interference effects for NPI licensing: memory-retrieval based and pragmatically triggered.

Deficit of entropy modulation of the EEG in schizophrenia associated to cognitive performance and symptoms. A replication study.

Science.gov (United States)

Molina, Vicente; Bachiller, Alejandro; Gomez-Pilar, Javier; Lubeiro, Alba; Hornero, Roberto; Cea-Cañas, Benjamín; Valcárcel, César; Haidar, Mahmoun-Karim; Poza, Jesús

2017-09-05

Spectral entropy (SE) is a measurement from information theory field that provides an estimation of EEG regularity and may be useful as a summary of its spectral properties. Previous studies using small samples reported a deficit of EEG entropy modulation in schizophrenia during cognitive activity. The present study is aimed at replicating this finding in a larger sample, to explore its cognitive and clinical correlates and to discard antipsychotic treatment as the main source of that deficit. We included 64 schizophrenia patients (21 first episodes, FE) and 65 healthy controls. We computed SE during performance of an odd-ball paradigm, at the windows prior (-300 to 0ms) and following (150 to 450ms) stimulus presentation. Modulation of SE was defined as the difference between post- and pre-stimulus windows. In comparison to controls, patients showed a deficit of SE modulation over frontal and central regions, also shown by FE patients. Baseline SE did not differ between patients and controls. Modulation deficit was directly associated with cognitive deficits and negative symptoms, and inversely with positive symptoms. SE modulation was not related to antipsychotic doses. Patients also showed a smaller change of median frequency (i.e., smaller slowing of oscillatory activity) of the EEG from pre- to post-stimulus windows. These results support that a deficit of fast modulation contributes to cognitive deficits and symptoms in schizophrenia patients. Copyright © 2017. Published by Elsevier B.V.

WEED INTERFERENCE IN EGGPLANT CROPS

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LUIZ JUNIOR PEREIRA MARQUES

2017-01-01

Full Text Available Uncontrolled weed growth interferes with the growth eggplants and crop yields. To control weeds, the main weed species must be identified in crop growing areas and during weed control periods, as weed species might vary in relation to management practices. Therefore, this study aimed to identify the main weed species and determine the periods of weed interference in the eggplant cultivar Nápoli when grown under certain cultural practices, including plant staking and sprout thinning. The experiment was carried out in 2014 using a randomized complete block design, with 3 replications. The treatments consisted of 11 periods of (1 increasing weed control and (2 increasing coexistence of eggplant with weeds from the first day of transplanting (0-14, 0-28, 0-42, 0-56, 0-70, 0-84, 0-98, 0-112, 0-126, 0-140, and up do day 154. Eggplant staking and sprout thinning were performed 42 days after transplanting (DAT. Weed identification and crop yield assessments were performed to determine the Period Before Interference (PBI, Total Period of Interference Prevention (TPIP, and the Critical Period of Interference Prevention (CPIP. The major weeds found in the eggplant cultivar Nápoli were Eleusine indica, Portulaca oleracea, and Cyperus rotundus. Coexistence between the weed community and the eggplant throughout the entire crop production cycle reduced eggplant fruit yield by 78%. The PBI was 29 DAT and the TPIP was 48 DAT, resulting in 19 days of CPIP.

Explicit attention interferes with selective emotion processing in human extrastriate cortex

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Junghöfer Markus

2007-02-01

Full Text Available Abstract Background Brain imaging and event-related potential studies provide strong evidence that emotional stimuli guide selective attention in visual processing. A reflection of the emotional attention capture is the increased Early Posterior Negativity (EPN for pleasant and unpleasant compared to neutral images (~150–300 ms poststimulus. The present study explored whether this early emotion discrimination reflects an automatic phenomenon or is subject to interference by competing processing demands. Thus, emotional processing was assessed while participants performed a concurrent feature-based attention task varying in processing demands. Results Participants successfully performed the primary visual attention task as revealed by behavioral performance and selected event-related potential components (Selection Negativity and P3b. Replicating previous results, emotional modulation of the EPN was observed in a task condition with low processing demands. In contrast, pleasant and unpleasant pictures failed to elicit increased EPN amplitudes compared to neutral images in more difficult explicit attention task conditions. Further analyses determined that even the processing of pleasant and unpleasant pictures high in emotional arousal is subject to interference in experimental conditions with high task demand. Taken together, performing demanding feature-based counting tasks interfered with differential emotion processing indexed by the EPN. Conclusion The present findings demonstrate that taxing processing resources by a competing primary visual attention task markedly attenuated the early discrimination of emotional from neutral picture contents. Thus, these results provide further empirical support for an interference account of the emotion-attention interaction under conditions of competition. Previous studies revealed the interference of selective emotion processing when attentional resources were directed to locations of explicitly task

Explicit attention interferes with selective emotion processing in human extrastriate cortex.

Science.gov (United States)

Schupp, Harald T; Stockburger, Jessica; Bublatzky, Florian; Junghöfer, Markus; Weike, Almut I; Hamm, Alfons O

2007-02-22

Brain imaging and event-related potential studies provide strong evidence that emotional stimuli guide selective attention in visual processing. A reflection of the emotional attention capture is the increased Early Posterior Negativity (EPN) for pleasant and unpleasant compared to neutral images (approximately 150-300 ms poststimulus). The present study explored whether this early emotion discrimination reflects an automatic phenomenon or is subject to interference by competing processing demands. Thus, emotional processing was assessed while participants performed a concurrent feature-based attention task varying in processing demands. Participants successfully performed the primary visual attention task as revealed by behavioral performance and selected event-related potential components (Selection Negativity and P3b). Replicating previous results, emotional modulation of the EPN was observed in a task condition with low processing demands. In contrast, pleasant and unpleasant pictures failed to elicit increased EPN amplitudes compared to neutral images in more difficult explicit attention task conditions. Further analyses determined that even the processing of pleasant and unpleasant pictures high in emotional arousal is subject to interference in experimental conditions with high task demand. Taken together, performing demanding feature-based counting tasks interfered with differential emotion processing indexed by the EPN. The present findings demonstrate that taxing processing resources by a competing primary visual attention task markedly attenuated the early discrimination of emotional from neutral picture contents. Thus, these results provide further empirical support for an interference account of the emotion-attention interaction under conditions of competition. Previous studies revealed the interference of selective emotion processing when attentional resources were directed to locations of explicitly task-relevant stimuli. The present data suggest

Non-canonical CRL4A/4B(CDT2 interacts with RAD18 to modulate post replication repair and cell survival.

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Sarah Sertic

Full Text Available The Cullin-4(CDT2 E3 ubiquitin ligase plays an essential role in DNA replication origin licensing directing degradation of several licensing factors at the G1/S transition in order to prevent DNA re-replication. Recently a RAD18-independent role of Cullin-4(CDT2 in PCNA monoubiquitylation has been proposed. In an effort to better understand the function of Cullin-4(CDT2 E3 ubiquitin ligase in mammalian Post-Replication Repair during an unperturbed S-phase, we show that down-regulation of Cullin-4(CDT2 leads to two distinguishable independent phenotypes in human cells that unveil at least two independent roles of Cullin-4(CDT2 in S-phase. Apart from the re-replication preventing activity, we identified a non-canonical Cullin-4(CDT2 complex, containing both CUL4A and CUL4B, associated to the COP9 signalosome, that controls a RAD18-dependent damage avoidance pathway essential during an unperturbed S-phase. Indeed, we show that the non-canonical Cullin-4A/4B(CDT2 complex binds to RAD18 and it is required to modulate RAD18 protein levels onto chromatin and the consequent dynamics of PCNA monoubiquitylation during a normal S-phase. This function prevents replication stress, ATR hyper-signaling and, ultimately, apoptosis. A very similar PRR regulatory mechanism has been recently described for Spartan. Our findings uncover a finely regulated process in mammalian cells involving Post-Replication Repair factors, COP9 signalosome and a non-canonical Cullin4-based E3 ligase which is essential to tolerate spontaneous damage and for cell survival during physiological DNA replication.

Conflict Resolution in the Genome: How Transcription and Replication Make It Work.

Science.gov (United States)

Hamperl, Stephan; Cimprich, Karlene A

2016-12-01

The complex machineries involved in replication and transcription translocate along the same DNA template, often in opposing directions and at different rates. These processes routinely interfere with each other in prokaryotes, and mounting evidence now suggests that RNA polymerase complexes also encounter replication forks in higher eukaryotes. Indeed, cells rely on numerous mechanisms to avoid, tolerate, and resolve such transcription-replication conflicts, and the absence of these mechanisms can lead to catastrophic effects on genome stability and cell viability. In this article, we review the cellular responses to transcription-replication conflicts and highlight how these inevitable encounters shape the genome and impact diverse cellular processes. Copyright © 2016 Elsevier Inc. All rights reserved.

Site-directed mutagenesis of HIV-1 vpu gene demonstrates two clusters of replication-defective mutants with distinct ability to down-modulate cell surface CD4 and tetherin

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Masako Nomaguchi

2010-11-01

Full Text Available HIV-1 Vpu acts positively on viral infectivity by mediating CD4 degradation in endoplasmic reticulum and enhances virion release by counteracting a virion release restriction factor, tetherin. In order to define the impact of Vpu activity on HIV-1 replication, we have generated a series of site-specific proviral vpu mutants. Of fifteen mutants examined, seven exhibited a replication-defect similar to that of a vpu-deletion mutant in a lymphocyte cell line H9. These mutations clustered in narrow regions within transmembrane domain (TMD and cytoplasmic domain (CTD. Replication-defective mutants displayed the reduced ability to enhance virion release from a monolayer cell line HEp2 without exception. Upon transfection with Vpu expression vectors, neither TMD mutants nor CTD mutants blocked CD4 expression at the cell surface in another monolayer cell line MAGI. While TMD mutants were unable to down-modulate cell surface tetherin in HEp2 cells, CTD mutants did quite efficiently. Confocal microscopy analysis revealed the difference of intracellular localization between TMD and CTD mutants. In total, replication capability of HIV-1 carrying vpu mutations correlates well with the ability of Vpu to enhance virion release and to impede the cell surface expression of CD4 but not with the ability to down-modulate cell surface tetherin. Our results here suggest that efficient viral replication requires not only down-regulation of cell surface tetherin but also its degradation.

Spin wave scattering and interference in ferromagnetic cross

Energy Technology Data Exchange (ETDEWEB)

Nanayakkara, Kasuni; Kozhanov, Alexander [Department of Physics and Astronomy, Georgia State University, Atlanta, Georgia 30303 (United States); Center for Nano Optics, Georgia State University, Atlanta, Georgia 30303 (United States); Jacob, Ajey P. [Exploratory Research Device and Integration, GLOBALFOUNDRIES, Albany, New York 12203 (United States)

2015-10-28

Magnetostatic spin wave scattering and interference across a CoTaZr ferromagnetic spin wave waveguide cross junction were investigated experimentally and by micromagnetic simulations. It is observed that the phase of the scattered waves is dependent on the wavelength, geometry of the junction, and scattering direction. It is found that destructive and constructive interference of the spin waves generates switching characteristics modulated by the input phase of the spin waves. Micromagnetic simulations are used to analyze experimental data and simulate the spin wave scattering and interference.

Plasmid P1 replication: negative control by repeated DNA sequences.

OpenAIRE

Chattoraj, D; Cordes, K; Abeles, A

1984-01-01

The incompatibility locus, incA, of the unit-copy plasmid P1 is contained within a fragment that is essentially a set of nine 19-base-pair repeats. One or more copies of the fragment destabilizes the plasmid when present in trans. Here we show that extra copies of incA interfere with plasmid DNA replication and that a deletion of most of incA increases plasmid copy number. Thus, incA is not essential for replication but is required for its control. When cloned in a high-copy-number vector, pi...

Persistency and flexibility of complex brain networks underlie dual-task interference.

Science.gov (United States)

Alavash, Mohsen; Hilgetag, Claus C; Thiel, Christiane M; Gießing, Carsten

2015-09-01

Previous studies on multitasking suggest that performance decline during concurrent task processing arises from interfering brain modules. Here, we used graph-theoretical network analysis to define functional brain modules and relate the modular organization of complex brain networks to behavioral dual-task costs. Based on resting-state and task fMRI we explored two organizational aspects potentially associated with behavioral interference when human subjects performed a visuospatial and speech task simultaneously: the topological overlap between persistent single-task modules, and the flexibility of single-task modules in adaptation to the dual-task condition. Participants showed a significant decline in visuospatial accuracy in the dual-task compared with single visuospatial task. Global analysis of topological similarity between modules revealed that the overlap between single-task modules significantly correlated with the decline in visuospatial accuracy. Subjects with larger overlap between single-task modules showed higher behavioral interference. Furthermore, lower flexible reconfiguration of single-task modules in adaptation to the dual-task condition significantly correlated with larger decline in visuospatial accuracy. Subjects with lower modular flexibility showed higher behavioral interference. At the regional level, higher overlap between single-task modules and less modular flexibility in the somatomotor cortex positively correlated with the decline in visuospatial accuracy. Additionally, higher modular flexibility in cingulate and frontal control areas and lower flexibility in right-lateralized nodes comprising the middle occipital and superior temporal gyri supported dual-tasking. Our results suggest that persistency and flexibility of brain modules are important determinants of dual-task costs. We conclude that efficient dual-tasking benefits from a specific balance between flexibility and rigidity of functional brain modules. © 2015 Wiley

Utility-based early modulation of processing distracting stimulus information.

Science.gov (United States)

Wendt, Mike; Luna-Rodriguez, Aquiles; Jacobsen, Thomas

2014-12-10

Humans are selective information processors who efficiently prevent goal-inappropriate stimulus information to gain control over their actions. Nonetheless, stimuli, which are both unnecessary for solving a current task and liable to cue an incorrect response (i.e., "distractors"), frequently modulate task performance, even when consistently paired with a physical feature that makes them easily discernible from target stimuli. Current models of cognitive control assume adjustment of the processing of distractor information based on the overall distractor utility (e.g., predictive value regarding the appropriate response, likelihood to elicit conflict with target processing). Although studies on distractor interference have supported the notion of utility-based processing adjustment, previous evidence is inconclusive regarding the specificity of this adjustment for distractor information and the stage(s) of processing affected. To assess the processing of distractors during sensory-perceptual phases we applied EEG recording in a stimulus identification task, involving successive distractor-target presentation, and manipulated the overall distractor utility. Behavioral measures replicated previously found utility modulations of distractor interference. Crucially, distractor-evoked visual potentials (i.e., posterior N1) were more pronounced in high-utility than low-utility conditions. This effect generalized to distractors unrelated to the utility manipulation, providing evidence for item-unspecific adjustment of early distractor processing to the experienced utility of distractor information. Copyright © 2014 the authors 0270-6474/14/3416720-06$15.00/0.

Decoupled Modulation Control

Energy Technology Data Exchange (ETDEWEB)

Wang, Shaobu; Huang, Renke; Huang, Zhenyu; Diao, Ruisheng

2016-06-03

The objective of this research work is to develop decoupled modulation control methods for damping inter-area oscillations with low frequencies, so the damping control can be more effective and easier to design with less interference among different oscillation modes in the power system. A signal-decoupling algorithm was developed that can enable separation of multiple oscillation frequency contents and extraction of a “pure” oscillation frequency mode that are fed into Power System Stabilizers (PSSs) as the modulation input signals. As a result, instead of introducing interferences between different oscillation modes from the traditional approaches, the output of the new PSS modulation control signal mainly affects only one oscillation mode of interest. The new decoupled modulation damping control algorithm has been successfully developed and tested on the standard IEEE 4-machine 2-area test system and a minniWECC system. The results are compared against traditional modulation controls, which demonstrates the validity and effectiveness of the newly-developed decoupled modulation damping control algorithm.

Overcoming natural replication barriers: differential helicase requirements.

Science.gov (United States)

Anand, Ranjith P; Shah, Kartik A; Niu, Hengyao; Sung, Patrick; Mirkin, Sergei M; Freudenreich, Catherine H

2012-02-01

DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers, we analyzed fork progression through them in wild-type and mutant yeast cells, using 2-dimensional gel-electrophoretic analysis of the replication intermediates. We show that the Srs2 protein facilitates replication of hairpin-forming CGG/CCG repeats and prevents chromosome fragility at the repeat, whereas it does not affect replication of G-quadruplex forming sequences or a protein-bound repeat. Srs2 helicase activity is required for hairpin unwinding and fork progression. Also, the PCNA binding domain of Srs2 is required for its in vivo role of replication through hairpins. In contrast, the absence of Sgs1 or Pif1 helicases did not inhibit replication through structural barriers, though Pif1 did facilitate replication of a telomeric protein barrier. Interestingly, replication through a protein barrier but not a DNA structure barrier was modulated by nucleotide pool levels, illuminating a different mechanism by which cells can regulate fork progression through protein-mediated stall sites. Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures.

Anti-replicative recombinant 5S rRNA molecules can modulate the mtDNA heteroplasmy in a glucose-dependent manner.

Science.gov (United States)

Loutre, Romuald; Heckel, Anne-Marie; Jeandard, Damien; Tarassov, Ivan; Entelis, Nina

2018-01-01

between mutant and wild type mtDNA molecules is not a consequence of a random repopulation of depleted pool of mtDNA genomes. The heteroplasmy change could be also modulated by cell growth conditions, namely increased by cells culturing in a carbohydrate-free medium, thus forcing them to use oxidative phosphorylation and providing a selective advantage for cells with improved respiration capacities. We discuss the advantages and limitations of this approach and propose further development of the anti-replicative strategy based on the RNA import into human mitochondria.

Inhibition of herpesvirus and influenza virus replication by blocking polymerase subunit interactions.

Science.gov (United States)

Palù, Giorgio; Loregian, Arianna

2013-09-01

Protein-protein interactions (PPIs) play a key role in many biological processes, including virus replication in the host cell. Since most of the PPIs are functionally essential, a possible strategy to inhibit virus replication is based on the disruption of viral protein complexes by peptides or small molecules that interfere with subunit interactions. In particular, an attractive target for antiviral drugs is the binding between the subunits of essential viral enzymes. This review describes the development of new antiviral compounds that inhibit herpesvirus and influenza virus replication by blocking interactions between subunit proteins of their polymerase complexes. Copyright © 2013 Elsevier B.V. All rights reserved.

The eukaryotic translation initiation factor 3 subunit L protein interacts with Flavivirus NS5 and may modulate yellow fever virus replication.

Science.gov (United States)

Morais, Ana Ts; Terzian, Ana Cb; Duarte, Danilo Vb; Bronzoni, Roberta Vm; Madrid, Maria Cfs; Gavioli, Arieli F; Gil, Laura Hvg; Oliveira, Amanda G; Zanelli, Cleslei F; Valentini, Sandro R; Rahal, Paula; Nogueira, Mauricio L

2013-06-22

Yellow fever virus (YFV) belongs to the Flavivirus genus and causes an important disease. An alarming resurgence of viral circulation and the expansion of YFV-endemic zones have been detected in Africa and South America in recent years. NS5 is a viral protein that contains methyltransferase and RNA-dependent RNA polymerase (RdRp) domains, which are essential for viral replication, and the interactions between NS5 and cellular proteins have been studied to better understand viral replication. The aim of this study was to characterize the interaction of the NS5 protein with eukaryotic translation initiation factor 3 subunit L (eIF3L) and to evaluate the role of eIF3L in yellow fever replication. To identify interactions of YFV NS5 with cellular proteins, we performed a two-hybrid screen using the YFV NS5 RdRp domain as bait with a human cDNA library, and RNApol deletion mutants were generated and analyzed using the two-hybrid system for mapping the interactions. The RNApol region involved was segmented into three fragments and analyzed using an eIF3L-expressing yeast strain. To map the NS5 residues that are critical for the interactions, we performed site-direct mutagenesis in segment 3 of the interaction domain (ID) and confirmed the interaction using in vitro assays and in vivo coimmunoprecipitation. The significance of eIF3L for YFV replication was investigated using eIF3L overexpression and RNA interference. In this work, we describe and characterize the interaction of NS5 with the translation factor eIF3L. The interaction between NS5 and eIF3L was confirmed using in vitro binding and in vivo coimmunoprecipitation assays. This interaction occurs at a region (the interaction domain of the RNApol domain) that is conserved in several flaviviruses and that is, therefore, likely to be relevant to the genus. eIF3L overexpression and plaque reduction assays showed a slight effect on YFV replication, indicating that the interaction of eIF3L with YFV NS5 may play a role

Converging evidence for control of color-word Stroop interference at the item level.

Science.gov (United States)

Bugg, Julie M; Hutchison, Keith A

2013-04-01

Prior studies have shown that cognitive control is implemented at the list and context levels in the color-word Stroop task. At first blush, the finding that Stroop interference is reduced for mostly incongruent items as compared with mostly congruent items (i.e., the item-specific proportion congruence [ISPC] effect) appears to provide evidence for yet a third level of control, which modulates word reading at the item level. However, evidence to date favors the view that ISPC effects reflect the rapid prediction of high-contingency responses and not item-specific control. In Experiment 1, we first show that an ISPC effect is obtained when the relevant dimension (i.e., color) signals proportion congruency, a problematic pattern for theories based on differential response contingencies. In Experiment 2, we replicate and extend this pattern by showing that item-specific control settings transfer to new stimuli, ruling out alternative frequency-based accounts. In Experiment 3, we revert to the traditional design in which the irrelevant dimension (i.e., word) signals proportion congruency. Evidence for item-specific control, including transfer of the ISPC effect to new stimuli, is apparent when 4-item sets are employed but not when 2-item sets are employed. We attribute this pattern to the absence of high-contingency responses on incongruent trials in the 4-item set. These novel findings provide converging evidence for reactive control of color-word Stroop interference at the item level, reveal theoretically important factors that modulate reliance on item-specific control versus contingency learning, and suggest an update to the item-specific control account (Bugg, Jacoby, & Chanani, 2011).

A loss of function analysis of host factors influencing Vaccinia virus replication by RNA interference.

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Philippa M Beard

Full Text Available Vaccinia virus (VACV is a large, cytoplasmic, double-stranded DNA virus that requires complex interactions with host proteins in order to replicate. To explore these interactions a functional high throughput small interfering RNA (siRNA screen targeting 6719 druggable cellular genes was undertaken to identify host factors (HF influencing the replication and spread of an eGFP-tagged VACV. The experimental design incorporated a low multiplicity of infection, thereby enhancing detection of cellular proteins involved in cell-to-cell spread of VACV. The screen revealed 153 pro- and 149 anti-viral HFs that strongly influenced VACV replication. These HFs were investigated further by comparisons with transcriptional profiling data sets and HFs identified in RNAi screens of other viruses. In addition, functional and pathway analysis of the entire screen was carried out to highlight cellular mechanisms involved in VACV replication. This revealed, as anticipated, that many pro-viral HFs are involved in translation of mRNA and, unexpectedly, suggested that a range of proteins involved in cellular transcriptional processes and several DNA repair pathways possess anti-viral activity. Multiple components of the AMPK complex were found to act as pro-viral HFs, while several septins, a group of highly conserved GTP binding proteins with a role in sequestering intracellular bacteria, were identified as strong anti-viral VACV HFs. This screen has identified novel and previously unexplored roles for cellular factors in poxvirus replication. This advancement in our understanding of the VACV life cycle provides a reliable knowledge base for the improvement of poxvirus-based vaccine vectors and development of anti-viral theraputics.

Interference of two photons in parametric down conversion

International Nuclear Information System (INIS)

Ghosh, R.; Hong, C.K.; Ou, Z.Y.; Mandel, L.

1986-01-01

A theoretical treatment is given of the process in which the two photons produced simultaneously in the parametric frequency splitting of light are allowed to interfere. It is shown that, while there is no interference in the usual sense involving quantities that are of the second order in the field, fourth-order interference effects are present. These may be revealed by measuring the joint probability of detecting two photons at two points x,x' in the interference plane with photoelectric detectors as a function of the separation x-x'. The probability exhibits a cosine modulation with x-x', with visibility that can approach 100%, even though the integration time in the experiment may greatly exceed the reciprocal bandwidth of the photons. The interference effect has a nonclassical origin and implies a violation of local realism in the highly correlated two-photon state

Signal noise/interferer combiner unit programmable (SINCUP)

Science.gov (United States)

Martinezdepison, Emilio

1988-12-01

The Signal Noise Interferer Combiner Unit Programmable (SINCUP) has been developed to facilitate laboratory performance testing of Very Low Frequency (VLF/Low Frequency (LF) receivers. To accomplish this, the unit allows the combining in controlled amounts of various real-world environmental and manmade interference with an information carrying signal. The externally modulated signal is combined with internally/externally generated Gaussian noise and/or with an internally/externally generated interferer. In order to test modern digital processing techniques, such as Adaptive Null Steering, Eigenvector Sorting, and Widrow-Hoff adaptive filters, SINCUP is capable of generating and meeting much higher signal-to-noise plus interference ratios than earlier channel simulators. The present software has been written to accommodate a dynamic signal-to-noise ratio (SNR) range from -60 to +60 dB. Higher dynamic range units could be implemented.

Implicit proactive interference, age, and automatic versus controlled retrieval strategies.

Science.gov (United States)

Ikier, Simay; Yang, Lixia; Hasher, Lynn

2008-05-01

We assessed the extent to which implicit proactive interference results from automatic versus controlled retrieval among younger and older adults. During a study phase, targets (e.g., "ALLERGY") either were or were not preceded by nontarget competitors (e.g., "ANALOGY"). After a filled interval, the participants were asked to complete word fragments, some of which cued studied words (e.g., "A_L_ _GY"). Retrieval strategies were identified by the difference in response speed between a phase containing fragments that cued only new words and a phase that included a mix of fragments cuing old and new words. Previous results were replicated: Proactive interference was found in implicit memory, and the negative effects were greater for older than for younger adults. Novel findings demonstrate two retrieval processes that contribute to interference: an automatic one that is age invariant and a controlled process that can reduce the magnitude of the automatic interference effects. The controlled process, however, is used effectively only by younger adults. This pattern of findings potentially explains age differences in susceptibility to proactive interference.

Fluoxetine Is a Potent Inhibitor of Coxsackievirus Replication

OpenAIRE

Zuo, Jun; Quinn, Kevin K.; Kye, Steve; Cooper, Paige; Damoiseaux, Robert; Krogstad, Paul

2012-01-01

No antiviral drugs currently exist for the treatment of enterovirus infections, which are often severe and potentially life threatening. Molecular screening of small molecule libraries identified fluoxetine, a selective serotonin reuptake inhibitor, as a potent inhibitor of coxsackievirus replication. Fluoxetine did not interfere with either viral entry or translation of the viral genome. Instead, fluoxetine and its metabolite norfluoxetine markedly reduced the synthesis of viral RNA and prot...

A single antenna interference cancellation and adaptive technique based on ALOE

Directory of Open Access Journals (Sweden)

Xu Han

2017-02-01

Full Text Available A new type of single antenna interference cancellation (SAIC algorithm based on ALOE filtering module is introduced for co-channel interference cancellation in GSM/GPRS/EDGE downlink without changing the link structure of traditional receiver.Meanwhile,an adjacent frequency adaptive detection based on power spectrum estimation method is introduced to solve adjacent frequency interference and complex interference.Compared with traditional energy noise estimation method,the new method has simpler structure,less complexity,and can effectively improve the adaptability for various scenarios.The simulation results show that it can raise the resistance to co-channel frequency interference and adjacent frequency interference in multimode chips with low complexity,which improves the quality of 2G voice communication.

Frequent video game players resist perceptual interference.

Directory of Open Access Journals (Sweden)

Aaron V Berard

Full Text Available Playing certain types of video games for a long time can improve a wide range of mental processes, from visual acuity to cognitive control. Frequent gamers have also displayed generalized improvements in perceptual learning. In the Texture Discrimination Task (TDT, a widely used perceptual learning paradigm, participants report the orientation of a target embedded in a field of lines and demonstrate robust over-night improvement. However, changing the orientation of the background lines midway through TDT training interferes with overnight improvements in overall performance on TDT. Interestingly, prior research has suggested that this effect will not occur if a one-hour break is allowed in between the changes. These results have suggested that after training is over, it may take some time for learning to become stabilized and resilient against interference. Here, we tested whether frequent gamers have faster stabilization of perceptual learning compared to non-gamers and examined the effect of daily video game playing on interference of training of TDT with one background orientation on perceptual learning of TDT with a different background orientation. As a result, we found that non-gamers showed overnight performance improvement only on one background orientation, replicating previous results with the interference in TDT. In contrast, frequent gamers demonstrated overnight improvements in performance with both background orientations, suggesting that they are better able to overcome interference in perceptual learning. This resistance to interference suggests that video game playing not only enhances the amplitude and speed of perceptual learning but also leads to faster and/or more robust stabilization of perceptual learning.

Frequent video game players resist perceptual interference.

Science.gov (United States)

Berard, Aaron V; Cain, Matthew S; Watanabe, Takeo; Sasaki, Yuka

2015-01-01

Playing certain types of video games for a long time can improve a wide range of mental processes, from visual acuity to cognitive control. Frequent gamers have also displayed generalized improvements in perceptual learning. In the Texture Discrimination Task (TDT), a widely used perceptual learning paradigm, participants report the orientation of a target embedded in a field of lines and demonstrate robust over-night improvement. However, changing the orientation of the background lines midway through TDT training interferes with overnight improvements in overall performance on TDT. Interestingly, prior research has suggested that this effect will not occur if a one-hour break is allowed in between the changes. These results have suggested that after training is over, it may take some time for learning to become stabilized and resilient against interference. Here, we tested whether frequent gamers have faster stabilization of perceptual learning compared to non-gamers and examined the effect of daily video game playing on interference of training of TDT with one background orientation on perceptual learning of TDT with a different background orientation. As a result, we found that non-gamers showed overnight performance improvement only on one background orientation, replicating previous results with the interference in TDT. In contrast, frequent gamers demonstrated overnight improvements in performance with both background orientations, suggesting that they are better able to overcome interference in perceptual learning. This resistance to interference suggests that video game playing not only enhances the amplitude and speed of perceptual learning but also leads to faster and/or more robust stabilization of perceptual learning.

Cyclophilin B facilitates the replication of Orf virus.

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Zhao, Kui; Li, Jida; He, Wenqi; Song, Deguang; Zhang, Ximu; Zhang, Di; Zhou, Yanlong; Gao, Feng

2017-06-15

Viruses interact with host cellular factors to construct a more favourable environment for their efficient replication. Expression of cyclophilin B (CypB), a cellular peptidyl-prolyl cis-trans isomerase (PPIase), was found to be significantly up-regulated. Recently, a number of studies have shown that CypB is important in the replication of several viruses, including Japanese encephalitis virus (JEV), hepatitis C virus (HCV) and human papillomavirus type 16 (HPV 16). However, the function of cellular CypB in ORFV replication has not yet been explored. Suppression subtractive hybridization (SSH) technique was applied to identify genes differentially expressed in the ORFV-infected MDBK cells at an early phase of infection. Cellular CypB was confirmed to be significantly up-regulated by quantitative reverse transcription-PCR (qRT-PCR) analysis and Western blotting. The role of CypB in ORFV infection was further determined using Cyclosporin A (CsA) and RNA interference (RNAi). Effect of CypB gene silencing on ORFV replication by 50% tissue culture infectious dose (TCID 50 ) assay and qRT-PCR detection. In the present study, CypB was found to be significantly up-regulated in the ORFV-infected MDBK cells at an early phase of infection. Cyclosporin A (CsA) exhibited suppressive effects on ORFV replication through the inhibition of CypB. Silencing of CypB gene inhibited the replication of ORFV in MDBK cells. In conclusion, these data suggest that CypB is critical for the efficient replication of the ORFV genome. Cellular CypB was confirmed to be significantly up-regulated in the ORFV-infected MDBK cells at an early phase of infection, which could effectively facilitate the replication of ORFV.

Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses.

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Hamperl, Stephan; Bocek, Michael J; Saldivar, Joshua C; Swigut, Tomek; Cimprich, Karlene A

2017-08-10

Conflicts between transcription and replication are a potent source of DNA damage. Co-transcriptional R-loops could aggravate such conflicts by creating an additional barrier to replication fork progression. Here, we use a defined episomal system to investigate how conflict orientation and R-loop formation influence genome stability in human cells. R-loops, but not normal transcription complexes, induce DNA breaks and orientation-specific DNA damage responses during conflicts with replication forks. Unexpectedly, the replisome acts as an orientation-dependent regulator of R-loop levels, reducing R-loops in the co-directional (CD) orientation but promoting their formation in the head-on (HO) orientation. Replication stress and deregulated origin firing increase the number of HO collisions leading to genome-destabilizing R-loops. Our findings connect DNA replication to R-loop homeostasis and suggest a mechanistic basis for genome instability resulting from deregulated DNA replication, observed in cancer and other disease states. Copyright © 2017 Elsevier Inc. All rights reserved.

Promotion of Hendra Virus Replication by MicroRNA 146a

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Marsh, Glenn A.; Jenkins, Kristie A.; Gantier, Michael P.; Tizard, Mark L.; Middleton, Deborah; Lowenthal, John W.; Haining, Jessica; Izzard, Leonard; Gough, Tamara J.; Deffrasnes, Celine; Stambas, John; Robinson, Rachel; Heine, Hans G.; Pallister, Jackie A.; Foord, Adam J.; Bean, Andrew G.; Wang, Lin-Fa

2013-01-01

Hendra virus is a highly pathogenic zoonotic paramyxovirus in the genus Henipavirus. Thirty-nine outbreaks of Hendra virus have been reported since its initial identification in Queensland, Australia, resulting in seven human infections and four fatalities. Little is known about cellular host factors impacting Hendra virus replication. In this work, we demonstrate that Hendra virus makes use of a microRNA (miRNA) designated miR-146a, an NF-κB-responsive miRNA upregulated by several innate immune ligands, to favor its replication. miR-146a is elevated in the blood of ferrets and horses infected with Hendra virus and is upregulated by Hendra virus in human cells in vitro. Blocking miR-146a reduces Hendra virus replication in vitro, suggesting a role for this miRNA in Hendra virus replication. In silico analysis of miR-146a targets identified ring finger protein (RNF)11, a member of the A20 ubiquitin editing complex that negatively regulates NF-κB activity, as a novel component of Hendra virus replication. RNA interference-mediated silencing of RNF11 promotes Hendra virus replication in vitro, suggesting that increased NF-κB activity aids Hendra virus replication. Furthermore, overexpression of the IκB superrepressor inhibits Hendra virus replication. These studies are the first to demonstrate a host miRNA response to Hendra virus infection and suggest an important role for host miRNAs in Hendra virus disease. PMID:23345523

Modulation of alpha oscillations is required for the suppression of semantic interference.

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Melnik, Natalia; Mapelli, Igor; Özkurt, Tolga Esat

2017-10-01

Recent findings on alpha band oscillations suggest their important role in memory consolidation and suppression of external distractors such as environmental noise. However, less attention was given to the phenomenon of internal distracting information being solely inherent to the stimuli content. Human memory may be prone to internal distractions caused by semantic relatedness between the meaning of words (e.g., atom, neutron, nucleus, etc.) to be encoded, i.e., semantic interference. Our study investigates the brain oscillatory dynamics behind the semantic interference phenomenon, whose possible outcome is known as false memories. In this direction, Deese-Roediger-McDermott word lists were appropriated for a modified Sternberg paradigm in auditory modality. Participants received semantically related and unrelated word lists via headphones while EEG data were acquired. Semantic interference triggered the false memory rates to be higher than those of other types of memory errors. Analysis demonstrated that the upper part of alpha band (∼10-12Hz) power decreases on parieto-occipital channels in the retention interval, prior to the probe item for semantically related condition. Our study elucidates the oscillatory mechanisms behind semantic interference by relying on alpha functional inhibition theory. Copyright © 2017 Elsevier Inc. All rights reserved.

Performance of barcode scanner using peak detection with interference from LED lamps

NARCIS (Netherlands)

Deng, X.; Zijlstra, P.; Zhang, J.; Wu, Y.; Zhou, G.; Linnartz, J.-P.

2015-01-01

This paper presents a new model for barcode scanners that suffer from the interference of LED lamps, to quantify the system performance in terms of Timing Signal-to-Interference Ratio (TSIR), particularly as a function of modulation depth and frequency of the flicker in the LED lighting. Physical

Distributed strain measurement using modal interference in a birefringent optical fiber

International Nuclear Information System (INIS)

Kumar, Dilip; Sengupta, S; Ghorai, S K

2008-01-01

We propose a method based on modal interference in a birefringent optical fiber for distributed strain measurement. A frequency-modulated optical signal from a laser diode was launched in a birefringent fiber whose 'V' number was set in the range 2.405–3.831. The beat signal produced due to the interference of two lower order modes LP 01 and LP 11 was detected in a photodetector. The change in propagation constants between two modes under loading conditions leads to a phase variation of interference signal. The amplitude of the beat frequency was measured in the frequency domain by varying the modulating frequency, and it provides the measurand distribution along the beam. Results for strain distribution of a simply supported beam (51.0 cm × 3.0 cm × 0.6 cm) for an applied load of 250–1500 g are presented

Hyperthermia stimulates HIV-1 replication.

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Ferdinand Roesch

Full Text Available HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C and Heat Shock Proteins (HSPs modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.

Energy detection UWB system based on pulse width modulation

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Song Cui

2014-05-01

Full Text Available A new energy detection ultra-wideband system based on pulse width modulation is proposed. The bit error rate (BER performance of this new system is slightly worst than that of a pulse position modulation (PPM system in additive white Gaussian noise channels. In multipath channels, this system does not suffer from cross-modulation interference as PPM, so it can achieve better BER performance than PPM when cross-modulation interference occurs. In addition, when synchronisation errors occur, this system is more robust than PPM.

Interference Characterization in Downlink Li-Fi Optical Attocell Networks

OpenAIRE

Surampudi, Atchutananda; Ganti, Radha Krishna

2017-01-01

Wireless access to data using visible light, popularly known as light-fidelity (Li-Fi), is one of the key emerging technologies which promises huge bandwidths and data rates. In Li-Fi, the data is modulated on optical intensities and transmitted and detected using light-emitting-diodes (LED) and photodiodes respectively. A network of such LED access points illuminates a given region in the form of attocells. Akin, to wireless networks, co-channel interference or simply interference is a major...

Active RNA replication of hepatitis C virus downregulates CD81 expression.

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Ke, Po-Yuan; Chen, Steve S-L

2013-01-01

So far how hepatitis C virus (HCV) replication modulates subsequent virus growth and propagation still remains largely unknown. Here we determine the impact of HCV replication status on the consequential virus growth by comparing normal and high levels of HCV RNA expression. We first engineered a full-length, HCV genotype 2a JFH1 genome containing a blasticidin-resistant cassette inserted at amino acid residue of 420 in nonstructural (NS) protein 5A, which allowed selection of human hepatoma Huh7 cells stably-expressing HCV. Short-term establishment of HCV stable cells attained a highly-replicating status, judged by higher expressions of viral RNA and protein as well as higher titer of viral infectivity as opposed to cells harboring the same genome without selection. Interestingly, maintenance of highly-replicating HCV stable cells led to decreased susceptibility to HCV pseudotyped particle (HCVpp) infection and downregulated cell surface level of CD81, a critical HCV entry (co)receptor. The decreased CD81 cell surface expression occurred through reduced total expression and cytoplasmic retention of CD81 within an endoplasmic reticulum -associated compartment. Moreover, productive viral RNA replication in cells harboring a JFH1 subgenomic replicon containing a similar blasticidin resistance gene cassette in NS5A and in cells robustly replicating full-length infectious genome also reduced permissiveness to HCVpp infection through decreasing the surface expression of CD81. The downregulation of CD81 surface level in HCV RNA highly-replicating cells thus interfered with reinfection and led to attenuated viral amplification. These findings together indicate that the HCV RNA replication status plays a crucial determinant in HCV growth by modulating the expression and intracellular localization of CD81.

Active RNA replication of hepatitis C virus downregulates CD81 expression.

Directory of Open Access Journals (Sweden)

Po-Yuan Ke

Full Text Available So far how hepatitis C virus (HCV replication modulates subsequent virus growth and propagation still remains largely unknown. Here we determine the impact of HCV replication status on the consequential virus growth by comparing normal and high levels of HCV RNA expression. We first engineered a full-length, HCV genotype 2a JFH1 genome containing a blasticidin-resistant cassette inserted at amino acid residue of 420 in nonstructural (NS protein 5A, which allowed selection of human hepatoma Huh7 cells stably-expressing HCV. Short-term establishment of HCV stable cells attained a highly-replicating status, judged by higher expressions of viral RNA and protein as well as higher titer of viral infectivity as opposed to cells harboring the same genome without selection. Interestingly, maintenance of highly-replicating HCV stable cells led to decreased susceptibility to HCV pseudotyped particle (HCVpp infection and downregulated cell surface level of CD81, a critical HCV entry (coreceptor. The decreased CD81 cell surface expression occurred through reduced total expression and cytoplasmic retention of CD81 within an endoplasmic reticulum -associated compartment. Moreover, productive viral RNA replication in cells harboring a JFH1 subgenomic replicon containing a similar blasticidin resistance gene cassette in NS5A and in cells robustly replicating full-length infectious genome also reduced permissiveness to HCVpp infection through decreasing the surface expression of CD81. The downregulation of CD81 surface level in HCV RNA highly-replicating cells thus interfered with reinfection and led to attenuated viral amplification. These findings together indicate that the HCV RNA replication status plays a crucial determinant in HCV growth by modulating the expression and intracellular localization of CD81.

An upstream open reading frame modulates ebola virus polymerase translation and virus replication.

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Reed S Shabman

2013-01-01

Full Text Available Ebolaviruses, highly lethal zoonotic pathogens, possess longer genomes than most other non-segmented negative-strand RNA viruses due in part to long 5' and 3' untranslated regions (UTRs present in the seven viral transcriptional units. To date, specific functions have not been assigned to these UTRs. With reporter assays, we demonstrated that the Zaire ebolavirus (EBOV 5'-UTRs lack internal ribosomal entry site function. However, the 5'-UTRs do differentially regulate cap-dependent translation when placed upstream of a GFP reporter gene. Most dramatically, the 5'-UTR derived from the viral polymerase (L mRNA strongly suppressed translation of GFP compared to a β-actin 5'-UTR. The L 5'-UTR is one of four viral genes to possess upstream AUGs (uAUGs, and ablation of each uAUG enhanced translation of the primary ORF (pORF, most dramatically in the case of the L 5'-UTR. The L uAUG was sufficient to initiate translation, is surrounded by a "weak" Kozak sequence and suppressed pORF translation in a position-dependent manner. Under conditions where eIF2α was phosphorylated, the presence of the uORF maintained translation of the L pORF, indicating that the uORF modulates L translation in response to cellular stress. To directly address the role of the L uAUG in virus replication, a recombinant EBOV was generated in which the L uAUG was mutated to UCG. Strikingly, mutating two nucleotides outside of previously-defined protein coding and cis-acting regulatory sequences attenuated virus growth to titers 10-100-fold lower than a wild-type virus in Vero and A549 cells. The mutant virus also exhibited decreased viral RNA synthesis as early as 6 hours post-infection and enhanced sensitivity to the stress inducer thapsigargin. Cumulatively, these data identify novel mechanisms by which EBOV regulates its polymerase expression, demonstrate their relevance to virus replication and identify a potential therapeutic target.

Amplitude modulation detection with concurrent frequency modulation.

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Nagaraj, Naveen K

2016-09-01

Human speech consists of concomitant temporal modulations in amplitude and frequency that are crucial for speech perception. In this study, amplitude modulation (AM) detection thresholds were measured for 550 and 5000 Hz carriers with and without concurrent frequency modulation (FM), at AM rates crucial for speech perception. Results indicate that adding 40 Hz FM interferes with AM detection, more so for 5000 Hz carrier and for frequency deviations exceeding the critical bandwidth of the carrier frequency. These findings suggest that future cochlear implant processors, encoding speech fine-structures may consider limiting the FM to narrow bandwidth and to low frequencies.

Facilitation and interference in naming: A consequence of the same learning process?

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Hughes, Julie W; Schnur, Tatiana T

2017-08-01

Our success with naming depends on what we have named previously, a phenomenon thought to reflect learning processes. Repeatedly producing the same name facilitates language production (i.e., repetition priming), whereas producing semantically related names hinders subsequent performance (i.e., semantic interference). Semantic interference is found whether naming categorically related items once (continuous naming) or multiple times (blocked cyclic naming). A computational model suggests that the same learning mechanism responsible for facilitation in repetition creates semantic interference in categorical naming (Oppenheim, Dell, & Schwartz, 2010). Accordingly, we tested the predictions that variability in semantic interference is correlated across categorical naming tasks and is caused by learning, as measured by two repetition priming tasks (picture-picture repetition priming, Exp. 1; definition-picture repetition priming, Exp. 2, e.g., Wheeldon & Monsell, 1992). In Experiment 1 (77 subjects) semantic interference and repetition priming effects were robust, but the results revealed no relationship between semantic interference effects across contexts. Critically, learning (picture-picture repetition priming) did not predict semantic interference effects in either task. We replicated these results in Experiment 2 (81 subjects), finding no relationship between semantic interference effects across tasks or between semantic interference effects and learning (definition-picture repetition priming). We conclude that the changes underlying facilitatory and interfering effects inherent to lexical access are the result of distinct learning processes where multiple mechanisms contribute to semantic interference in naming. Copyright © 2017 Elsevier B.V. All rights reserved.

Across-Task Conflict Regulation: A Replication Failure

Science.gov (United States)

Runger, Dennis; Schwager, Sabine; Frensch, Peter A.

2010-01-01

Fernandez-Duque and Knight (2008, Experiment 4) described an across-task effect of endogenously generated, anticipatory control: A cue that predicted conflict in an upcoming Eriksen flanker task modulated conflict regulation in a subsequent number Stroop task. In 3 experiments, 1 of which included an exact replication condition, we failed to…

Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

International Nuclear Information System (INIS)

Kanginakudru, Sriramana; DeSmet, Marsha; Thomas, Yanique; Morgan, Iain M.; Androphy, Elliot J.

2015-01-01

The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reduced viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication

Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

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Kanginakudru, Sriramana, E-mail: skangina@iu.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); DeSmet, Marsha, E-mail: mdesmet@iupui.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); Thomas, Yanique, E-mail: ysthomas@umail.iu.edu [Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN (United States); Morgan, Iain M., E-mail: immorgan@vcu.edu [VCU Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, Virginia (United States); Androphy, Elliot J., E-mail: eandro@iu.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN (United States)

2015-04-15

The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reduced viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication.

Different nucleosomal architectures at early and late replicating origins in Saccharomyces cerevisiae.

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Soriano, Ignacio; Morafraile, Esther C; Vázquez, Enrique; Antequera, Francisco; Segurado, Mónica

2014-09-13

Eukaryotic genomes are replicated during S phase according to a temporal program. Several determinants control the timing of origin firing, including the chromatin environment and epigenetic modifications. However, how chromatin structure influences the timing of the activation of specific origins is still poorly understood. By performing high-resolution analysis of genome-wide nucleosome positioning we have identified different chromatin architectures at early and late replication origins. These different patterns are already established in G1 and are tightly correlated with the organization of adjacent transcription units. Moreover, specific early and late nucleosomal patterns are fixed robustly, even in rpd3 mutants in which histone acetylation and origin timing have been significantly altered. Nevertheless, higher histone acetylation levels correlate with the local modulation of chromatin structure, leading to increased origin accessibility. In addition, we conducted parallel analyses of replication and nucleosome dynamics that revealed that chromatin structure at origins is modulated during origin activation. Our results show that early and late replication origins present distinctive nucleosomal configurations, which are preferentially associated to different genomic regions. Our data also reveal that origin structure is dynamic and can be locally modulated by histone deacetylation, as well as by origin activation. These data offer novel insight into the contribution of chromatin structure to origin selection and firing in budding yeast.

Interference of biphotons upon parametric down-conversion in the field of biharmonic pumping

International Nuclear Information System (INIS)

Zolotoverkh, I I

2014-01-01

We report theoretical investigation of interference of biphotons emitted upon type-II collinear parametric down-conversion in the case of biharmonic pumping. Interference occurs when an optical or electronic shutter is used as an amplitude modulator in the experimental scheme. The phase of the interference is shown to depend on the time interval between the instant the shutter is opened and the instant corresponding to the maximum pump intensity. The main parameter affecting the visibility of the interference pattern is a time interval during which the shutter is open. (nonlinear optical phenomena)

Mouse Norovirus infection promotes autophagy induction to facilitate replication but prevents final autophagosome maturation

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O’Donnell, Tanya B. [Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne 3010 (Australia); Hyde, Jennifer L. [School of Chemical and Biological Sciences, University of Queensland, St. Lucia, Brisbane, Queensland 4072 (Australia); Mintern, Justine D. [Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne 3010 (Australia); Mackenzie, Jason M., E-mail: jason.mackenzie@unimelb.edu.au [Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne 3010 (Australia)

2016-05-15

Autophagy is a cellular process used to eliminate intracellular pathogens. Many viruses however are able to manipulate this cellular process for their own advantage. Here we demonstrate that Mouse Norovirus (MNV) infection induces autophagy but does not appear to utilise the autophagosomal membrane for establishment and formation of the viral replication complex. We have observed that MNV infection results in lipidation and recruitment of LC3 to the autophagosome membrane but prevents subsequent fusion of the autophagosomes with lysosomes, as SQSTM1 (an autophagy receptor) accumulates and Lysosome-Associated Membrane Protein1 is sequestered to the MNV replication complex (RC) rather than to autophagosomes. We have additionally observed that chemical modulation of autophagy differentially affects MNV replication. From this study we can conclude that MNV infection induces autophagy, however suppresses the final maturation step of this response, indicating that autophagy induction contributes to MNV replication independently of RC biogenesis. - Highlights: • MNV induces autophagy in infected murine macrophages. • MNV does not utilise autophagosomal membranes for replication. • The MNV-induced autophagosomes do not fuse with lysosomes. • MNV sequesters SQSTM1 to prevent autophagy degradation and turnover. • Chemical modulation of autophagy enhances MNV replication.

Mouse Norovirus infection promotes autophagy induction to facilitate replication but prevents final autophagosome maturation

International Nuclear Information System (INIS)

O’Donnell, Tanya B.; Hyde, Jennifer L.; Mintern, Justine D.; Mackenzie, Jason M.

2016-01-01

Autophagy is a cellular process used to eliminate intracellular pathogens. Many viruses however are able to manipulate this cellular process for their own advantage. Here we demonstrate that Mouse Norovirus (MNV) infection induces autophagy but does not appear to utilise the autophagosomal membrane for establishment and formation of the viral replication complex. We have observed that MNV infection results in lipidation and recruitment of LC3 to the autophagosome membrane but prevents subsequent fusion of the autophagosomes with lysosomes, as SQSTM1 (an autophagy receptor) accumulates and Lysosome-Associated Membrane Protein1 is sequestered to the MNV replication complex (RC) rather than to autophagosomes. We have additionally observed that chemical modulation of autophagy differentially affects MNV replication. From this study we can conclude that MNV infection induces autophagy, however suppresses the final maturation step of this response, indicating that autophagy induction contributes to MNV replication independently of RC biogenesis. - Highlights: • MNV induces autophagy in infected murine macrophages. • MNV does not utilise autophagosomal membranes for replication. • The MNV-induced autophagosomes do not fuse with lysosomes. • MNV sequesters SQSTM1 to prevent autophagy degradation and turnover. • Chemical modulation of autophagy enhances MNV replication.

Systematic identification of novel, essential host genes affecting bromovirus RNA replication.

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Brandi L Gancarz

Full Text Available Positive-strand RNA virus replication involves viral proteins and cellular proteins at nearly every replication step. Brome mosaic virus (BMV is a well-established model for dissecting virus-host interactions and is one of very few viruses whose RNA replication, gene expression and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae. Previously, our laboratory identified ∼100 non-essential host genes whose loss inhibited or enhanced BMV replication at least 3-fold. However, our isolation of additional BMV-modulating host genes by classical genetics and other results underscore that genes essential for cell growth also contribute to BMV RNA replication at a frequency that may be greater than that of non-essential genes. To systematically identify novel, essential host genes affecting BMV RNA replication, we tested a collection of ∼900 yeast strains, each with a single essential gene promoter replaced by a doxycycline-repressible promoter, allowing repression of gene expression by adding doxycycline to the growth medium. Using this strain array of ∼81% of essential yeast genes, we identified 24 essential host genes whose depleted expression reproducibly inhibited or enhanced BMV RNA replication. Relevant host genes are involved in ribosome biosynthesis, cell cycle regulation and protein homeostasis, among other cellular processes. BMV 2a(Pol levels were significantly increased in strains depleted for a heat shock protein (HSF1 or proteasome components (PRE1 and RPT6, suggesting these genes may affect BMV RNA replication by directly or indirectly modulating 2a(Pol localization, post-translational modification or interacting partners. Investigating the diverse functions of these newly identified essential host genes should advance our understanding of BMV-host interactions and normal cellular pathways, and suggest new modes of virus control.

Distinct Contributions of Autophagy Receptors in Measles Virus Replication.

Science.gov (United States)

Petkova, Denitsa S; Verlhac, Pauline; Rozières, Aurore; Baguet, Joël; Claviere, Mathieu; Kretz-Remy, Carole; Mahieux, Renaud; Viret, Christophe; Faure, Mathias

2017-05-22

Autophagy is a potent cell autonomous defense mechanism that engages the lysosomal pathway to fight intracellular pathogens. Several autophagy receptors can recognize invading pathogens in order to target them towards autophagy for their degradation after the fusion of pathogen-containing autophagosomes with lysosomes. However, numerous intracellular pathogens can avoid or exploit autophagy, among which is measles virus (MeV). This virus induces a complete autophagy flux, which is required to improve viral replication. We therefore asked how measles virus interferes with autophagy receptors during the course of infection. We report that in addition to NDP52/CALCOCO₂ and OPTINEURIN/OPTN, another autophagy receptor, namely T6BP/TAXIBP1, also regulates the maturation of autophagosomes by promoting their fusion with lysosomes, independently of any infection. Surprisingly, only two of these receptors, NDP52 and T6BP, impacted measles virus replication, although independently, and possibly through physical interaction with MeV proteins. Thus, our results suggest that a restricted set of autophagosomes is selectively exploited by measles virus to replicate in the course of infection.

A Review on Successive Interference Cancellation-Based Optical PPM-CDMA Signaling

Science.gov (United States)

Alsowaidi, Naif; Eltaif, Tawfig; Mokhtar, Mohd Ridzuan

2017-06-01

This paper presents a comprehensive review of successive interference cancellation (SIC) scheme using pulse position modulation (PPM) for optical code division multiple access (OCDMA) systems. SIC scheme focuses on high-intensity signal, which will be selected after all users were detected, and then it will be subtracted from the overall received signal, hence, generating a new received signal. This process continues till all users eliminated one by one have been detected. It is shown that the random location of the sequences due to PPM encoding can reduce the probability of concentrated buildup of the pulse overlap in any one-slot time, and support SIC to easily remove the effect of the strongest signal at each stage of the cancellation process. The system bit error rate (BER) performance with modified quadratic congruence (MQC) codes used as signature sequence has been investigated. A detailed theoretical analysis of proposed system taking into account the impact of imperfect interference cancellation, the loss produced from the splitting during encoding and decoding, the channel loss and multiple access interference is presented. Results show that under average effective power constraint optical CDMA system using SIC scheme with M-ary PPM modulation outperforms conventional correlator detector and SIC scheme with on-off keying (OOK) modulation.

Levels of Interference in Long and Short-Term Memory Differentially Modulate Non-REM and REM Sleep.

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Fraize, Nicolas; Carponcy, Julien; Joseph, Mickaël Antoine; Comte, Jean-Christophe; Luppi, Pierre-Hervé; Libourel, Paul-Antoine; Salin, Paul-Antoine; Malleret, Gaël; Parmentier, Régis

2016-12-01

It is commonly accepted that sleep is beneficial to memory processes, but it is still unclear if this benefit originates from improved memory consolidation or enhanced information processing. It has thus been proposed that sleep may also promote forgetting of undesirable and non-essential memories, a process required for optimization of cognitive resources. We tested the hypothesis that non-rapid eye movement sleep (NREMS) promotes forgetting of irrelevant information, more specifically when processing information in working memory (WM), while REM sleep (REMS) facilitates the consolidation of important information. We recorded sleep patterns of rats trained in a radial maze in three different tasks engaging either the long-term or short-term storage of information, as well as a gradual level of interference. We observed a transient increase in REMS amount on the day the animal learned the rule of a long-term/reference memory task (RM), and, in contrast, a positive correlation between the performance of rats trained in a WM task involving an important processing of interference and the amount of NREMS or slow wave activity. Various oscillatory events were also differentially modulated by the type of training involved. Notably, NREMS spindles and REMS rapid theta increase with RM training, while sharp-wave ripples increase with all types of training. These results suggest that REMS, but also rapid oscillations occurring during NREMS would be specifically implicated in the long-term memory in RM, whereas NREMS and slow oscillations could be involved in the forgetting of irrelevant information required for WM. © 2016 Associated Professional Sleep Societies, LLC.

Insulated hsp70B' promoter: stringent heat-inducible activity in replication-deficient, but not replication-competent adenoviruses.

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Rohmer, Stanimira; Mainka, Astrid; Knippertz, Ilka; Hesse, Andrea; Nettelbeck, Dirk M

2008-04-01

Key to the realization of gene therapy is the development of efficient and targeted gene transfer vectors. Therapeutic gene transfer by replication-deficient or more recently by conditionally replication-competent/oncolytic adenoviruses has shown much promise. For specific applications, however, it will be advantageous to provide vectors that allow for external control of gene expression. The efficient cellular heat shock system in combination with available technology for focused and controlled hyperthermia suggests heat-regulated transcription control as a promising tool for this purpose. We investigated the feasibility of a short fragment of the human hsp70B' promoter, with and without upstream insulator elements, for the regulation of transgene expression by replication-deficient or oncolytic adenoviruses. Two novel adenoviral vectors with an insulated hsp70B' promoter were developed and showed stringent heat-inducible gene expression with induction ratios up to 8000-fold. In contrast, regulation of gene expression from the hsp70B' promoter without insulation was suboptimal. In replication-competent/oncolytic adenoviruses regulation of the hsp70B' promoter was lost specifically during late replication in permissive cells and could not be restored by the insulators. We developed novel adenovirus gene transfer vectors that feature improved and stringent regulation of transgene expression from the hsp70B' promoter using promoter insulation. These vectors have potential for gene therapy applications that benefit from external modulation of therapeutic gene expression or for combination therapy with hyperthermia. Furthermore, our study reveals that vector replication can deregulate inserted cellular promoters, an observation which is of relevance for the development of replication-competent/oncolytic gene transfer vectors. (c) 2008 John Wiley & Sons, Ltd.

Inhibition of Hepatitis B virus cccDNA replication by siRNA

International Nuclear Information System (INIS)

Li Guiqiu; Gu Hongxi; Li Di; Xu Weizhen

2007-01-01

The development of an effective therapy for Hepatitis B virus (HBV) infection is still a challenge. Progress in RNA interference (RNAi) has shed slight on developing a new anti-HBV strategy. Here, we present a series of experiments showing a significant reduction in HBV transcripts and replication intermediates in HepG2.2.15 cells by vector-based siRNA targeted nuclear localization signal (NLS) region. More importantly, we showed that siRNA1 markedly inhibited HBV covalently closed circular DNA (cccDNA) replication. Our results indicated that HBV NLS may serve as a novel RNAi target to combat HBV infection, which can enhance anti-HBV efficacy and overcome the drawbacks of current therapies

Spatial Landau-Zener-Stueckelberg interference in spinor Bose-Einstein condensates

International Nuclear Information System (INIS)

Zhang, J.-N.; Sun, C.-P.; Yi, S.; Nori, Franco

2011-01-01

We investigate the Stueckelberg oscillations of a spin-1 Bose-Einstein condensate subject to a spatially inhomogeneous transverse magnetic field and a periodic longitudinal field. We show that the time-domain Stueckelberg oscillations result in modulations in the density profiles of all spin components due to the spatial inhomogeneity of the transverse field. This phenomenon represents the Landau-Zener-Stueckelberg interference in the space domain. Since the magnetic dipole-dipole interaction between spin-1 atoms induces an inhomogeneous effective magnetic field, interference fringes also appear if a dipolar spinor condensate is driven periodically. We also point out some potential applications of this spatial Landau-Zener-Stuekelberg interference.

Human ribonuclease H1 resolves R-loops and thereby enables progression of the DNA replication fork.

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Parajuli, Shankar; Teasley, Daniel C; Murali, Bhavna; Jackson, Jessica; Vindigni, Alessandro; Stewart, Sheila A

2017-09-15

Faithful DNA replication is essential for genome stability. To ensure accurate replication, numerous complex and redundant replication and repair mechanisms function in tandem with the core replication proteins to ensure DNA replication continues even when replication challenges are present that could impede progression of the replication fork. A unique topological challenge to the replication machinery is posed by RNA-DNA hybrids, commonly referred to as R-loops. Although R-loops play important roles in gene expression and recombination at immunoglobulin sites, their persistence is thought to interfere with DNA replication by slowing or impeding replication fork progression. Therefore, it is of interest to identify DNA-associated enzymes that help resolve replication-impeding R-loops. Here, using DNA fiber analysis, we demonstrate that human ribonuclease H1 (RNH1) plays an important role in replication fork movement in the mammalian nucleus by resolving R-loops. We found that RNH1 depletion results in accumulation of RNA-DNA hybrids, slowing of replication forks, and increased DNA damage. Our data uncovered a role for RNH1 in global DNA replication in the mammalian nucleus. Because accumulation of RNA-DNA hybrids is linked to various human cancers and neurodegenerative disorders, our study raises the possibility that replication fork progression might be impeded, adding to increased genomic instability and contributing to disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Local-global interference is modulated by age, sex and anterior corpus callosum size.

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Müller-Oehring, Eva M; Schulte, Tilman; Raassi, Carla; Pfefferbaum, Adolf; Sullivan, Edith V

2007-04-20

To identify attentional and neural mechanisms affecting global and local feature extraction, we devised a global-local hierarchical letter paradigm to test the hypothesis that aging reduces functional cerebral lateralization through corpus callosum (CC) degradation. Participants (37 men and women, 26-79 years) performed a task requiring global, local, or global+local attention and underwent structural MRI for CC measurement. Although reaction time (RT) slowed with age, all participants had faster RTs to local than global targets. This local precedence effect together with greater interference from incongruent local information and greater response conflict from local targets each correlated with older age and smaller callosal genu (anterior) areas. These findings support the hypothesis that the CC mediates lateralized local-global processes by inhibition of task-irrelevant information under selective attention conditions. Further, with advancing age smaller genu size leads to less robust inhibition, thereby reducing cerebral lateralization and permitting interference to influence processing. Sex was an additional modifier of interference, in that callosum-interference relationships were evident in women but not in men. Regardless of age, smaller splenium (posterior) areas correlated with less response facilitation from repetition priming of global targets in men, but with greater response facilitation from repetition priming of local targets in women. Our data indicate the following dissociation: anterior callosal structure was associated with inhibitory processes (i.e., interference from incongruency and response conflict), which are vulnerable to the effects of age and sex, whereas posterior callosal structure was associated with facilitation processes from repetition priming dependent on sex and independent of age.

Effects of context on visuomotor interference depends on the perspective of observed actions.

Directory of Open Access Journals (Sweden)

Marta Bortoletto

Full Text Available Visuomotor interference occurs when the execution of an action is facilitated by the concurrent observation of the same action and hindered by the concurrent observation of a different action. There is evidence that visuomotor interference can be modulated top-down by higher cognitive functions, depending on whether own performed actions or observed actions are selectively attended. Here, we studied whether these effects of cognitive context on visuomotor interference are also dependent on the point-of-view of the observed action. We employed a delayed go/no-go task known to induce visuomotor interference. Static images of hand gestures in either egocentric or allocentric perspective were presented as "go" stimuli after participants were pre-cued to prepare either a matching (congruent or non-matching (incongruent action. Participants performed this task in two different cognitive contexts: In one, they focused on the visual image of the hand gesture shown as the go stimulus (image context, whereas in the other they focused on the hand gesture they performed (action context. We analyzed reaction times to initiate the prepared action upon presentation of the gesture image and found evidence of visuomotor interference in both contexts and for both perspectives. Strikingly, results show that the effect of cognitive context on visuomotor interference also depends on the perspective of observed actions. When focusing on own-actions, visuomotor interference was significantly less for gesture images in allocentric perspective than in egocentric perspective; when focusing on observed actions, visuomotor interference was present regardless of the perspective of the gesture image. Overall these data suggest that visuomotor interference may be modulated by higher cognitive processes, so that when we are specifically attending to our own actions, images depicting others' actions (allocentric perspective have much less interference on our own actions.

MicroRNA regulation of human protease genes essential for influenza virus replication.

Directory of Open Access Journals (Sweden)

Victoria A Meliopoulos

Full Text Available Influenza A virus causes seasonal epidemics and periodic pandemics threatening the health of millions of people each year. Vaccination is an effective strategy for reducing morbidity and mortality, and in the absence of drug resistance, the efficacy of chemoprophylaxis is comparable to that of vaccines. However, the rapid emergence of drug resistance has emphasized the need for new drug targets. Knowledge of the host cell components required for influenza replication has been an area targeted for disease intervention. In this study, the human protease genes required for influenza virus replication were determined and validated using RNA interference approaches. The genes validated as critical for influenza virus replication were ADAMTS7, CPE, DPP3, MST1, and PRSS12, and pathway analysis showed these genes were in global host cell pathways governing inflammation (NF-κB, cAMP/calcium signaling (CRE/CREB, and apoptosis. Analyses of host microRNAs predicted to govern expression of these genes showed that eight miRNAs regulated gene expression during virus replication. These findings identify unique host genes and microRNAs important for influenza replication providing potential new targets for disease intervention strategies.

MicroRNA regulation of human protease genes essential for influenza virus replication.

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Meliopoulos, Victoria A; Andersen, Lauren E; Brooks, Paula; Yan, Xiuzhen; Bakre, Abhijeet; Coleman, J Keegan; Tompkins, S Mark; Tripp, Ralph A

2012-01-01

Influenza A virus causes seasonal epidemics and periodic pandemics threatening the health of millions of people each year. Vaccination is an effective strategy for reducing morbidity and mortality, and in the absence of drug resistance, the efficacy of chemoprophylaxis is comparable to that of vaccines. However, the rapid emergence of drug resistance has emphasized the need for new drug targets. Knowledge of the host cell components required for influenza replication has been an area targeted for disease intervention. In this study, the human protease genes required for influenza virus replication were determined and validated using RNA interference approaches. The genes validated as critical for influenza virus replication were ADAMTS7, CPE, DPP3, MST1, and PRSS12, and pathway analysis showed these genes were in global host cell pathways governing inflammation (NF-κB), cAMP/calcium signaling (CRE/CREB), and apoptosis. Analyses of host microRNAs predicted to govern expression of these genes showed that eight miRNAs regulated gene expression during virus replication. These findings identify unique host genes and microRNAs important for influenza replication providing potential new targets for disease intervention strategies.

Infection of Mosquito Cells (C6/36) by Dengue-2 Virus Interferes with Subsequent Infection by Yellow Fever Virus.

Science.gov (United States)

Abrao, Emiliana Pereira; da Fonseca, Benedito Antônio Lopes

2016-02-01

Dengue is one of the most important diseases caused by arboviruses in the world. Yellow fever is another arthropod-borne disease of great importance to public health that is endemic to tropical regions of Africa and the Americas. Both yellow fever and dengue viruses are flaviviruses transmitted by Aedes aegypti mosquitoes, and then, it is reasonable to consider that in a given moment, mosquito cells could be coinfected by both viruses. Therefore, we decided to evaluate if sequential infections of dengue and yellow fever viruses (and vice-versa) in mosquito cells could affect the virus replication patterns. Using immunofluorescence and real-time PCR-based replication assays in Aedes albopictus C6/36 cells with single or sequential infections with both viruses, we demonstrated the occurrence of viral interference, also called superinfection exclusion, between these two viruses. Our results show that this interference pattern is particularly evident when cells were first infected with dengue virus and subsequently with yellow fever virus (YFV). Reduction in dengue virus replication, although to a lower extent, was also observed when C6/36 cells were initially infected with YFV followed by dengue virus infection. Although the importance that these findings have on nature is unknown, this study provides evidence, at the cellular level, of the occurrence of replication interference between dengue and yellow fever viruses and raises the question if superinfection exclusion could be a possible explanation, at least partially, for the reported lack of urban yellow fever occurrence in regions where a high level of dengue transmission occurs.

Unraveling cell processes: interference imaging interwoven with data analysis

DEFF Research Database (Denmark)

Brazhe, Nadezda; Brazhe, Alexey; Pavlov, A N

2006-01-01

The paper presents results on the application of interference microscopy and wavelet-analysis for cell visualization and studies of cell dynamics. We demonstrate that interference imaging of erythrocytes can reveal reorganization of the cytoskeleton and inhomogenity in the distribution of hemoglo......The paper presents results on the application of interference microscopy and wavelet-analysis for cell visualization and studies of cell dynamics. We demonstrate that interference imaging of erythrocytes can reveal reorganization of the cytoskeleton and inhomogenity in the distribution...... properties differ from cell type to cell type and depend on the cellular compartment. Our results suggest that low frequency variations (0.1-0.6 Hz) result from plasma membrane processes and that higher frequency variations (20-26 Hz) are related to the movement of vesicles. Using double-wavelet analysis, we...... study the modulation of the 1 Hz rhythm in neurons and reveal its changes under depolarization and hyperpolarization of the plasma membrane. We conclude that interference microscopy combined with wavelet analysis is a useful technique for non-invasive cell studies, cell visualization, and investigation...

Localizing semantic interference from distractor sounds in picture naming: A dual-task study.

Science.gov (United States)

Mädebach, Andreas; Kieseler, Marie-Luise; Jescheniak, Jörg D

2017-10-13

In this study we explored the locus of semantic interference in a novel picture-sound interference task in which participants name pictures while ignoring environmental distractor sounds. In a previous study using this task (Mädebach, Wöhner, Kieseler, & Jescheniak, in Journal of Experimental Psychology: Human Perception and Performance, 43, 1629-1646, 2017), we showed that semantically related distractor sounds (e.g., BARKING dog ) interfere with a picture-naming response (e.g., "horse") more strongly than unrelated distractor sounds do (e.g., DRUMMING drum ). In the experiment reported here, we employed the psychological refractory period (PRP) approach to explore the locus of this effect. We combined a geometric form classification task (square vs. circle; Task 1) with the picture-sound interference task (Task 2). The stimulus onset asynchrony (SOA) between the tasks was systematically varied (0 vs. 500 ms). There were three central findings. First, the semantic interference effect from distractor sounds was replicated. Second, picture naming (in Task 2) was slower with the short than with the long task SOA. Third, both effects were additive-that is, the semantic interference effects were of similar magnitude at both task SOAs. This suggests that the interference arises during response selection or later stages, not during early perceptual processing. This finding corroborates the theory that semantic interference from distractor sounds reflects a competitive selection mechanism in word production.

BPIFB6 Regulates Secretory Pathway Trafficking and Enterovirus Replication.

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Morosky, Stefanie; Lennemann, Nicholas J; Coyne, Carolyn B

2016-05-15

Bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) is an endoplasmic reticulum (ER)-localized host factor that negatively regulates coxsackievirus B (CVB) replication through its control of the autophagic pathway. Here, we show that another member of the BPIFB family, BPIFB6, functions as a positive regulator of CVB, and other enterovirus, replication by controlling secretory pathway trafficking and Golgi complex morphology. We show that similar to BPIFB3, BPIFB6 localizes exclusively to the ER, where it associates with other members of the BPIFB family. However, in contrast to our findings that RNA interference (RNAi)-mediated silencing of BPIFB3 greatly enhances CVB replication, we show that silencing of BPIFB6 expression dramatically suppresses enterovirus replication in a pan-viral manner. Mechanistically, we show that loss of BPIFB6 expression induces pronounced alterations in retrograde and anterograde trafficking, which correlate with dramatic fragmentation of the Golgi complex. Taken together, these data implicate BPIFB6 as a key regulator of secretory pathway trafficking and viral replication and suggest that members of the BPIFB family participate in diverse host cell functions to regulate virus infections. Enterovirus infections are associated with a number of severe pathologies, such as aseptic meningitis, dilated cardiomyopathy, type I diabetes, paralysis, and even death. These viruses, which include coxsackievirus B (CVB), poliovirus (PV), and enterovirus 71 (EV71), co-opt the host cell secretory pathway, which controls the transport of proteins from the endoplasmic reticulum to the Golgi complex, to facilitate their replication. Here we report on the identification of a novel regulator of the secretory pathway, bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 6 (BPIFB6), whose expression is required for enterovirus replication. We show that loss of BPIFB6 expression

BPIFB6 Regulates Secretory Pathway Trafficking and Enterovirus Replication

Science.gov (United States)

Morosky, Stefanie; Lennemann, Nicholas J.

2016-01-01

ABSTRACT Bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) is an endoplasmic reticulum (ER)-localized host factor that negatively regulates coxsackievirus B (CVB) replication through its control of the autophagic pathway. Here, we show that another member of the BPIFB family, BPIFB6, functions as a positive regulator of CVB, and other enterovirus, replication by controlling secretory pathway trafficking and Golgi complex morphology. We show that similar to BPIFB3, BPIFB6 localizes exclusively to the ER, where it associates with other members of the BPIFB family. However, in contrast to our findings that RNA interference (RNAi)-mediated silencing of BPIFB3 greatly enhances CVB replication, we show that silencing of BPIFB6 expression dramatically suppresses enterovirus replication in a pan-viral manner. Mechanistically, we show that loss of BPIFB6 expression induces pronounced alterations in retrograde and anterograde trafficking, which correlate with dramatic fragmentation of the Golgi complex. Taken together, these data implicate BPIFB6 as a key regulator of secretory pathway trafficking and viral replication and suggest that members of the BPIFB family participate in diverse host cell functions to regulate virus infections. IMPORTANCE Enterovirus infections are associated with a number of severe pathologies, such as aseptic meningitis, dilated cardiomyopathy, type I diabetes, paralysis, and even death. These viruses, which include coxsackievirus B (CVB), poliovirus (PV), and enterovirus 71 (EV71), co-opt the host cell secretory pathway, which controls the transport of proteins from the endoplasmic reticulum to the Golgi complex, to facilitate their replication. Here we report on the identification of a novel regulator of the secretory pathway, bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 6 (BPIFB6), whose expression is required for enterovirus replication. We show that loss of

Interference Robust Transmission for the Downlink of an OFDM-Based Mobile Communications System

Directory of Open Access Journals (Sweden)

Markus Konrad

2008-01-01

Full Text Available Radio networks for future mobile communications systems, for example, 3GPP Long-Term Evolution (LTE, are likely to use an orthogonal frequency division multiplexing- (OFDM- based air interface in the downlink with a frequency reuse factor of one to avoid frequency planning. Therefore, system capacity is limited by interference, which is particularly crucial for mobile terminals with a single receive antenna. Nevertheless, next generation mobile communications systems aim at increasing downlink throughput. In this paper, a single antenna interference cancellation (SAIC algorithm is introduced for amplitude-shift keying (ASK modulation schemes in combination with bit-interleaved coded OFDM. By using such a transmission strategy, high gains in comparison to a conventional OFDM transmission with quadrature amplitude modulation (QAM can be achieved. The superior performance of the novel scheme is confirmed by an analytical bit-error probability (BEP analysis of the SAIC receiver for a single interferer, Rayleigh fading, and uncoded transmission. For the practically more relevant multiple interferer case we present an adaptive least-mean-square (LMS and an adaptive recursive least-squares (RLS SAIC algorithm. We show that in particular the RLS approach enables a good tradeoff between performance and complexity and is robust even to multiple interferers.

Brief Meditation and the Interaction between Emotional Interference and Anxiety

Directory of Open Access Journals (Sweden)

Carolina Baptista Menezes

Full Text Available ABSTRACT This pilot study assessed the effects of a five day focused meditation training on the interplay between emotional interference and anxiety in a non clinical sample randomized into two groups (experimental=13; control=18. Emotional interference was indexed comparing the reaction times in an attention span task with negative or neutral distracting images. Anxiety experienced during the task was also assessed through self-report. Only in the control group higher anxiety levels interacted with greater emotional interference and a worse evaluation of valence and arousal of emotional images. These preliminary findings suggest that meditation may help modulating anxiety effects on bias to negative stimuli, and that even a short training may facilitate self-regulatory processes.

Self-interference digital holography with a geometric-phase hologram lens.

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Choi, KiHong; Yim, Junkyu; Yoo, Seunghwi; Min, Sung-Wook

2017-10-01

Self-interference digital holography (SIDH) is actively studied because the hologram acquisition under the incoherent illumination condition is available. The key component in this system is wavefront modulating optics, which modulates an incoming object wave into two different wavefront curvatures. In this Letter, the geometric-phase hologram lens is introduced in the SIDH system to perform as a polarization-sensitive wavefront modulator and a single-path beam splitter. This special optics has several features, such as high transparency, a modulation efficiency up to 99%, a thinness of a few millimeters, and a flat structure. The demonstration system is devised, and the numerical reconstruction results from an acquired complex hologram are presented.

Mechanism of Archaeal MCM Helicase Recruitment to DNA Replication Origins

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Samson, Rachel Y.; Abeyrathne, Priyanka D.; Bell, Stephen D.

2015-01-01

Summary Cellular DNA replication origins direct the recruitment of replicative helicases via the action of initiator proteins belonging to the AAA+ superfamily of ATPases. Archaea have a simplified subset of the eukaryotic DNA replication machinery proteins and possess initiators that appear ancestral to both eukaryotic Orc1 and Cdc6. We have reconstituted origin-dependent recruitment of the homohexameric archaeal MCM in vitro with purified recombinant proteins. Using this system, we reveal that archaeal Orc1-1 fulfills both Orc1 and Cdc6 functions by binding to a replication origin and directly recruiting MCM helicase. We identify the interaction interface between these proteins and reveal how ATP binding by Orc1-1 modulates recruitment of MCM. Additionally, we provide evidence that an open-ring form of the archaeal MCM homohexamer is loaded at origins. PMID:26725007

RNA interference-mediated intrinsic antiviral immunity in invertebrates.

Science.gov (United States)

Nayak, Arabinda; Tassetto, Michel; Kunitomi, Mark; Andino, Raul

2013-01-01

In invertebrates such as insects and nematodes, RNA interference (RNAi) provides RNA-based protection against viruses. This form of immunity restricts viral replication and dissemination from infected cells and viruses, in turn, have evolved evasion mechanisms or RNAi suppressors to counteract host defenses. Recent advances indicate that, in addition to RNAi, other related small RNA pathways contribute to antiviral functions in invertebrates. This has led to a deeper understanding of fundamental aspects of small RNA-based antiviral immunity in invertebrates and its contribution to viral spread and pathogenesis.

The yeast replicative aging model.

Science.gov (United States)

He, Chong; Zhou, Chuankai; Kennedy, Brian K

2018-03-08

It has been nearly three decades since the budding yeast Saccharomyces cerevisiae became a significant model organism for aging research and it has emerged as both simple and powerful. The replicative aging assay, which interrogates the number of times a "mother" cell can divide and produce "daughters", has been a stalwart in these studies, and genetic approaches have led to the identification of hundreds of genes impacting lifespan. More recently, cell biological and biochemical approaches have been developed to determine how cellular processes become altered with age. Together, the tools are in place to develop a holistic view of aging in this single-celled organism. Here, we summarize the current state of understanding of yeast replicative aging with a focus on the recent studies that shed new light on how aging pathways interact to modulate lifespan in yeast. Copyright © 2018. Published by Elsevier B.V.

Optical bistability via quantum interference from incoherent pumping and spontaneous emission

International Nuclear Information System (INIS)

Sahrai, M.; Asadpour, S.H.; Sadighi-Bonabi, R.

2011-01-01

We theoretically investigate the optical bistability (OB) in a V-type three-level atomic system confined in a unidirectional ring cavity via incoherent pumping field. It is shown that the threshold of optical bistability can be controlled by the rate of an incoherent pumping field and by interference mechanism arising from the spontaneous emission and incoherent pumping field. We demonstrate that the optical bistability converts to optical multi-stability (OM) by the quantum interference mechanism. - Highlights: → We modulate the optical bistability (OB) in a four-level N-type atomic system. → The threshold of optical bistability can be controlled by the quantum interferences. → OB converts to optical multi-stability (OM) by the quantum interferences. → We discuss the effect of an incoherent pumping field on reduction of OB threshold.

PRMT5 restricts hepatitis B virus replication through epigenetic repression of covalently closed circular DNA transcription and interference with pregenomic RNA encapsidation.

Science.gov (United States)

Zhang, Wen; Chen, Jieliang; Wu, Min; Zhang, Xiaonan; Zhang, Min; Yue, Lei; Li, Yaming; Liu, Jiangxia; Li, Baocun; Shen, Fang; Wang, Yang; Bai, Lu; Protzer, Ulrike; Levrero, Massimo; Yuan, Zhenghong

2017-08-01

Chronic hepatitis B virus (HBV) infection remains a major health problem worldwide. The covalently closed circular DNA (cccDNA) minichromosome, which serves as the template for the transcription of viral RNAs, plays a key role in viral persistence. While accumulating evidence suggests that cccDNA transcription is regulated by epigenetic machinery, particularly the acetylation of cccDNA-bound histone 3 (H3) and H4, the potential contributions of histone methylation and related host factors remain obscure. Here, by screening a series of methyltransferases and demethylases, we identified protein arginine methyltransferase 5 (PRMT5) as an effective restrictor of HBV transcription and replication. In cell culture-based models for HBV infection and in liver tissues of patients with chronic HBV infection, we found that symmetric dimethylation of arginine 3 on H4 on cccDNA was a repressive marker of cccDNA transcription and was regulated by PRMT5 depending on its methyltransferase domain. Moreover, PRMT5-triggered symmetric dimethylation of arginine 3 on H4 on the cccDNA minichromosome involved an interaction with the HBV core protein and the Brg1-based human SWI/SNF chromatin remodeler, which resulted in down-regulation of the binding of RNA polymerase II to cccDNA. In addition to the inhibitory effect on cccDNA transcription, PRMT5 inhibited HBV core particle DNA production independently of its methyltransferase activity. Further study revealed that PRMT5 interfered with pregenomic RNA encapsidation by preventing its interaction with viral polymerase protein through binding to the reverse transcriptase-ribonuclease H region of polymerase, which is crucial for the polymerase-pregenomic RNA interaction. PRMT5 restricts HBV replication through a two-part mechanism including epigenetic suppression of cccDNA transcription and interference with pregenomic RNA encapsidation; these findings improve the understanding of epigenetic regulation of HBV transcription and host

An inter-lighting interference cancellation scheme for MISO-VLC systems

Science.gov (United States)

Kim, Kyuntak; Lee, Kyujin; Lee, Kyesan

2017-08-01

In this paper, we propose an inter-lighting interference cancellation (ILIC) scheme to reduce the interference between adjacent light-emitting diodes (LEDs) and enhance the transmission capacity of multiple-input-single-output (MISO)-visible light communication (VLC) systems. In indoor environments, multiple LEDs have normally been used as lighting sources, allowing the design of MISO-VLC systems. To enhance the transmission capacity, different data should be simultaneously transmitted from each LED; however, that can lead to interference between adjacent LEDs. In that case, relatively low-received power signals are subjected to large interference because wireless optical systems generally use intensity modulation and direct detection. Thus, only the signal with the highest received power can be detected, while the other received signals cannot be detected. To solve this problem, we propose the ILIC scheme for MISO-VLC systems. The proposed scheme preferentially detects the highest received power signal, and this signal is referred as interference signal by an interference component generator. Then, relatively low-received power signal can be detected by cancelling the interference signal from the total received signals. Therefore, the performance of the proposed scheme can improve the total average bit error rate and throughput of a MISO-VLC system.

Interference-mediated synaptonemal complex formation with embedded crossover designation

Science.gov (United States)

Zhang, Liangran; Espagne, Eric; de Muyt, Arnaud; Zickler, Denise; Kleckner, Nancy E.

2014-01-01

Biological systems exhibit complex patterns at length scales ranging from the molecular to the organismic. Along chromosomes, events often occur stochastically at different positions in different nuclei but nonetheless tend to be relatively evenly spaced. Examples include replication origin firings, formation of chromatin loops along chromosome axes and, during meiosis, localization of crossover recombination sites (“crossover interference”). We present evidence in the fungus Sordaria macrospora that crossover interference is part of a broader pattern that includes synaptonemal complex (SC) nucleation. This pattern comprises relatively evenly spaced SC nucleation sites, among which a subset are crossover sites that show a classical interference distribution. This pattern ensures that SC forms regularly along the entire length of the chromosome as required for the maintenance of homolog pairing while concomitantly having crossover interactions locally embedded within the SC structure as required for both DNA recombination and structural events of chiasma formation. This pattern can be explained by a threshold-based designation and spreading interference process. This model can be generalized to give diverse types of related and/or partially overlapping patterns, in two or more dimensions, for any type of object. PMID:25380597

Hepatitis C Virus Replication Depends on Endosomal Cholesterol Homeostasis.

Science.gov (United States)

Stoeck, Ina Karen; Lee, Ji-Young; Tabata, Keisuke; Romero-Brey, Inés; Paul, David; Schult, Philipp; Lohmann, Volker; Kaderali, Lars; Bartenschlager, Ralf

2018-01-01

Similar to other positive-strand RNA viruses, hepatitis C virus (HCV) causes massive rearrangements of intracellular membranes, resulting in a membranous web (MW) composed of predominantly double-membrane vesicles (DMVs), the presumed sites of RNA replication. DMVs are enriched for cholesterol, but mechanistic details on the source and recruitment of cholesterol to the viral replication organelle are only partially known. Here we focused on selected lipid transfer proteins implicated in direct lipid transfer at various endoplasmic reticulum (ER)-membrane contact sites. RNA interference (RNAi)-mediated knockdown identified several hitherto unknown HCV dependency factors, such as steroidogenic acute regulatory protein-related lipid transfer domain protein 3 (STARD3), oxysterol-binding protein-related protein 1A and -B (OSBPL1A and -B), and Niemann-Pick-type C1 (NPC1), all residing at late endosome and lysosome membranes and required for efficient HCV RNA replication but not for replication of the closely related dengue virus. Focusing on NPC1, we found that knockdown or pharmacological inhibition caused cholesterol entrapment in lysosomal vesicles concomitant with decreased cholesterol abundance at sites containing the viral replicase factor NS5A. In untreated HCV-infected cells, unesterified cholesterol accumulated at the perinuclear region, partially colocalizing with NS5A at DMVs, arguing for NPC1-mediated endosomal cholesterol transport to the viral replication organelle. Consistent with cholesterol being an important structural component of DMVs, reducing NPC1-dependent endosomal cholesterol transport impaired MW integrity. This suggests that HCV usurps lipid transfer proteins, such as NPC1, at ER-late endosome/lysosome membrane contact sites to recruit cholesterol to the viral replication organelle, where it contributes to MW functionality. IMPORTANCE A key feature of the replication of positive-strand RNA viruses is the rearrangement of the host cell

Modulation of the Pyrococcus abyssi NucS endonuclease activity by replication clamp at functional and structural levels.

Science.gov (United States)

Creze, Christophe; Ligabue, Alessio; Laurent, Sébastien; Lestini, Roxane; Laptenok, Sergey P; Khun, Joelle; Vos, Marten H; Czjzek, Mirjam; Myllykallio, Hannu; Flament, Didier

2012-05-04

Pyrococcus abyssi NucS is the founding member of a new family of structure-specific DNA endonucleases that interact with the replication clamp proliferating cell nuclear antigen (PCNA). Using a combination of small angle x-ray scattering and surface plasmon resonance analyses, we demonstrate the formation of a stable complex in solution, in which one molecule of the PabNucS homodimer binds to the outside surface of the PabPCNA homotrimer. Using fluorescent labels, PCNA is shown to increase the binding affinity of NucS toward single-strand/double-strand junctions on 5' and 3' flaps, as well as to modulate the cleavage specificity on the branched DNA structures. Our results indicate that the presence of a single major contact between the PabNucS and PabPCNA proteins, together with the complex-induced DNA bending, facilitate conformational flexibility required for specific cleavage at the single-strand/double-strand DNA junction.

Modulation of the Pyrococcus abyssi NucS Endonuclease Activity by Replication Clamp at Functional and Structural Levels*

Science.gov (United States)

Creze, Christophe; Ligabue, Alessio; Laurent, Sébastien; Lestini, Roxane; Laptenok, Sergey P.; Khun, Joelle; Vos, Marten H.; Czjzek, Mirjam; Myllykallio, Hannu; Flament, Didier

2012-01-01

Pyrococcus abyssi NucS is the founding member of a new family of structure-specific DNA endonucleases that interact with the replication clamp proliferating cell nuclear antigen (PCNA). Using a combination of small angle x-ray scattering and surface plasmon resonance analyses, we demonstrate the formation of a stable complex in solution, in which one molecule of the PabNucS homodimer binds to the outside surface of the PabPCNA homotrimer. Using fluorescent labels, PCNA is shown to increase the binding affinity of NucS toward single-strand/double-strand junctions on 5′ and 3′ flaps, as well as to modulate the cleavage specificity on the branched DNA structures. Our results indicate that the presence of a single major contact between the PabNucS and PabPCNA proteins, together with the complex-induced DNA bending, facilitate conformational flexibility required for specific cleavage at the single-strand/double-strand DNA junction. PMID:22431731

Phase matching of high order harmonic generation using dynamic phase modulation caused by a non-collinear modulation pulse

Science.gov (United States)

Cohen, Oren; Kapteyn, Henry C.; Mumane, Margaret M.

2010-02-16

Phase matching high harmonic generation (HHG) uses a single, long duration non-collinear modulating pulse intersecting the driving pulse. A femtosecond driving pulse is focused into an HHG medium (such as a noble gas) to cause high-harmonic generation (HHG), for example in the X-ray region of the spectrum, via electrons separating from and recombining with gas atoms. A non-collinear pulse intersects the driving pulse within the gas, and modulates the field seen by the electrons while separated from their atoms. The modulating pulse is low power and long duration, and its frequency and amplitude is chosen to improve HHG phase matching by increasing the areas of constructive interference between the driving pulse and the HHG, relative to the areas of destructive interference.

Non-Invasive Study of Nerve Fibres using Laser Interference Microscopy

DEFF Research Database (Denmark)

Brazhe, A. R.; Brazhe, N. A.; Rodionova, N. N.

2008-01-01

This paper presents the results of a laser interference microscopy study of the morphology and dynamical properties of myelinated nerve fibres. We describe the principles of operation of the phase-modulated laser interference microscope and show how this novel technique allows us to obtain...... information non-invasively about the internal structure of different regions of a nerve fibre. We also analyse the temporal variations in the internal optical properties in order to detect the rhythmic activity in the nerve fibre at different time scales and to shed light on the underlying biological...

Stop feeling: Inhibition of emotional interference following stop-signal trials

OpenAIRE

Eyal eKalanthroff; Noga eCohen; Avishai eHenik

2013-01-01

Although a great deal of literature has been dedicated to the mutual links between emotion and the selective attention component of executive control, there is very little data regarding the links between emotion and the inhibitory component of executive control. In the current study we employed an emotional stop-signal task in order to examine whether emotion modulates and is modulated by inhibitory control. Results replicated previous findings showing reduced inhibitory control [longer stop...

Interference lithography for optical devices and coatings

Science.gov (United States)

Juhl, Abigail Therese

Interference lithography can create large-area, defect-free nanostructures with unique optical properties. In this thesis, interference lithography will be utilized to create photonic crystals for functional devices or coatings. For instance, typical lithographic processing techniques were used to create 1, 2 and 3 dimensional photonic crystals in SU8 photoresist. These structures were in-filled with birefringent liquid crystal to make active devices, and the orientation of the liquid crystal directors within the SU8 matrix was studied. Most of this thesis will be focused on utilizing polymerization induced phase separation as a single-step method for fabrication by interference lithography. For example, layered polymer/nanoparticle composites have been created through the one-step two-beam interference lithographic exposure of a dispersion of 25 and 50 nm silica particles within a photopolymerizable mixture at a wavelength of 532 nm. In the areas of constructive interference, the monomer begins to polymerize via a free-radical process and concurrently the nanoparticles move into the regions of destructive interference. The holographic exposure of the particles within the monomer resin offers a single-step method to anisotropically structure the nanoconstituents within a composite. A one-step holographic exposure was also used to fabricate self-healing coatings that use water from the environment to catalyze polymerization. Polymerization induced phase separation was used to sequester an isocyanate monomer within an acrylate matrix. Due to the periodic modulation of the index of refraction between the monomer and polymer, the coating can reflect a desired wavelength, allowing for tunable coloration. When the coating is scratched, polymerization of the liquid isocyanate is catalyzed by moisture in air; if the indices of the two polymers are matched, the coatings turn transparent after healing. Interference lithography offers a method of creating multifunctional self

Retinoid X Receptor α-Dependent HBV Minichromosome Remodeling and Viral Replication.

Science.gov (United States)

Zhang, Yan; He, Song; Guo, Jin-Jun; Peng, Hong; Fan, Jia-Hao; Li, Qing-Ling

2017-01-01

The HBV covalently closed circular DNA (cccDNA) is organized into a minichromosome in the nuclei of infected hepatocytes through interactions with histone and nonhistone proteins. Retinoid X receptor α (RXRα), a liver-enriched nuclear receptor, participates in regulation of HBV replication and transcription through modulation of HBV enhancer 1 and core promoter activity. This study investigated RXRα involvement in HBV cccDNA epigenetic modifications. Quantitative cccDNA chromatin immunoprecipitation (ChIP) was applied to study the recruitment of RXRα, histones, and chromatin-modifying enzymes to HBV minichromosome in HepG2 cells after transfection of the linear HBV genome. RXRα Was found to directly bind to HBV cccDNA; recruitment of RXRα to HBV mini-chromosome paralleled HBV replication, histone recruitment, and histone acetylation in HBVcccDNA. Moreover, RXRα overexpression or knock-down significantly increased or impaired the recruitment of the p300 acetyltransferase to cccDNAminichromosome. Our results confirmed the regulation of RXRα on HBV replication in vitro and demonstrated the modulation of RXRα on HBV cccDNA epigenetics. These findings provide a profound theoretical and experimental basis for late-model antiviral treatment acting on the HBV cccDNA and minichromosome.

Satellite interference analysis and simulation using personal computers

Science.gov (United States)

Kantak, Anil

1988-03-01

This report presents the complete analysis and formulas necessary to quantify the interference experienced by a generic satellite communications receiving station due to an interfering satellite. Both satellites, the desired as well as the interfering satellite, are considered to be in elliptical orbits. Formulas are developed for the satellite look angles and the satellite transmit angles generally related to the land mask of the receiving station site for both satellites. Formulas for considering Doppler effect due to the satellite motion as well as the Earth's rotation are developed. The effect of the interfering-satellite signal modulation and the Doppler effect on the power received are considered. The statistical formulation of the interference effect is presented in the form of a histogram of the interference to the desired signal power ratio. Finally, a computer program suitable for microcomputers such as IBM AT is provided with the flowchart, a sample run, results of the run, and the program code.

[Research of dual-photoelastic-modulator-based beat frequency modulation and Fourier-Bessel transform imaging spectrometer].

Science.gov (United States)

Wang, Zhi-Bin; Zhang, Rui; Wang, Yao-Li; Huang, Yan-Fei; Chen, You-Hua; Wang, Li-Fu; Yang, Qiang

2014-02-01

As the existing photoelastic-modulator(PEM) modulating frequency in the tens of kHz to hundreds of kHz between, leading to frequency of modulated interference signal is higher, so ordinary array detector cannot effectively caprure interference signal..A new beat frequency modulation method based on dual-photoelastic-modulator (Dual-PEM) and Fourier-Bessel transform is proposed as an key component of dual-photoelastic-modulator-based imaging spectrometer (Dual-PEM-IS) combined with charge coupled device (CCD). The dual-PEM are operated as an electro-optic circular retardance modulator, Operating the PEMs at slightly different resonant frequencies w1 and w2 respectively, generates a differential signal at a much lower heterodyne frequency that modulates the incident light. This method not only retains the advantages of the existing PEM, but also the frequency of modulated photocurrent decreased by 2-3 orders of magnitude (10-500 Hz) and can be detected by common array detector, and the incident light spectra can be obtained by Fourier-Bessel transform of low frequency component in the modulated signal. The method makes the PEM has the dual capability of imaging and spectral measurement. The basic principle is introduced, the basic equations is derived, and the feasibility is verified through the corresponding numerical simulation and experiment. This method has' potential applications in imaging spectrometer technology, and analysis of the effect of deviation of the optical path difference. This work provides the necessary theoretical basis for remote sensing of new Dual-PEM-IS and for engineering implementation of spectra inversion.

Immune modulation through RNA interference-mediated silencing of CD40 in dendritic cells.

Science.gov (United States)

Karimi, Mohammad Hossein; Ebadi, Padideh; Pourfathollah, Ali Akbar; Soheili, Zahra Soheila; Samiee, Shahram; Ataee, Zahra; Tabei, Seyyed Ziyaoddin; Moazzeni, Seyed Mohammad

2009-01-01

RNA interference (RNAi) is an exciting mechanism for knocking down any target gene in transcriptional level. It is now clear that small interfering RNA (siRNA), a 19-21nt long dsRNA, can trigger a degradation process (RNAi) that specifically silences the expression of a cognate mRNA. Our findings in this study showed that down regulation of CD40 gene expression in dendritic cells (DCs) by RNAi culminated to immune modulation. Effective delivery of siRNA into DCs would be a reasonable method for the blocking of CD40 gene expression at the cell surface without any effect on other genes and cell cytotoxicity. The effects of siRNA against CD40 mRNA on the function and phenotype of DCs were investigated. The DCs were separated from the mice spleen and then cultured in vitro. By the means of Lipofectamine2000, siRNA was delivered to the cells and the efficacy of transfection was estimated by flow cytometry. By Annexine V and Propidium Iodide staining, we could evaluate the transfected cells viability. Also, the mRNA expression and protein synthesis were assessed by real-time PCR and flow cytometry, respectively. Knocking down the CD40 gene in the DCs caused an increase in IL-4 production, decrease in IL-12 production and allostimulation activity. All together, these effects would stimulate Th2 cytokines production from allogenic T-cells in vitro.

Radar-to-Radar Interference Suppression for Distributed Radar Sensor Networks

Directory of Open Access Journals (Sweden)

Wen-Qin Wang

2014-01-01

Full Text Available Radar sensor networks, including bi- and multi-static radars, provide several operational advantages, like reduced vulnerability, good system flexibility and an increased radar cross-section. However, radar-to-radar interference suppression is a major problem in distributed radar sensor networks. In this paper, we present a cross-matched filtering-based radar-to-radar interference suppression algorithm. This algorithm first uses an iterative filtering algorithm to suppress the radar-to-radar interferences and, then, separately matched filtering for each radar. Besides the detailed algorithm derivation, extensive numerical simulation examples are performed with the down-chirp and up-chirp waveforms, partially overlapped or inverse chirp rate linearly frequency modulation (LFM waveforms and orthogonal frequency division multiplexing (ODFM chirp diverse waveforms. The effectiveness of the algorithm is verified by the simulation results.

Catastrophizing Interferes with Cognitive Modulation of Pain in Women with Fibromyalgia.

Science.gov (United States)

Ellingson, Laura D; Stegner, Aaron J; Schwabacher, Isaac J; Lindheimer, Jacob B; Cook, Dane B

2018-02-21

Pain modulation is a critical function of the nociceptive system that includes the ability to engage descending pain control systems to maintain a functional balance between facilitation and inhibition of incoming sensory stimuli. Dysfunctional pain modulation is associated with increased risk for chronic pain and is characteristic of fibromyalgia (FM). Catastrophizing is also common in FM. However, its influence on pain modulation is poorly understood. To determine the role of catastrophizing on central nervous system processing during pain modulation in FM via examining brain responses and pain sensitivity during an attention-distraction paradigm. Twenty FM patients and 18 healthy controls (CO) underwent functional magnetic resonance imaging while receiving pain stimuli, administered alone and during distracting cognitive tasks. Pain ratings were assessed after each stimulus. Catastrophizing was assessed with the Pain Catastrophizing Scale (PCS). The ability to modulate pain during distraction varied among FM patients and was associated with catastrophizing. This was demonstrated by significant positive relationships between PCS scores and pain ratings (P modulation did not differ between FM and CO (P > 0.05). FM patients with higher levels of catastrophizing were less able to distract themselves from pain, indicative of catastrophizing-related impairments in pain modulation. These results suggest that the tendency to catastrophize interacts with attention-resource allocation and may represent a mechanism of chronic pain exacerbation and/or maintenance. Reducing catastrophizing may improve FM symptoms via improving central nervous system regulation of pain.

Attention and memory protection: Interactions between retrospective attention cueing and interference.

Science.gov (United States)

Makovski, Tal; Pertzov, Yoni

2015-01-01

Visual working memory (VWM) and attention have a number of features in common, but despite extensive research it is still unclear how the two interact. Can focused attention improve VWM precision? Can it protect VWM from interference? Here we used a partial-report, continuous-response orientation memory task to examine how attention and interference affect different aspects of VWM and how they interact with one another. Both attention and interference were orthogonally manipulated during the retention interval. Attention was manipulated by presenting informative retro-cues, whereas interference was manipulated by introducing a secondary interfering task. Mixture-model analyses revealed that retro-cues, compared to uninformative cues, improved all aspects of performance: Attention increased recall precision and decreased guessing rate and swap-errors (reporting a wrong item in memory). Similarly, performing a secondary task impaired all aspects of the VWM task. In particular, an interaction between retro-cue and secondary task interference was found primarily for swap-errors. Together these results suggest that both the quantity and quality of VWM representations are sensitive to attention cueing and interference modulations, and they highlight the role of attention in protecting the feature-location associations needed to access the correct items in memory.

The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication.

Science.gov (United States)

Hill-Batorski, Lindsay; Halfmann, Peter; Neumann, Gabriele; Kawaoka, Yoshihiro

2013-12-01

Ebola virus (EBOV) is the causative agent of a severe hemorrhagic fever in humans with reported case fatality rates as high as 90%. There are currently no licensed vaccines or antiviral therapeutics to combat EBOV infections. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has antioxidative properties and protects cells from various stresses. Activated HO-1 was recently shown to have antiviral activity, potently inhibiting the replication of viruses such as hepatitis C virus and human immunodeficiency virus. However, the effect of HO-1 activation on EBOV replication remains unknown. To determine whether the upregulation of HO-1 attenuates EBOV replication, we treated cells with cobalt protoporphyrin (CoPP), a selective HO-1 inducer, and assessed its effects on EBOV replication. We found that CoPP treatment, pre- and postinfection, significantly suppressed EBOV replication in a manner dependent upon HO-1 upregulation and activity. In addition, stable overexpression of HO-1 significantly attenuated EBOV growth. Although the exact mechanism behind the antiviral properties of HO-1 remains to be elucidated, our data show that HO-1 upregulation does not attenuate EBOV entry or budding but specifically targets EBOV transcription/replication. Therefore, modulation of the cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV infection.

Selection Demands and Working Memory Mediate Interference during Naming

Directory of Open Access Journals (Sweden)

Julie W Hughes

2015-05-01

Analyzing RTs, we replicated previous SI effects in BCN in healthy subjects and patients (reported effects’ p’s < .05. Subjects responded more slowly to items in semantically related vs. unrelated groups, and this interference increased across cycles (evidence of increasing selection demands; Figures 1a/c. Indicative of WM, healthy subjects were faster to name items as the number of unrelated items to be named (i.e., remembered decreased. However, this was attenuated by selection demand, as there was no decrease in RTs across repeated related items (Figure 1b. Converging evidence from patients demonstrated more impaired selection capacity produced increasingly slower RTs across item positions within the related condition (high selection demand (Figure 1d. Larger WM capacity (rhyme probe but not category probe, p = .54 produced increasingly faster RTs across items positions in the unrelated condition (low selection demand (Figure 1e. Together, these findings suggest that both selection demand and phonological WM processes mediate interference during naming.

Synthetic peptide inhibitors of DNA replication in Staphylococcus aureus

DEFF Research Database (Denmark)

Løbner-Olesen, Anders; Kjelstrup, Susanne

F counterselection was developed to directly select for compounds able to disrupt selected interactions. We have subsequently constructed a cyclic peptide library for intracellular synthesis of cyclic peptides using known technology. Several cyclic peptides were able to interfere with oligomerization of Dna......N (), DnaB and DnaX (). Three peptides identified as inhibitors of DnaN have been purified. Two of these peptides inhibited growth as well as DNA replication in S. aureus. The minimal inhibitory concentration (MIC) of the peptides was approximately 50 g/ml. Overexpression of DnaN reduced the inhibitory...

Quasiparticle Interference on Cubic Perovskite Oxide Surfaces.

Science.gov (United States)

Okada, Yoshinori; Shiau, Shiue-Yuan; Chang, Tay-Rong; Chang, Guoqing; Kobayashi, Masaki; Shimizu, Ryota; Jeng, Horng-Tay; Shiraki, Susumu; Kumigashira, Hiroshi; Bansil, Arun; Lin, Hsin; Hitosugi, Taro

2017-08-25

We report the observation of coherent surface states on cubic perovskite oxide SrVO_{3}(001) thin films through spectroscopic-imaging scanning tunneling microscopy. A direct link between the observed quasiparticle interference patterns and the formation of a d_{xy}-derived surface state is supported by first-principles calculations. We show that the apical oxygens on the topmost VO_{2} plane play a critical role in controlling the coherent surface state via modulating orbital state.

Analysis of Intercarrier Interference Cancellation Scheme in OFDM Systems

Directory of Open Access Journals (Sweden)

Nasir Salh Almisbah

2012-06-01

Full Text Available Abstract: Orthogonal Frequency Division Multiplexing (OFDM is an emerging multi-carrier modulation scheme, which has been adopted for several wireless standards such as IEEE 802.11a and HiperLAN2. In OFDM systems, the performance is very sensitive to subcarrier frequency errors (offset. This paper shows the analysis and derivations of intercarrier interference (ICI complex gain that used in self-cancellation scheme and its dependence on subcarrier frequency offset. Simulation shows that better improvement in performance is achieved for systems that use this cancellation scheme. Moreover, analysis and simulation show that theoretical carrier-to-interference ratio (CIR for OFDM with cancellation scheme is greater than conventional one by more than 14dB.

Optimization of Modulation Waveforms for Improved EMI Attenuation in Switching Frequency Modulated Power Converters

Directory of Open Access Journals (Sweden)

Deniss Stepins

2015-01-01

Full Text Available Electromagnetic interference (EMI is one of the major problems of switching power converters. This paper is devoted to switching frequency modulation used for conducted EMI suppression in switching power converters. Comprehensive theoretical analysis of switching power converter conducted EMI spectrum and EMI attenuation due the use of traditional ramp and multislope ramp modulation waveforms is presented. Expressions to calculate EMI spectrum and attenuation are derived. Optimization procedure of the multislope ramp modulation waveform is proposed to get maximum benefits from switching frequency modulation for EMI reduction. Experimental verification is also performed to prove that the optimized multislope ramp modulation waveform is very useful solution for effective EMI reduction in switching power converters.

Distributional Replication

OpenAIRE

Beare, Brendan K.

2009-01-01

Suppose that X and Y are random variables. We define a replicating function to be a function f such that f(X) and Y have the same distribution. In general, the set of replicating functions for a given pair of random variables may be infinite. Suppose we have some objective function, or cost function, defined over the set of replicating functions, and we seek to estimate the replicating function with the lowest cost. We develop an approach to estimating the cheapest replicating function that i...

Electromagnetically induced interference in a superconducting flux qubit

International Nuclear Information System (INIS)

Du lingjie; Yu Yang; Lan Dong

2013-01-01

Interaction between quantum two-level systems (qubits) and electromagnetic fields can provide additional coupling channels to qubit states. In particular, the interwell relaxation or Rabi oscillations, resulting, respectively, from the multi- or single-mode interaction, can produce effective crossovers, leading to electromagnetically induced interference in microwave driven qubits. The environment is modeled by a multimode thermal bath, generating the interwell relaxation. Relaxation induced interference, independent of the tunnel coupling, provides deeper understanding to the interaction between the qubits and their environment. It also supplies a useful tool to characterize the relaxation strength as well as the characteristic frequency of the bath. In addition, we demonstrate the relaxation can generate population inversion in a strongly driving two-level system. On the other hand, different from Rabi oscillations, Rabi-oscillation-induced interference involves more complicated and modulated photon exchange thus offers an alternative means to manipulate the qubit, with more controllable parameters including the strength and position of the tunnel coupling. It also provides a testing ground for exploring nonlinear quantum phenomena and quantum state manipulation in qubits either with or without crossover structure.

Chromatin Immunoprecipitation of Replication Factors Moving with the Replication Fork

OpenAIRE

Rapp, Jordan B.; Ansbach, Alison B.; Noguchi, Chiaki; Noguchi, Eishi

2009-01-01

Replication of chromosomes involves a variety of replication proteins including DNA polymerases, DNA helicases, and other accessory factors. Many of these proteins are known to localize at replication forks and travel with them as components of the replisome complex. Other proteins do not move with replication forks but still play an essential role in DNA replication. Therefore, in order to understand the mechanisms of DNA replication and its controls, it is important to examine localization ...

Ancient mtDNA genetic variants modulate mtDNA transcription and replication.

Directory of Open Access Journals (Sweden)

Sarit Suissa

2009-05-01

Full Text Available Although the functional consequences of mitochondrial DNA (mtDNA genetic backgrounds (haplotypes, haplogroups have been demonstrated by both disease association studies and cell culture experiments, it is not clear which of the mutations within the haplogroup carry functional implications and which are "evolutionary silent hitchhikers". We set forth to study the functionality of haplogroup-defining mutations within the mtDNA transcription/replication regulatory region by in vitro transcription, hypothesizing that haplogroup-defining mutations occurring within regulatory motifs of mtDNA could affect these processes. We thus screened >2500 complete human mtDNAs representing all major populations worldwide for natural variation in experimentally established protein binding sites and regulatory regions comprising a total of 241 bp in each mtDNA. Our screen revealed 77/241 sites showing point mutations that could be divided into non-fixed (57/77, 74% and haplogroup/sub-haplogroup-defining changes (i.e., population fixed changes, 20/77, 26%. The variant defining Caucasian haplogroup J (C295T increased the binding of TFAM (Electro Mobility Shift Assay and the capacity of in vitro L-strand transcription, especially of a shorter transcript that maps immediately upstream of conserved sequence block 1 (CSB1, a region associated with RNA priming of mtDNA replication. Consistent with this finding, cybrids (i.e., cells sharing the same nuclear genetic background but differing in their mtDNA backgrounds harboring haplogroup J mtDNA had a >2 fold increase in mtDNA copy number, as compared to cybrids containing haplogroup H, with no apparent differences in steady state levels of mtDNA-encoded transcripts. Hence, a haplogroup J regulatory region mutation affects mtDNA replication or stability, which may partially account for the phenotypic impact of this haplogroup. Our analysis thus demonstrates, for the first time, the functional impact of particular mt

Multifaceted regulation of translational readthrough by RNA replication elements in a tombusvirus.

Directory of Open Access Journals (Sweden)

Peter A Cimino

2011-12-01

Full Text Available Translational readthrough of stop codons by ribosomes is a recoding event used by a variety of viruses, including plus-strand RNA tombusviruses. Translation of the viral RNA-dependent RNA polymerase (RdRp in tombusviruses is mediated using this strategy and we have investigated this process using a variety of in vitro and in vivo approaches. Our results indicate that readthrough generating the RdRp requires a novel long-range RNA-RNA interaction, spanning a distance of ∼3.5 kb, which occurs between a large RNA stem-loop located 3'-proximal to the stop codon and an RNA replication structure termed RIV at the 3'-end of the viral genome. Interestingly, this long-distance RNA-RNA interaction is modulated by mutually-exclusive RNA structures in RIV that represent a type of RNA switch. Moreover, a different long-range RNA-RNA interaction that was previously shown to be necessary for viral RNA replicase assembly was also required for efficient readthrough production of the RdRp. Accordingly, multiple replication-associated RNA elements are involved in modulating the readthrough event in tombusviruses and we propose an integrated mechanistic model to describe how this regulatory network could be advantageous by (i providing a quality control system for culling truncated viral genomes at an early stage in the replication process, (ii mediating cis-preferential replication of viral genomes, and (iii coordinating translational readthrough of the RdRp with viral genome replication. Based on comparative sequence analysis and experimental data, basic elements of this regulatory model extend to other members of Tombusviridae, as well as to viruses outside of this family.

Replication Catastrophe

DEFF Research Database (Denmark)

Toledo, Luis; Neelsen, Kai John; Lukas, Jiri

2017-01-01

Proliferating cells rely on the so-called DNA replication checkpoint to ensure orderly completion of genome duplication, and its malfunction may lead to catastrophic genome disruption, including unscheduled firing of replication origins, stalling and collapse of replication forks, massive DNA...... breakage, and, ultimately, cell death. Despite many years of intensive research into the molecular underpinnings of the eukaryotic replication checkpoint, the mechanisms underlying the dismal consequences of its failure remain enigmatic. A recent development offers a unifying model in which the replication...... checkpoint guards against global exhaustion of rate-limiting replication regulators. Here we discuss how such a mechanism can prevent catastrophic genome disruption and suggest how to harness this knowledge to advance therapeutic strategies to eliminate cancer cells that inherently proliferate under...

Impact of ageing on problem size and proactive interference in arithmetic facts solving.

Science.gov (United States)

Archambeau, Kim; De Visscher, Alice; Noël, Marie-Pascale; Gevers, Wim

2018-02-01

Arithmetic facts (AFs) are required when solving problems such as "3 × 4" and refer to calculations for which the correct answer is retrieved from memory. Currently, two important effects that modulate the performance in AFs have been highlighted: the problem size effect and the proactive interference effect. The aim of this study is to investigate possible age-related changes of the problem size effect and the proactive interference effect in AF solving. To this end, the performance of young and older adults was compared in a multiplication production task. Furthermore, an independent measure of proactive interference was assessed to further define the architecture underlying this effect in multiplication solving. The results indicate that both young and older adults were sensitive to the effects of interference and of the problem size. That is, both interference and problem size affected performance negatively: the time needed to solve a multiplication problem increases as the level of interference and the size of the problem increase. Regarding the effect of ageing, the problem size effect remains constant with age, indicating a preserved AF network in older adults. Interestingly, sensitivity to proactive interference in multiplication solving was less pronounced in older than in younger adults suggesting that part of the proactive interference has been overcome with age.

Geometric-Phase Interference in a Mn12 Single-Molecule Magnet with Truly Fourfold Symmetry

Science.gov (United States)

Friedman, Jonathan

2014-03-01

A single-molecule magnet (SMM) is a large-spin system with an anisotropy barrier separating preferred ``up'' and ``down'' orientations. The spin can tunnel between these directions when an external longitudinal magnetic field brings levels in opposite wells into resonance. When there exist more than one energetically equivalent paths for tunneling, those paths can interfere, a geometric-phase effect that modulates the rate at which spins flip direction. The interference can be controlled by a magnetic field applied perpendicular to the spin's easy magnetization axis. In a ground-breaking experiment, Wernsdorfer and Sessoli found oscillations in the probability of spin tunneling as a function of the field applied along the hard axis of the Fe8 SMM. This observation confirmed a theoretical prediction by Garg. Similar geometric-phase interference has been observed in other SMMs that have effective two-fold symmetry, where tunneling involves the interference between two equal-amplitude paths. Such interference effects have not previously been seen in systems with four-fold rotational symmetry. In recent work, my group has seen evidence of the observation of a geometric-phase interference effect in the Mn12-tBuAc SMM, a variant of the bellwether Mn12-Ac SMM that has true four-fold rotational symmetry (being free of the solvent disorder that breaks the four-fold symmetry in the latter). The spin relaxation rate as a function of the applied transverse magnetic field shows a modulated behavior, with retarded relaxation near where one expects destructive interference between tunneling paths associated with excited states. Tuning the direction of the transverse field away from the hard axis washes out the observed interference effect by favoring one tunneling path over others. Detailed master-equation calculations are used to fit the observed behavior and yield anisotropy parameters consistent with values determined by other groups. Unlike previous observations of geometric

Performance Evaluation of Cognitive Interference Channels Using a Spectrum Overlay Strategy

Science.gov (United States)

Knoblock, Eric J.

2018-01-01

The use of cognitive radios (CR) and cooperative communications techniques may assist in interference mitigation via sensing of the environment and dynamically altering communications parameters through the use of various mechanisms - one of which is the overlay technique. This report provides a performance analysis of an interference channel with a cognitive transceiver operating in an overlay configuration to evaluate the gains from using cognition. As shown in this report, a cognitive transceiver can simultaneously share spectrum while enhancing performance of non-cognitive nodes via knowledge of the communications channel as well as knowledge of neighboring users' modulation and coding schemes.

Cost-effective, compact and high-speed integrable multi-mode interference modulator

NARCIS (Netherlands)

Lenstra, Daan; Yao, Weiming; Cardarelli, Simone; Mink, Jan

2017-01-01

Theoretical analysis of the modulation performance of this wave-guide device shows great potential when combined with a single-mode laser on a monolithic optical chip. On the basis of the reversed-bias electro-optic effect, modulation speeds surmounting 25 Gbit/s with 10 dB extinction ratio are

Database Replication Prototype

OpenAIRE

Vandewall, R.

2000-01-01

This report describes the design of a Replication Framework that facilitates the implementation and com-parison of database replication techniques. Furthermore, it discusses the implementation of a Database Replication Prototype and compares the performance measurements of two replication techniques based on the Atomic Broadcast communication primitive: pessimistic active replication and optimistic active replication. The main contributions of this report can be split into four parts....

Investigation of focusing and correcting aberrations with binary amplitude and polarization modulation.

Science.gov (United States)

Fiala, Peter; Li, Yunqi; Dorrer, Christophe

2018-02-01

We investigate the focusing and correcting wavefront aberration of an optical wave using binary amplitude and polarization modulation. Focusing is performed by selectively modulating the field in different zones of the pupil to obtain on-axis constructive interference at a given distance. The conventional Soret zone plate (binary amplitude profile) is expanded to a polarization Soret zone plate with twice the focusing efficiency. Binary pixelated devices that approximate the sinusoidal transmission profile of a Gabor zone plate by spatial dithering are also investigated with amplitude and polarization modulation. Wavefront aberrations are corrected by modulation of the field in the pupil plane to prevent destructive interference in the focal plane of an ideal focusing element. Polarization modulation improves the efficiency obtained by amplitude-only modulation, with a gain that depends on the aberration. Experimental results obtained with Cr-on-glass devices for amplitude modulation and liquid crystal devices operating in the Mauguin condition for polarization modulation are in very good agreement with simulations.

Structural diversity and dynamics of genomic replication origins in Schizosaccharomyces pombe

Science.gov (United States)

Cotobal, Cristina; Segurado, Mónica; Antequera, Francisco

2010-01-01

DNA replication origins (ORI) in Schizosaccharomyces pombe colocalize with adenine and thymine (A+T)-rich regions, and earlier analyses have established a size from 0.5 to over 3 kb for a DNA fragment to drive replication in plasmid assays. We have asked what are the requirements for ORI function in the chromosomal context. By designing artificial ORIs, we have found that A+T-rich fragments as short as 100 bp without homology to S. pombe DNA are able to initiate replication in the genome. On the other hand, functional dissection of endogenous ORIs has revealed that some of them span a few kilobases and include several modules that may be as short as 25–30 contiguous A+Ts capable of initiating replication from ectopic chromosome positions. The search for elements with these characteristics across the genome has uncovered an earlier unnoticed class of low-efficiency ORIs that fire late during S phase. These results indicate that ORI specification and dynamics varies widely in S. pombe, ranging from very short elements to large regions reminiscent of replication initiation zones in mammals. PMID:20094030

μ-opioid modulation of HIV-1 coreceptor expressionand HIV-1 replication

International Nuclear Information System (INIS)

Steele, Amber D.; Henderson, Earl E.; Rogers, Thomas J.

2003-01-01

A substantial proportion of HIV-1-infected individuals are intravenous drug users (IVDUs) who abuse opiates. Opioids induce a number of immunomodulatory effects that may directly influence HIV-1 disease progression. In the present report, we have investigated the effect of opioids on the expression of the major HIV-1 coreceptors CXCR4 and CCR5. For these studies we have focused on opiates which are ligands for the μ-opioid receptor. Our results show that DAMGO, a selective μ-opioid agonist, increases CXCR4 and CCR5 expression in both CD3 + lymphoblasts and CD14 + monocytes three- to fivefold. Furthermore, DAMGO-induced elevation of HIV-1 coreceptor expression translates into enhanced replication of both X4 and R5 viral strains of HIV-1. We have confirmed the role of the μ-opioid receptor based on the ability of a μ-opioid receptor-selective antagonist to block the effects of DAMGO. We have also found that morphine enhances CXCR4 and CCR5 expression and subsequently increases both X4 and R5 HIV-1 infection. We suggest that the capacity of μ-opioids to increase HIV-1 coreceptor expression and replication may promote viral binding, trafficking of HIV-1-infected cells, and enhanced disease progression

Mutant p53 perturbs DNA replication checkpoint control through TopBP1 and Treslin.

Science.gov (United States)

Liu, Kang; Lin, Fang-Tsyr; Graves, Joshua D; Lee, Yu-Ju; Lin, Weei-Chin

2017-05-09

Accumulating evidence supports the gain-of-function of mutant forms of p53 (mutp53s). However, whether mutp53 directly perturbs the DNA replication checkpoint remains unclear. Previously, we have demonstrated that TopBP1 forms a complex with mutp53s and mediates their gain-of-function through NF-Y and p63/p73. Akt phosphorylates TopBP1 and induces its oligomerization, which inhibits its ATR-activating function. Here we show that various contact and conformational mutp53s bypass Akt to induce TopBP1 oligomerization and attenuate ATR checkpoint response during replication stress. The effect on ATR response caused by mutp53 can be exploited in a synthetic lethality strategy, as depletion of another ATR activator, DNA2, in mutp53-R273H-expressing cancer cells renders cells hypersensitive to cisplatin. Expression of mutp53-R273H also makes cancer cells more sensitive to DNA2 depletion or DNA2 inhibitors. In addition to ATR-activating function during replication stress, TopBP1 interacts with Treslin in a Cdk-dependent manner to initiate DNA replication during normal growth. We find that mutp53 also interferes with TopBP1 replication function. Several contact, but not conformational, mutp53s enhance the interaction between TopBP1 and Treslin and promote DNA replication despite the presence of a Cdk2 inhibitor. Together, these data uncover two distinct mechanisms by which mutp53 enhances DNA replication: ( i ) Both contact and conformational mutp53s can bind TopBP1 and attenuate the checkpoint response to replication stress, and ( ii ) during normal growth, contact (but not conformational) mutp53s can override the Cdk2 requirement to promote replication by facilitating the TopBP1/Treslin interaction.

The Replication Recipe: What makes for a convincing replication?

NARCIS (Netherlands)

Brandt, M.J.; IJzerman, H.; Dijksterhuis, A.J.; Farach, F.J.; Geller, J.; Giner-Sorolla, R.; Grange, J.A.; Perugini, M.; Spies, J.R.; Veer, A. van 't

2014-01-01

Psychological scientists have recently started to reconsider the importance of close replications in building a cumulative knowledge base; however, there is no consensus about what constitutes a convincing close replication study. To facilitate convincing close replication attempts we have developed

The replication recipe : What makes for a convincing replication?

NARCIS (Netherlands)

Brandt, M.J.; IJzerman, H.; Dijksterhuis, Ap; Farach, Frank J.; Geller, Jason; Giner-Sorolla, Roger; Grange, James A.; Perugini, Marco; Spies, Jeffrey R.; van 't Veer, Anna

Psychological scientists have recently started to reconsider the importance of close replications in building a cumulative knowledge base; however, there is no consensus about what constitutes a convincing close replication study. To facilitate convincing close replication attempts we have developed

Control and near-field detection of surface plasmon interference patterns.

Science.gov (United States)

Dvořák, Petr; Neuman, Tomáš; Břínek, Lukáš; Šamořil, Tomáš; Kalousek, Radek; Dub, Petr; Varga, Peter; Šikola, Tomáš

2013-06-12

The tailoring of electromagnetic near-field properties is the central task in the field of nanophotonics. In addition to 2D optics for optical nanocircuits, confined and enhanced electric fields are utilized in detection and sensing, photovoltaics, spatially localized spectroscopy (nanoimaging), as well as in nanolithography and nanomanipulation. For practical purposes, it is necessary to develop easy-to-use methods for controlling the electromagnetic near-field distribution. By imaging optical near-fields using a scanning near-field optical microscope, we demonstrate that surface plasmon polaritons propagating from slits along the metal-dielectric interface form tunable interference patterns. We present a simple way how to control the resulting interference patterns both by variation of the angle between two slits and, for a fixed slit geometry, by a proper combination of laser beam polarization and inhomogeneous far-field illumination of the structure. Thus the modulation period of interference patterns has become adjustable and new variable patterns consisting of stripelike and dotlike motifs have been achieved, respectively.

The Tocotrienol-Rich Fraction Is Superior to Tocopherol in Promoting Myogenic Differentiation in the Prevention of Replicative Senescence of Myoblasts.

Directory of Open Access Journals (Sweden)

Shy Cian Khor

Full Text Available Aging results in a loss of muscle mass and strength. Myoblasts play an important role in maintaining muscle mass through regenerative processes, which are impaired during aging. Vitamin E potentially ameliorates age-related phenotypes. Hence, this study aimed to determine the effects of the tocotrienol-rich fraction (TRF and α-tocopherol (ATF in protecting myoblasts from replicative senescence and promoting myogenic differentiation. Primary human myoblasts were cultured into young and senescent stages and were then treated with TRF or ATF for 24 h, followed by an analysis of cell proliferation, senescence biomarkers, cellular morphology and differentiation. Our data showed that replicative senescence impaired the normal regenerative processes of myoblasts, resulting in changes in cellular morphology, cell proliferation, senescence-associated β-galactosidase (SA-β-gal expression, myogenic differentiation and myogenic regulatory factors (MRFs expression. Treatment with both TRF and ATF was beneficial to senescent myoblasts in reclaiming the morphology of young cells, improved cell viability and decreased SA-β-gal expression. However, only TRF treatment increased BrdU incorporation in senescent myoblasts, as well as promoted myogenic differentiation through the modulation of MRFs at the mRNA and protein levels. MYOD1 and MYOG gene expression and myogenin protein expression were modulated in the early phases of myogenic differentiation. In conclusion, the tocotrienol-rich fraction is superior to α-tocopherol in ameliorating replicative senescence-related aberration and promoting differentiation via modulation of MRFs expression, indicating vitamin E potential in modulating replicative senescence of myoblasts.

Interference Control In Elderly Bilinguals: Appearances Can Be Misleading.

Science.gov (United States)

Ansaldo, Ana Inés; Ghazi-Saidi, Ladan; Adrover-Roig, Daniel

2015-01-01

Bilingualism has been associated with successful aging. In particular, research on the cognitive advantages of bilingualism suggests that it can enhance control over interference and help delay the onset of dementia signs. However, the evidence on the so-called cognitive advantage is not unanimous; furthermore, little is known about the neural basis of this supposed cognitive advantage in bilingual as opposed to monolingual elderly populations. In this study, elderly bilingual and monolingual participants performed a visuospatial interference control task during functional magnetic resonance imaging (fMRI) scanning. Response times and accuracy rates were calculated for congruent and incongruent conditions of the Simon task, and the neurofunctional correlates of performance on the Simon task were examined. The results showed equivalent performance on the Simon task across groups but different underlying neural substrates in the two groups. With incongruent trials, monolinguals activated the right middle frontal gyrus, whereas bilinguals relied upon the left inferior parietal lobule. These results show that elderly bilinguals and monolinguals have equivalent interference control abilities, but relay on different neural substrates. Thus, while monolinguals show a classical PASA (posterior-anterior shift in aging) effect, recruiting frontal areas, bilinguals activate visuospatial processing alone and thus do not show this posterior-anterior shift. Moreover, a modulation of frontal activity with task-dynamic control of interference, observed in the elderly bilingual group alone, suggests that elderly bilinguals deal with interference control without recruiting a circuit that is particularly vulnerable to aging.

[Efficacy of siRNA on feline leukemia virus replication in vitro].

Science.gov (United States)

Lehmann, Melanie; Weber, Karin; Rauch, Gisep; Hofmann-Lehmann, Regina; Hosie, Margaret J; Meli, Marina L; Hartmann, Katrin

2015-01-01

Feline leukemia virus (FeLV) can lead to severe clinical signs in cats. Until now, there is no effective therapy for FeLV-infected cats. RNA interference-based antiviral therapy is a new concept. Specific small interfering RNA (siRNA) are designed complementary to the mRNA of a target region, and thus inhibit replication. Several studies have proven efficacy of siRNAs in inhibiting virus replication. The aim of this study was to evaluate the inhibitory potential of siRNAs against FeLV replication in vitro. siRNAs against the FeLV env gene and the host cell surface receptor (feTHTR1) which is used by FeLV-A for entry as well as siRNA that were not complementary to the FeLV or cat genome, were tested. Crandell feline kidney cells (CrFK cells) were transfected with FeLV-A/Glasgow-1. On day 13, infected cells were transfected with siRNAs. As control, cells were mock-transfected or treated with azidothymidine (AZT) (5 μg/ml). Culture supernatants were analyzed for FeLV RNA using quantitative real-time RT-PCR and for FeLV p27 by ELISA every 24 hours for five days. All siRNAs significantly reduced viral RNA and p27 production, starting after 48 hours. The fact that non-complementary siRNAs also inhibited virus replication may lead to the conclusion that unspecific mechanisms rather than specific binding lead to inhibition.

Multiscale analysis of replication technique efficiency for 3D roughness characterization of manufactured surfaces

Science.gov (United States)

Jolivet, S.; Mezghani, S.; El Mansori, M.

2016-09-01

The replication of topography has been generally restricted to optimizing material processing technologies in terms of statistical and single-scale features such as roughness. By contrast, manufactured surface topography is highly complex, irregular, and multiscale. In this work, we have demonstrated the use of multiscale analysis on replicates of surface finish to assess the precise control of the finished replica. Five commercial resins used for surface replication were compared. The topography of five standard surfaces representative of common finishing processes were acquired both directly and by a replication technique. Then, they were characterized using the ISO 25178 standard and multiscale decomposition based on a continuous wavelet transform, to compare the roughness transfer quality at different scales. Additionally, atomic force microscope force modulation mode was used in order to compare the resins’ stiffness properties. The results showed that less stiff resins are able to replicate the surface finish along a larger wavelength band. The method was then tested for non-destructive quality control of automotive gear tooth surfaces.

Steps in Modular Specifications for Concurrent Modules

DEFF Research Database (Denmark)

Da Rocha Pinto, Pedro; Dinsdale-Young, Thomas; Gardner, Philippa

2015-01-01

The specification of a concurrent program module is a difficult problem. The specifications must be strong enough to enable reasoning about the intended clients without reference to the underlying module implementation. We survey a range of verification techniques for specifying concurrent module......, in particular highlighting four key concepts: auxiliary state, interference abstraction, resource ownership and atomicity. We show how these concepts combine to provide powerful approaches to specifying concurrent modules.......The specification of a concurrent program module is a difficult problem. The specifications must be strong enough to enable reasoning about the intended clients without reference to the underlying module implementation. We survey a range of verification techniques for specifying concurrent modules...

Quantum interference effects at room temperature in OPV-based single-molecule junctions

DEFF Research Database (Denmark)

Arroyo, Carlos R.; Frisenda, Riccardo; Moth-Poulsen, Kasper

2013-01-01

Interference effects on charge transport through an individual molecule can lead to a notable modulation and suppression on its conductance. In this letter, we report the observation of quantum interference effects occurring at room temperature in single-molecule junctions based on oligo(3......)-phenylenevinylene (OPV3) derivatives, in which the central benzene ring is coupled to either para- or meta-positions. Using the break-junction technique, we find that the conductance for a single meta-OPV3 molecule wired between gold electrodes is one order of magnitude smaller than that of a para-OPV3 molecule...

Interference Effects in the Optical Second Harmonic Generation from Ultrathin Alkali Films

DEFF Research Database (Denmark)

Balzer, F.; Rubahn, Horst-Günter

2000-01-01

Interference effects are shown to strongly modulate the transmission second harmonic signal (fundamental wavelength 1067 nm) from rough alkali island films grown on insulating substrates if one varies the angle of incidence. Depending on growth conditions and substrate thickness, the measured...... second harmonic dependencies can be interpreted in terms of interference between frontside and rearside adsorbed islands or by taking into account the morphology of the adsorbed alkali islands. By the use of different polarization combinations of both pump and reflected second harmonic wave we obtain...... accurate values of the ratios of the relevant nonlinear optical coefficients....

Nanoscale surface characterization using laser interference microscopy

Science.gov (United States)

Ignatyev, Pavel S.; Skrynnik, Andrey A.; Melnik, Yury A.

2018-03-01

Nanoscale surface characterization is one of the most significant parts of modern materials development and application. The modern microscopes are expensive and complicated tools, and its use for industrial tasks is limited due to laborious sample preparation, measurement procedures, and low operation speed. The laser modulation interference microscopy method (MIM) for real-time quantitative and qualitative analysis of glass, metals, ceramics, and various coatings has a spatial resolution of 0.1 nm for vertical and up to 100 nm for lateral. It is proposed as an alternative to traditional scanning electron microscopy (SEM) and atomic force microscopy (AFM) methods. It is demonstrated that in the cases of roughness metrology for super smooth (Ra >1 nm) surfaces the application of a laser interference microscopy techniques is more optimal than conventional SEM and AFM. The comparison of semiconductor test structure for lateral dimensions measurements obtained with SEM and AFM and white light interferometer also demonstrates the advantages of MIM technique.

2',3'-cyclic nucleotide 3'-phosphodiesterases inhibit hepatitis B virus replication.

Directory of Open Access Journals (Sweden)

Hui Ma

Full Text Available 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP is a member of the interferon-stimulated genes, which includes isoforms CNP1 and CNP2. CNP1 is locally expressed in the myelin sheath but CNP2 is additionally expressed at low levels outside the nervous system. CNPs regulate multiple cellular functions and suppress protein production by association with polyadenylation of mRNA. Polyadenylation of Hepatitis B virus (HBV RNAs is crucial for HBV replication. Whether CNPs interact with polyadenylation signal of HBV RNAs and interfere HBV replication is unknown. In this study, we evaluated expressions of CNP isoforms in hepatoma cell lines and their effects on HBV replication. We found that CNP2 is moderately expressed and gently responded to interferon treatment in HepG2, but not in Huh7 cells. The CNP1 and CNP2 potently inhibited HBV production by blocking viral proteins synthesis and reducing viral RNAs, respectively. In chronic hepatitis B patients, CNP was expressed in most of HBV-infected hepatocytes of liver specimens. Knockdown of CNP expression moderately improved viral production in the HepG2.2.15 cells treated with IFN-α. In conclusion, CNP might be a mediator of interferon-induced response against HBV.

Beamforming design with proactive interference cancelation in MISO interference channels

Science.gov (United States)

Li, Yang; Tian, Yafei; Yang, Chenyang

2015-12-01

In this paper, we design coordinated beamforming at base stations (BSs) to facilitate interference cancelation at users in interference networks, where each BS is equipped with multiple antennas and each user is with a single antenna. By assuming that each user can select the best decoding strategy to mitigate the interference, either canceling the interference after decoding when it is strong or treating it as noise when it is weak, we optimize the beamforming vectors that maximize the sum rate for the networks under different interference scenarios and find the solutions of beamforming with closed-form expressions. The inherent design principles are then analyzed, and the performance gain over passive interference cancelation is demonstrated through simulations in heterogeneous cellular networks.

Role of the recoil effect in two-center interference in X-ray photoionization

International Nuclear Information System (INIS)

Ueda, K.; Liu, X.-J.; Pruemper, G.; Lischke, T.; Tanaka, T.; Hoshino, M.; Tanaka, H.; Minkov, I.; Kimberg, V.; Gel'mukhanov, F.

2006-01-01

X-ray photoelectron spectra of the N 2 molecule are studied both experimentally and theoretically in the extended energy region up to 1 keV. The ratio of the photoionization cross sections for the gerade and ungerade core levels displays a modulation in the high energy region caused by the two-center interference, as predicted by Cohen and Fano (CF) in 1966. The physical background of this CF effect is the same as in Young's double-slit experiment. We have found that the interference pattern deviates significantly from the CF prediction. The origin of such a breakdown of the CF formula is the scattering of the photoelectron inside the molecule and the momentum transfer from the emitted fast photoelectron to the nuclei. Usually the recoil effect is small. We show that the electron recoil strongly affects the two-center interference pattern. Both stationary and dynamical aspects of the recoil effect shed light on the role of the momentum exchange in the two-center interference

Methamphetamine inhibits HIV-1 replication in CD4+ T cells by modulating anti-HIV-1 miRNA expression.

Science.gov (United States)

Mantri, Chinmay K; Mantri, Jyoti V; Pandhare, Jui; Dash, Chandravanu

2014-01-01

Methamphetamine is the second most frequently used illicit drug in the United States. Methamphetamine abuse is associated with increased risk of HIV-1 acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. Although a direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be established in patients, methamphetamine has been shown to increase HIV-1 replication in macrophages, dendritic cells, and cells of HIV transgenic mice. Intriguingly, the effects of methamphetamine on HIV-1 replication in human CD4(+) T cells that serve as the primary targets of infection in vivo are not clearly understood. Therefore, we examined HIV-1 replication in primary CD4(+) T cells in the presence of methamphetamine in a dose-dependent manner. Our results demonstrate that methamphetamine had a minimal effect on HIV-1 replication at concentrations of 1 to 50 μmol/L. However, at concentrations >100 μmol/L, it inhibited HIV-1 replication in a dose-dependent manner. We also discovered that methamphetamine up-regulated the cellular anti-HIV-1 microRNAs (miR-125b, miR-150, and miR-28-5p) in CD4(+) T cells. Knockdown experiments illustrated that up-regulation of the anti-HIV miRNAs inhibited HIV-1 replication. These results are contrary to the paradigm that methamphetamine accentuates HIV-1 pathogenesis by increasing HIV-1 replication. Therefore, our findings underline the complex interaction between drug use and HIV-1 and necessitate comprehensive understanding of the effects of methamphetamine on HIV-1 pathogenesis. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Measurement of replication structures at the nanometer scale using super-resolution light microscopy.

Science.gov (United States)

Baddeley, D; Chagin, V O; Schermelleh, L; Martin, S; Pombo, A; Carlton, P M; Gahl, A; Domaing, P; Birk, U; Leonhardt, H; Cremer, C; Cardoso, M C

2010-01-01

DNA replication, similar to other cellular processes, occurs within dynamic macromolecular structures. Any comprehensive understanding ultimately requires quantitative data to establish and test models of genome duplication. We used two different super-resolution light microscopy techniques to directly measure and compare the size and numbers of replication foci in mammalian cells. This analysis showed that replication foci vary in size from 210 nm down to 40 nm. Remarkably, spatially modulated illumination (SMI) and 3D-structured illumination microscopy (3D-SIM) both showed an average size of 125 nm that was conserved throughout S-phase and independent of the labeling method, suggesting a basic unit of genome duplication. Interestingly, the improved optical 3D resolution identified 3- to 5-fold more distinct replication foci than previously reported. These results show that optical nanoscopy techniques enable accurate measurements of cellular structures at a level previously achieved only by electron microscopy and highlight the possibility of high-throughput, multispectral 3D analyses.

Characteristics of temporal modulation in nonlinear propagation of broad-band lasers stacked by chirped pulses

International Nuclear Information System (INIS)

Wang Youwen; Chen Liezun; Zhang Lifu; Deng Jianqin; Zhang Jin; Wen Shuangchun; Fu Xiquan; Fan Dianyuan

2010-01-01

Characteristics of the temporal modulation riding on broad-band lasers stacked by chirped pulses are numerically investigated in nonlinear propagation. For the case of normal dispersion, the temporal modulations induced by interference among pulses and added artificially to simulate the noise weaken gradually with the increase of the propagation distance. For the case of anomalous dispersion, the temporal modulations induced by interference among pulses grow slowly at first, and start to grow rapidly after a long propagation distance; in contrast, the temporal modulations added artificially grow rapidly from the begin, indicating that the temporal peak of damage risk to the optics can be formed easily. (authors)

Effect of deoxyribonucleic acid replication inhibitors on bacterial recombination

International Nuclear Information System (INIS)

Canosi, U.; Siccardi, A.G.; Falaschi, A.; Mazza, G.

1976-01-01

Two inhibitors of replicative deoxyribonucleic acid (DNA) synthesis, nalidixic acid (NAL) and 6-(p-hydroxyphenylazo)-uracil (HPUra), showed different effects on genetic recombination and DNA repair in Bacillus subtilis. Previous work (Pedrini et al., 1972) showed that NAL does not interfere with the transformation process of B. subtilis. The results reported in this work demonstrated that the drug was also without effect on the transfection SPP1 or SPO-1 phage DNA (a process that requires a recombination event). The drug was also ineffective on the host cell reactivation of ultraviolet-irradiated SPP1 phage, as well as on transfection with ultraviolet-irradiated DNA of the same phage. HPUra instead markedly reduced the transformation process, as well as transfection, by SPO-1 DNA, but it did not affect the host cell reactivation of SPO-1 phage. In conclusion, whereas the NAL target seems to be specific for replicative DNA synthesis, the HPUra target (i.e., the DNA polymerase III of B. subtilis) seems to be involved also in recombination, but not in the excision repair process. The mutations conferring NAL and HPUra resistance used in this work were mapped by PBS-1 transduction

Electro-optic polymeric reflection modulator based on plasmonic metamaterial

Science.gov (United States)

Abbas, A.; Swillam, M.

2018-02-01

A novel low power design for polymeric Electro-Optic reflection modulator is proposed based on the Extraordinary Reflection of light from multilayer structure consisting of a plasmonic metasurface with a periodic structure of sub wavelength circular apertures in a gold film above a thin layer of EO polymer and above another thin gold layer. The interference of the different reflected beams from different layer construct the modulated beam, The applied input driving voltage change the polymer refractive index which in turn determine whether the interference is constructive or destructive, so both phase and intensity modulation could be achieved. The resonant wavelength is tuned to the standard telecommunication wavelength 1.55μm, at this wavelength the reflection is minimum, while the absorption is maximum due to plasmonic resonance (PR) and the coupling between the incident light and the plasmonic metasurface.

Skin-Derived C-Terminal Filaggrin-2 Fragments Are Pseudomonas aeruginosa-Directed Antimicrobials Targeting Bacterial Replication.

Directory of Open Access Journals (Sweden)

Britta Hansmann

2015-09-01

Full Text Available Soil- and waterborne bacteria such as Pseudomonas aeruginosa are constantly challenging body surfaces. Since infections of healthy skin are unexpectedly rare, we hypothesized that the outermost epidermis, the stratum corneum, and sweat glands directly control the growth of P. aeruginosa by surface-provided antimicrobials. Due to its high abundance in the upper epidermis and eccrine sweat glands, filaggrin-2 (FLG2, a water-insoluble 248 kDa S100 fused-type protein, might possess these innate effector functions. Indeed, recombinant FLG2 C-terminal protein fragments display potent antimicrobial activity against P. aeruginosa and other Pseudomonads. Moreover, upon cultivation on stratum corneum, P. aeruginosa release FLG2 C-terminus-containing FLG2 fragments from insoluble material, indicating liberation of antimicrobially active FLG2 fragments by the bacteria themselves. Analyses of the underlying antimicrobial mechanism reveal that FLG2 C-terminal fragments do not induce pore formation, as known for many other antimicrobial peptides, but membrane blebbing, suggesting an alternative mode of action. The association of the FLG2 fragment with the inner membrane of treated bacteria and its DNA-binding implicated an interference with the bacterial replication that was confirmed by in vitro and in vivo replication assays. Probably through in situ-activation by soil- and waterborne bacteria such as Pseudomonads, FLG2 interferes with the bacterial replication, terminates their growth on skin surface and thus may contributes to the skin's antimicrobial defense shield. The apparent absence of FLG2 at certain body surfaces, as in the lung or of burned skin, would explain their higher susceptibility towards Pseudomonas infections and make FLG2 C-terminal fragments and their derivatives candidates for new Pseudomonas-targeting antimicrobials.

Skin-Derived C-Terminal Filaggrin-2 Fragments Are Pseudomonas aeruginosa-Directed Antimicrobials Targeting Bacterial Replication.

Science.gov (United States)

Hansmann, Britta; Schröder, Jens-Michael; Gerstel, Ulrich

2015-09-01

Soil- and waterborne bacteria such as Pseudomonas aeruginosa are constantly challenging body surfaces. Since infections of healthy skin are unexpectedly rare, we hypothesized that the outermost epidermis, the stratum corneum, and sweat glands directly control the growth of P. aeruginosa by surface-provided antimicrobials. Due to its high abundance in the upper epidermis and eccrine sweat glands, filaggrin-2 (FLG2), a water-insoluble 248 kDa S100 fused-type protein, might possess these innate effector functions. Indeed, recombinant FLG2 C-terminal protein fragments display potent antimicrobial activity against P. aeruginosa and other Pseudomonads. Moreover, upon cultivation on stratum corneum, P. aeruginosa release FLG2 C-terminus-containing FLG2 fragments from insoluble material, indicating liberation of antimicrobially active FLG2 fragments by the bacteria themselves. Analyses of the underlying antimicrobial mechanism reveal that FLG2 C-terminal fragments do not induce pore formation, as known for many other antimicrobial peptides, but membrane blebbing, suggesting an alternative mode of action. The association of the FLG2 fragment with the inner membrane of treated bacteria and its DNA-binding implicated an interference with the bacterial replication that was confirmed by in vitro and in vivo replication assays. Probably through in situ-activation by soil- and waterborne bacteria such as Pseudomonads, FLG2 interferes with the bacterial replication, terminates their growth on skin surface and thus may contributes to the skin's antimicrobial defense shield. The apparent absence of FLG2 at certain body surfaces, as in the lung or of burned skin, would explain their higher susceptibility towards Pseudomonas infections and make FLG2 C-terminal fragments and their derivatives candidates for new Pseudomonas-targeting antimicrobials.

SSC Diversity Receiver over Correlated Fading Channels in the Presence of Cochannel Interference

Directory of Open Access Journals (Sweden)

Panić StefanR

2010-01-01

Full Text Available This paper studies the performances of a dual-branch switched-and-stay combining (SSC diversity receiver, operating over correlated fading in the presence of cochannel interference (CCI. Very useful, novel, infinite series expressions are obtained for the output signal to interference ratio's (SIR's probability density function (PDF and cumulative distribution function (CDF. The performance analysis is based on an outage probability (OP and an average bit error probability (ASEP criteria. ASEP is efficiently evaluated for modulation schemes such as noncoherent frequency-shift keying (NCFSK and binary differentially phase-shift keying (BDPSK. The effects of various parameters, such as input SIR unbalance, the level of correlation between received desired signals and interferences, nonlinearity of the environment, and fading severity on systems performances are graphically presented and analyzed.

Nordihydroguaiaretic acid (NDGA) inhibits replication and viral morphogenesis of dengue virus.

Science.gov (United States)

Soto-Acosta, Rubén; Bautista-Carbajal, Patricia; Syed, Gulam H; Siddiqui, Aleem; Del Angel, Rosa M

2014-09-01

Dengue is the most common mosquito borne viral disease in humans. The infection with any of the 4 dengue virus serotypes (DENV) can either be asymptomatic or manifest in two clinical forms, the mild dengue fever or the more severe dengue hemorrhagic fever that may progress into dengue shock syndrome. A DENV replicative cycle relies on host lipid metabolism; specifically, DENV infection modulates cholesterol and fatty acid synthesis, generating a lipid-enriched cellular environment necessary for viral replication. Thus, the aim of this work was to evaluate the anti-DENV effect of the Nordihydroguaiaretic acid (NDGA), a hypolipidemic agent with antioxidant and anti-inflammatory properties. A dose-dependent inhibition in viral yield and NS1 secretion was observed in supernatants of infected cells treated for 24 and 48 h with different concentrations of NDGA. To evaluate the effect of NDGA in DENV replication, a DENV4 replicon transfected Vero cells were treated with different concentrations of NDGA. NDGA treatment significantly reduced DENV replication, reiterating the importance of lipids in viral replication. NDGA treatment also led to reduction in number of lipid droplets (LDs), the neutral lipid storage organelles involved in DENV morphogenesis that are known to increase in number during DENV infection. Furthermore, NDGA treatment resulted in dissociation of the C protein from LDs. Overall our results suggest that NDGA inhibits DENV infection by targeting genome replication and viral assembly. Copyright © 2014 Elsevier B.V. All rights reserved.

Error rates of a full-duplex system over EGK fading channels subject to laplacian interference

KAUST Repository

Soury, Hamza

2017-07-31

This paper develops a mathematical paradigm to study downlink error rates and throughput for half-duplex (HD) terminals served by a full-duplex (FD) base station (BS). Particularly, we study the dominant intra-cell interferer problem that appears between HD users scheduled on the same FD-channel. The distribution of the dominant interference is first characterized via its distribution function, which is derived in closed-form. Assuming Nakagami-m fading, the probability of error for different modulation schemes is studied and a unified closed-form expression for the average symbol error rate is derived. To this end, we show the effective downlink throughput gain, harvested by employing FD communication at a BS that serves HD users, as a function of the signal-to-interference-ratio when compared to an idealized HD interference and noise free BS operation.

Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis

Science.gov (United States)

Hua, Hui; Namdar, Mandana; Ganier, Olivier; Gregan, Juraj; Méchali, Marcel; Kearsey, Stephen E.

2013-01-01

Meiosis involves two successive rounds of chromosome segregation without an intervening S phase. Exit from meiosis I is distinct from mitotic exit, in that replication origins are not licensed by Mcm2-7 chromatin binding, but spindle disassembly occurs during a transient interphase-like state before meiosis II. The absence of licensing is assumed to explain the block to DNA replication, but this has not been formally tested. Here we attempt to subvert this block by expressing the licensing control factors Cdc18 and Cdt1 during the interval between meiotic nuclear divisions. Surprisingly, this leads only to a partial round of DNA replication, even when these factors are overexpressed and effect clear Mcm2-7 chromatin binding. Combining Cdc18 and Cdt1 expression with modulation of cyclin-dependent kinase activity, activation of Dbf4-dependent kinase, or deletion of the Spd1 inhibitor of ribonucleotide reductase has little additional effect on the extent of DNA replication. Single-molecule analysis indicates this partial round of replication results from inefficient progression of replication forks, and thus both initiation and elongation replication steps may be inhibited in late meiosis. In addition, DNA replication or damage during the meiosis I–II interval fails to arrest meiotic progress, suggesting absence of checkpoint regulation of meiosis II entry. PMID:23303250

The stress granule component TIA-1 binds tick-borne encephalitis virus RNA and is recruited to perinuclear sites of viral replication to inhibit viral translation.

Science.gov (United States)

Albornoz, Amelina; Carletti, Tea; Corazza, Gianmarco; Marcello, Alessandro

2014-06-01

, (ii) demonstrates that TIAR behaves like TIA-1 as an inhibitor of viral replication using an RNA interference (RNAi) approach in human cells that contradicts the previous hypothesis based on mouse embryonic fibroblast (MEF) knockouts only, (iii) demonstrates that tick-borne encephalitis virus (TBEV) is capable of inducing bona fide G3BP1/eIF3/eIF4B-positive stress granules, (iv) demonstrates a differential phenotype of stress response proteins following viral infection, and (v) implicates TIA-1 in viral translation and as a modulator of TBEV replication. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Replicative Intermediates of Human Papillomavirus Type 11 in Laryngeal Papillomas: Site of Replication Initiation and Direction of Replication

Science.gov (United States)

Auborn, K. J.; Little, R. D.; Platt, T. H. K.; Vaccariello, M. A.; Schildkraut, C. L.

1994-07-01

We have examined the structures of replication intermediates from the human papillomavirus type 11 genome in DNA extracted from papilloma lesions (laryngeal papillomas). The sites of replication initiation and termination utilized in vivo were mapped by using neutral/neutral and neutral/alkaline two-dimensional agarose gel electrophoresis methods. Initiation of replication was detected in or very close to the upstream regulatory region (URR; the noncoding, regulatory sequences upstream of the open reading frames in the papillomavirus genome). We also show that replication forks proceed bidirectionally from the origin and converge 180circ opposite the URR. These results demonstrate the feasibility of analysis of replication of viral genomes directly from infected tissue.

Inhibition of spring viraemia of carp virus replication in an Epithelioma papulosum cyprini cell line by RNAi

Science.gov (United States)

Gotesman, M; Soliman, H; Besch, R; El-Matbouli, M

2015-01-01

Spring viraemia of carp virus (SVCV) is an aetiological agent of a serious disease affecting carp farms in Europe and is a member of the Rhabdoviridae family of viruses. The genome of SVCV codes for five proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and RNA-dependent RNA polymerase (L). RNA-mediated interference (RNAi) by small interfering RNAs (siRNAs) is a powerful tool to inhibit gene transcription and is used to study genes important for viral replication. In previous studies regarding another member of Rhabdoviridae, siRNA inhibition of the rabies virus nucleoprotein gene provided in vitro and in vivo protection against rabies. In this study, synthetic siRNA molecules were designed to target SVCV-N and SVCV-P transcripts to inhibit SVCV replication and were tested in an epithelioma papulosum cyprini (EPC) cell line. Inhibition of gene transcription was measured by real-time quantitative reverse-transcription PCR (RT-qPCR). The efficacy of using siRNA for inhibition of viral replication was analysed by RT-qPCR measurement of a reporter gene (glycoprotein) expression and by virus endpoint titration. Inhibition of nucleoprotein and phosphoprotein gene expression by siRNA reduced SVCV replication. However, use of tandem siRNAs that target phosphoprotein and nucleoprotein worked best at reducing SVCV replication. PMID:24460815

Engineered disease resistance in cotton using RNA-interference to knock down cotton leaf curl kokhran virus-Burewala and cotton leaf curl Multan betasatellite

Science.gov (United States)

Cotton Leaf Curl virus Disease (CLCuD) has caused enormous losses in cotton (Gossypium hirsutum) production in Pakistan. RNA interference (RNAi) is an emerging technique that could knock out CLCuD by targeting different regions of the pathogen genome that are important for replication, transcription...

CRISPR/Cas9-mediated viral interference in plants

KAUST Repository

Ali, Zahir

2015-11-11

Background The CRISPR/Cas9 system provides bacteria and archaea with molecular immunity against invading phages and conjugative plasmids. Recently, CRISPR/Cas9 has been used for targeted genome editing in diverse eukaryotic species. Results In this study, we investigate whether the CRISPR/Cas9 system could be used in plants to confer molecular immunity against DNA viruses. We deliver sgRNAs specific for coding and non-coding sequences of tomato yellow leaf curl virus (TYLCV) into Nicotiana benthamiana plants stably overexpressing the Cas9 endonuclease, and subsequently challenge these plants with TYLCV. Our data demonstrate that the CRISPR/Cas9 system targeted TYLCV for degradation and introduced mutations at the target sequences. All tested sgRNAs exhibit interference activity, but those targeting the stem-loop sequence within the TYLCV origin of replication in the intergenic region (IR) are the most effective. N. benthamiana plants expressing CRISPR/Cas9 exhibit delayed or reduced accumulation of viral DNA, abolishing or significantly attenuating symptoms of infection. Moreover, this system could simultaneously target multiple DNA viruses. Conclusions These data establish the efficacy of the CRISPR/Cas9 system for viral interference in plants, thereby extending the utility of this technology and opening the possibility of producing plants resistant to multiple viral infections.

Sequence analysis of malacoherpesvirus proteins: Pan-herpesvirus capsid module and replication enzymes with an ancient connection to "Megavirales".

Science.gov (United States)

Mushegian, Arcady; Karin, Eli Levy; Pupko, Tal

2018-01-01

The order Herpesvirales includes animal viruses with large double-strand DNA genomes replicating in the nucleus. The main capsid protein in the best-studied family Herpesviridae contains a domain with HK97-like fold related to bacteriophage head proteins, and several virion maturation factors are also homologous between phages and herpesviruses. The origin of herpesvirus DNA replication proteins is less well understood. While analyzing the genomes of herpesviruses in the family Malacohepresviridae, we identified nearly 30 families of proteins conserved in other herpesviruses, including several phage-related domains in morphogenetic proteins. Herpesvirus DNA replication factors have complex evolutionary history: some are related to cellular proteins, but others are closer to homologs from large nucleocytoplasmic DNA viruses. Phylogenetic analyses suggest that the core replication machinery of herpesviruses may have been recruited from the same pool as in the case of other large DNA viruses of eukaryotes. Published by Elsevier Inc.

Rotavirus replication is correlated with S/G2 interphase arrest of the host cell cycle.

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Selene Glück

Full Text Available In infected cells rotavirus (RV replicates in viroplasms, cytosolic structures that require a stabilized microtubule (MT network for their assembly, maintenance of the structure and perinuclear localization. Therefore, we hypothesized that RV could interfere with the MT-breakdown that takes place in mitosis during cell division. Using synchronized RV-permissive cells, we show that RV infection arrests the cell cycle in S/G2 phase, thus favoring replication by improving viroplasms formation, viral protein translation, and viral assembly. The arrest in S/G2 phase is independent of the host or viral strain and relies on active RV replication. RV infection causes cyclin B1 down-regulation, consistent with blocking entry into mitosis. With the aid of chemical inhibitors, the cytoskeleton network was linked to specific signaling pathways of the RV-induced cell cycle arrest. We found that upon RV infection Eg5 kinesin was delocalized from the pericentriolar region to the viroplasms. We used a MA104-Fucci system to identify three RV proteins (NSP3, NSP5, and VP2 involved in cell cycle arrest in the S-phase. Our data indicate that there is a strong correlation between the cell cycle arrest and RV replication.

Trait anxiety modulates fronto-limbic processing of emotional interference in Borderline Personality Disorder

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Jana eHoltmann

2013-03-01

Full Text Available Previous studies of cognitive alterations in Borderline Personality Disorder (BPD have yielded conflicting results. Given that a core feature of BPD is affective instability, which is characterized by emotional hyperreactivity and deficits in emotion regulation, it seems conceivable that short-lasting emotional distress might exert temporary detrimental effects on cognitive performance. Here we used functional magnetic resonance imaging (fMRI to investigate how task-irrelevant emotional stimuli (fearful faces affect performance and fronto-limbic neural activity patterns during attention-demanding cognitive processing in 16 female, unmedicated BPD patients relative to 24 age-matched healthy controls. In a modified flanker task, emotionally negative, socially salient pictures (fearful versus neutral faces were presented as distracters in the background. Patients, but not controls, showed an atypical response pattern of the right amygdala with increased activation during emotional interference in the (difficult incongruent flanker condition, but emotion-related amygdala deactivation in the congruent condition. A direct comparison of the emotional conditions between the two groups revealed that the strongest diagnosis-related differences could be observed in the dorsal and, to a lesser extent, also in the rostral anterior cingulate cortex (dACC, rACC where patients exhibited an increased neural response to emotional relative to neutral distracters. Moreover, in the incongruent condition, both the dACC and rACC fMRI responses during emotional interference were negatively correlated with trait anxiety in the patients, but not in the healthy controls. As higher trait anxiety was also associated with longer reaction times in the BPD patients, we suggest that in BPD patients the ACC might mediate compensatory cognitive processes during emotional interference and that such neurocognitive compensation that can be adversely affected by high levels of

Dynamic optical arbitrary waveform shaping based on cascaded optical modulators of single FBG.

Science.gov (United States)

Chen, Jingyuan; Li, Peili

2015-08-10

A dynamic optical arbitrary waveform generation (O-AWG) with amplitude and phase independently controlled in optical modulators of single fiber Bragg Grating (FBG) has been proposed. This novel scheme consists of several optical modulators. In the optical modulator (O-MOD), a uniform FBG is used to filter spectral component of the input signal. The amplitude is controlled by fiber stretcher (FS) in Mach-Zehnder interference (MZI) structure through interference of two MZI arms. The phase is manipulated via the second FS in the optical modulator. This scheme is investigated by simulation. Consequently, optical pulse trains with different waveforms as well as pulse trains with nonuniform pulse intensity, pulse spacing and pulse width within each period are obtained through FSs adjustment to alter the phase shifts of signal in each O-MOD.

Optical image encryption with silhouette removal based on interference and phase blend processing

Science.gov (United States)

Wang, Qu

2012-10-01

To completely eliminate the silhouette problem that inherently exists in the earlier interference-based encryption scheme with two phase-only masks (POMs), we propose a simple new encryption method based on optical interference of one random POM and two analytically obtained POMs. Different from the previous methods which require time-consuming iterative computation or postprocessing of the POMs for silhouette removal, our method can resolve the problem during the production of the POMs based on interference principle. Information associated with the original image is smoothed away by modulation of the random POM. Illegal deciphers cannot retrieve the primitive image using only one or two of the POMs. Incorporated with the linear phase blend operation, our method can provide higher robustness against brute force attacks. Simulation results are presented to support the validity and feasibility of our method.

Quantum interference of ballistic carriers in one-dimensional semiconductor rings

International Nuclear Information System (INIS)

Bagraev, N.T.; Buravlev, A.D.; Klyachkin, L.E.; Malyarenko, A.M.; Ivanov, V.K.; Rykov, S.A.; Shelykh, I.A.

2000-01-01

Quantum interference of ballistic carriers has been studied for the first time, using one-dimensional rings formed by quantum wire pairs in self-assembled silicon quantum wells. Energy dependencies of the transmission coefficient is calculated as a function of the length and modulation of the quantum wire pairs separated by a unified drain-source system or the quantum point contacts. The quantum conductance is predicted to be increased by a factor of four using the unified drain-source system as a result of the quantum interference. Theoretical dependencies are revealed by the quantum conductance oscillations created by the deviations of both the drain-source voltage and external magnetic field inside the silicon one-dimensional rings. The results obtained put forward a basis to create the Aharonov-Bohm interferometer using the silicon one-dimensional ring [ru

Fabrication of sub-micrometric metallic hollow-core structures by laser interference lithography

International Nuclear Information System (INIS)

Pérez, Noemí; Tavera, Txaber; Rodríguez, Ainara; Ellman, Miguel; Ayerdi, Isabel; Olaizola, Santiago M.

2012-01-01

Highlights: ► Arrays of hollow-core sub-micrometric structures are fabricated. ► Laser interference lithography is used for the pattering of the resist sacrificial layer. ► The removal of the sacrificial layer gives rise to metallic channels with a maximum crosssectional area of 0.1 μm 2 . ► These structures can be used in nanofluidics. - Abstract: This work presents the fabrication of hollow-core metallic structures with a complete laser interference lithography (LIL) process. A negative photoresist is used as sacrificial layer. It is exposed to the pattern resulting from the interference of two laser beams, which produces a structure of photoresist lines with a period of 600 nm. After development of the resist, platinum is deposited on the samples by DC sputtering and the resist is removed with acetone. The resulting metallic structures consist in a continuous platinum film that replicates the photoresist relief with a hollow core. The cross section of the channels is up to 0.1 μm 2 . The fabricated samples are characterized by FESEM and FIB. This last tool helps to provide a clear picture of the shape and size of the channels. Conveniently dimensioned, this array of metallic submicrometric channels can be used in microfluidic or IC cooling applications.

Intermolecular RNA Recombination Occurs at Different Frequencies in Alternate Forms of Brome Mosaic Virus RNA Replication Compartments

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Hernan Garcia-Ruiz

2018-03-01

Full Text Available Positive-strand RNA viruses replicate their genomes in membrane-bound replication compartments. Brome mosaic virus (BMV replicates in vesicular invaginations of the endoplasmic reticulum membrane. BMV has served as a productive model system to study processes like virus-host interactions, RNA replication and recombination. Here we present multiple lines of evidence showing that the structure of the viral RNA replication compartments plays a fundamental role and that recruitment of parental RNAs to a common replication compartment is a limiting step in intermolecular RNA recombination. We show that a previously defined requirement for an RNA recruitment element on both parental RNAs is not to function as a preferred crossover site, but in order for individual RNAs to be recruited into the replication compartments. Moreover, modulating the form of the replication compartments from spherular vesicles (spherules to more expansive membrane layers increased intermolecular RNA recombination frequency by 200- to 1000-fold. We propose that intermolecular RNA recombination requires parental RNAs to be recruited into replication compartments as monomers, and that recruitment of multiple RNAs into a contiguous space is much more common for layers than for spherules. These results could explain differences in recombination frequencies between viruses that replicate in association with smaller spherules versus larger double-membrane vesicles and convoluted membranes.

Suppression of Rac1 Signaling by Influenza A Virus NS1 Facilitates Viral Replication

Science.gov (United States)

Jiang, Wei; Sheng, Chunjie; Gu, Xiuling; Liu, Dong; Yao, Chen; Gao, Shijuan; Chen, Shuai; Huang, Yinghui; Huang, Wenlin; Fang, Min

2016-01-01

Influenza A virus (IAV) is a major human pathogen with the potential to become pandemic. IAV contains only eight RNA segments; thus, the virus must fully exploit the host cellular machinery to facilitate its own replication. In an effort to comprehensively characterize the host machinery taken over by IAV in mammalian cells, we generated stable A549 cell lines with over-expression of the viral non-structural protein (NS1) to investigate the potential host factors that might be modulated by the NS1 protein. We found that the viral NS1 protein directly interacted with cellular Rac1 and facilitated viral replication. Further research revealed that NS1 down-regulated Rac1 activity via post-translational modifications. Therefore, our results demonstrated that IAV blocked Rac1-mediated host cell signal transduction through the NS1 protein to facilitate its own replication. Our findings provide a novel insight into the mechanism of IAV replication and indicate new avenues for the development of potential therapeutic targets. PMID:27869202

Stroop Interference in a Delayed Match-to-Sample Task: Evidence for Semantic Competition

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Bradley R. Sturz

2013-11-01

Full Text Available Discussions of the source of the Stroop interference effect continue to pervade the literature. Semantic competition posits that interference results from competing semantic activation of word and color dimensions of the stimulus prior to response selection. Response competition posits that interference results from competing responses for articulating the word dimension versus the color dimension at the time of response selection. We embedded Stroop stimuli into a delayed match-to-sample task in an attempt to test semantic and response competition accounts of the interference effect. Participants viewed a sample color word in black or colored fonts that were congruent or incongruent with respect to the color word itself. After a 5s delay, participants were presented with two targets (i.e., a match and a foil and were instructed to select the correct match. We probed each dimension independently during target presentations via color targets (i.e., two colors or word targets (i.e., two words and manipulated whether the semantic content of the foil was related to the semantic content of the irrelevant sample dimension (e.g., word sample red in blue font with the word red as the match and the word blue as the foil. We provide evidence for Stroop interference such that response times increased for incongruent trials even in the presence of a response option with semantic content unrelated to the semantic content of the irrelevant sample dimension. Accuracy also deteriorated during the related foil trials. A follow-up experiment with a 10s delay between sample and targets replicated the results. Results appear to provide converging evidence for Stroop interference in a delayed match-to-sample task in a manner that is consistent with an explanation based upon semantic competition and inconsistent with an explanation based upon response competition.

Evaluating viral interference between Influenza virus and Newcastle disease virus using real-time reverse transcription–polymerase chain reaction in chicken eggs

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Ge Shengqiang

2012-07-01

Full Text Available Abstract Background Simultaneous and sequential allantoic cavity inoculations of Specific-pathogen-free (SPF chicken eggs with Influenza virus (AIV and Newcastle disease virus (NDV demonstrated that the interaction of AIV and NDV during co-infection was variable. Our research revisited the replication interference potential of AIV and NDV using real-time reverse transcription–polymerase chain reaction (real-time RT-PCR for AIV and NDV to specifically detect the viral genomes in mixed infections. Results Data from this survey showed that when different doses of NDV (Lasota or F48E8 and AIV (F98 or H5N1 were simultaneously inoculated into embryonating chicken eggs (ECE, interference with the growth of NDV occurred, while interference with the growth of AIV did not occur. When equal amount of the two viruses were sequentially employed, the degree of interference was dependent upon the time of superinfection and the virulence of virus. Conclusion AIV have a negative impact on NDV growth if they are inoculated simultaneously or sequentially and that the degree of interference depended upon the quantity and relative virulence of the virus strains used; however, interference with AIV was not observed. Only if NDV were inoculated at an earlier time will NDV able to interfere with the growth of AIV.

Selective post-training time window for memory consolidation interference of cannabidiol into the prefrontal cortex: Reduced dopaminergic modulation and immediate gene expression in limbic circuits.

Science.gov (United States)

Rossignoli, Matheus Teixeira; Lopes-Aguiar, Cleiton; Ruggiero, Rafael Naime; Do Val da Silva, Raquel Araujo; Bueno-Junior, Lezio Soares; Kandratavicius, Ludmyla; Peixoto-Santos, José Eduardo; Crippa, José Alexandre; Cecilio Hallak, Jaime Eduardo; Zuardi, Antonio Waldo; Szawka, Raphael Escorsim; Anselmo-Franci, Janete; Leite, João Pereira; Romcy-Pereira, Rodrigo Neves

2017-05-14

The prefrontal cortex (PFC), amygdala and hippocampus display a coordinated activity during acquisition of associative fear memories. Evidence indicates that PFC engagement in aversive memory formation does not progress linearly as previously thought. Instead, it seems to be recruited at specific time windows after memory acquisition, which has implications for the treatment of post-traumatic stress disorders. Cannabidiol (CBD), the major non-psychotomimetic phytocannabinoid of the Cannabis sativa plant, is known to modulate contextual fear memory acquisition in rodents. However, it is still not clear how CBD interferes with PFC-dependent processes during post-training memory consolidation. Here, we tested whether intra-PFC infusions of CBD immediately after or 5h following contextual fear conditioning was able to interfere with memory consolidation. Neurochemical and cellular correlates of the CBD treatment were evaluated by the quantification of extracellular levels of dopamine (DA), serotonin, and their metabolites in the PFC and by measuring the cellular expression of activity-dependent transcription factors in cortical and limbic regions. Our results indicate that bilateral intra-PFC CBD infusion impaired contextual fear memory consolidation when applied 5h after conditioning, but had no effect when applied immediately after it. This effect was associated with a reduction in DA turnover in the PFC following retrieval 5days after training. We also observed that post-conditioning infusion of CBD reduced c-fos and zif-268 protein expression in the hippocampus, PFC, and thalamus. Our findings support that CBD interferes with contextual fear memory consolidation by reducing PFC influence on cortico-limbic circuits. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Experimental occlusal interferences. Part III. Mandibular rotations induced by a rigid interference.

Science.gov (United States)

Rassouli, N M; Christensen, L V

1995-10-01

A rigid intercuspal interference (minimum mean height of 0.24 mm) was placed on either the right or left mandibular second premolar and first molar of 12 subjects. During brisk and forceful biting on the interference, rotational electrognathography measured maximum torque of the right and left mandibular condyles in the frontal and horizontal planes of orientation. All subjects showed frontal plan upward rotation (mean of 0.7 degrees) of the mandibular condyle contralateral to the interference. In 33% of the subjects there was no horizontal plane backward rotation. In 58% of the subjects there was horizontal plane backward rotation (mean of 0.5 degrees) of the mandibular condyle ipsilateral to the interference, and in one subject (8%) there was backward horizontal plane rotation (0.1 degree) of the mandibular condyle contralateral to the interference. It was inferred that the masseter muscle, ipsilateral to the interference, generated negative work in order to decelerate frontal plane 'unseating' of the mandibular condyle ipsilateral to the interference. It was inferred that the masseter muscle, contralateral to the interference, produced positive work in order to accelerate frontal plane 'seating' of the mandibular condyle contralateral to the interference. Finally, it was speculated that the impact forces of frontal plane 'seating' of the mandibular condyle, contralateral to the interference, might lead to 'vacuum sticking' of the temporomandibular joint disc because of the formation of negative hydrostatic pressures.

Experimental occlusal interferences. Part II. Masseteric EMG responses to an intercuspal interference.

Science.gov (United States)

Christensen, L V; Rassouli, N M

1995-07-01

In 12 subjects, a rigid unilateral intercuspal interference (minimum mean height of 0.24 mm) was placed on either the right or left mandibular second premolar and first molar (sagittal physiological equilibrium point of the hemimandibular dental arch). During brisk and forceful clenching on the interference, bipolar surface electromyograms were obtained from the right and left masseter muscles. On the side opposite the interference, myoelectric clenching activity was significantly reduced. Correlation analyses showed that the interference elicited a non-linear (complex) co-ordination of the amplitude, but not the duration, of bilateral masseteric clenching activity, i.e. frequently there was significant motor facilitation on the side of the interference, and significant motor inhibition on the side opposite the interference. Theoretical considerations predicted that brief clenching on the interference would easily lead to frontal plane rotatory motions of the mandible which, indeed, occurred clinically.

Repair replication in replicating and nonreplicating DNA after irradiation with uv light

Energy Technology Data Exchange (ETDEWEB)

Slor, H.; Cleaver, J.E.

1978-06-01

Ultraviolet light induces more pyrimidine dimers and more repair replication in DNA that replicates within 2 to 3 h of irradiation than in DNA that does not replicate during this period. This difference may be due to special conformational changes in DNA and chromatin that might be associated with semiconservative DNA replication.

IETS and quantum interference

DEFF Research Database (Denmark)

Jørgensen, Jacob Lykkebo; Gagliardi, Alessio; Pecchia, Alessandro

2014-01-01

Destructive quantum interference in single molecule electronics is an intriguing phenomenon; however, distinguishing quantum interference effects from generically low transmission is not trivial. In this paper, we discuss how quantum interference effects in the transmission lead to either low...... suppressed when quantum interference effects dominate. That is, we expand the understanding of propensity rules in inelastic electron tunneling spectroscopy to molecules with destructive quantum interference....

Protein arginine methyltransferase 1 regulates herpes simplex virus replication through ICP27 RGG-box methylation

Energy Technology Data Exchange (ETDEWEB)

Yu, Jungeun; Shin, Bongjin; Park, Eui-Soon; Yang, Sujeong; Choi, Seunga [Department of Microbiology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); BK21 Bio Brain Center, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); Kang, Misun [Department of Microbiology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); Rho, Jaerang, E-mail: jrrho@cnu.ac.kr [Department of Microbiology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); BK21 Bio Brain Center, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); GRAST, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of)

2010-01-01

Protein arginine methylation is involved in viral infection and replication through the modulation of diverse cellular processes including RNA metabolism, cytokine signaling, and subcellular localization. It has been suggested previously that the protein arginine methylation of the RGG-box of ICP27 is required for herpes simplex virus type-1 (HSV-1) viral replication and gene expression in vivo. However, a cellular mediator for this process has not yet been identified. In our current study, we show that the protein arginine methyltransferase 1 (PRMT1) is a cellular mediator of the arginine methylation of ICP27 RGG-box. We generated arginine substitution mutants in this domain and examined which arginine residues are required for methylation by PRMT1. R138, R148 and R150 were found to be the major sites of this methylation but additional arginine residues serving as minor methylation sites are still required to sustain the fully methylated form of ICP27 RGG. We also demonstrate that the nuclear foci-like structure formation, SRPK interactions, and RNA-binding activity of ICP27 are modulated by the arginine methylation of the ICP27 RGG-box. Furthermore, HSV-1 replication is inhibited by hypomethylation of this domain resulting from the use of general PRMT inhibitors or arginine mutations. Our data thus suggest that the PRMT1 plays a key role as a cellular regulator of HSV-1 replication through ICP27 RGG-box methylation.

Phosphatidic acid produced by phospholipase D promotes RNA replication of a plant RNA virus.

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Kiwamu Hyodo

2015-05-01

Full Text Available Eukaryotic positive-strand RNA [(+RNA] viruses are intracellular obligate parasites replicate using the membrane-bound replicase complexes that contain multiple viral and host components. To replicate, (+RNA viruses exploit host resources and modify host metabolism and membrane organization. Phospholipase D (PLD is a phosphatidylcholine- and phosphatidylethanolamine-hydrolyzing enzyme that catalyzes the production of phosphatidic acid (PA, a lipid second messenger that modulates diverse intracellular signaling in various organisms. PA is normally present in small amounts (less than 1% of total phospholipids, but rapidly and transiently accumulates in lipid bilayers in response to different environmental cues such as biotic and abiotic stresses in plants. However, the precise functions of PLD and PA remain unknown. Here, we report the roles of PLD and PA in genomic RNA replication of a plant (+RNA virus, Red clover necrotic mosaic virus (RCNMV. We found that RCNMV RNA replication complexes formed in Nicotiana benthamiana contained PLDα and PLDβ. Gene-silencing and pharmacological inhibition approaches showed that PLDs and PLDs-derived PA are required for viral RNA replication. Consistent with this, exogenous application of PA enhanced viral RNA replication in plant cells and plant-derived cell-free extracts. We also found that a viral auxiliary replication protein bound to PA in vitro, and that the amount of PA increased in RCNMV-infected plant leaves. Together, our findings suggest that RCNMV hijacks host PA-producing enzymes to replicate.

Human Parvovirus B19 Utilizes Cellular DNA Replication Machinery for Viral DNA Replication.

Science.gov (United States)

Zou, Wei; Wang, Zekun; Xiong, Min; Chen, Aaron Yun; Xu, Peng; Ganaie, Safder S; Badawi, Yomna; Kleiboeker, Steve; Nishimune, Hiroshi; Ye, Shui Qing; Qiu, Jianming

2018-03-01

Human parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral DNA replication. However, it is not clear exactly which cellular factors are employed by this single-stranded DNA virus. Here, we used microarrays to systematically analyze the dynamic transcriptome of EPCs infected with B19V. We found that DNA metabolism, DNA replication, DNA repair, DNA damage response, cell cycle, and cell cycle arrest pathways were significantly regulated after B19V infection. Confocal microscopy analyses revealed that most cellular DNA replication proteins were recruited to the centers of viral DNA replication, but not the DNA repair DNA polymerases. Our results suggest that DNA replication polymerase δ and polymerase α are responsible for B19V DNA replication by knocking down its expression in EPCs. We further showed that although RPA32 is essential for B19V DNA replication and the phosphorylated forms of RPA32 colocalized with the replicating viral genomes, RPA32 phosphorylation was not necessary for B19V DNA replication. Thus, this report provides evidence that B19V uses the cellular DNA replication machinery for viral DNA replication. IMPORTANCE Human parvovirus B19 (B19V) infection can cause transient aplastic crisis, persistent viremia, and pure red cell aplasia. In fetuses, B19V infection can result in nonimmune hydrops fetalis and fetal death. These clinical manifestations of B19V infection are a direct outcome of the death of human erythroid progenitors that host B19V replication. B19V infection induces a DNA damage response that is important for cell cycle arrest at late S phase. Here, we analyzed dynamic changes in cellular gene expression and found that DNA metabolic processes are tightly regulated during B19V infection. Although genes involved in cellular DNA replication were downregulated overall, the cellular DNA replication machinery was tightly

MOF Suppresses Replication Stress and Contributes to Resolution of Stalled Replication Forks.

Science.gov (United States)

Singh, Dharmendra Kumar; Pandita, Raj K; Singh, Mayank; Chakraborty, Sharmistha; Hambarde, Shashank; Ramnarain, Deepti; Charaka, Vijaya; Ahmed, Kazi Mokim; Hunt, Clayton R; Pandita, Tej K

2018-03-15

The human MOF (hMOF) protein belongs to the MYST family of histone acetyltransferases and plays a critical role in transcription and the DNA damage response. MOF is essential for cell proliferation; however, its role during replication and replicative stress is unknown. Here we demonstrate that cells depleted of MOF and under replicative stress induced by cisplatin, hydroxyurea, or camptothecin have reduced survival, a higher frequency of S-phase-specific chromosome damage, and increased R-loop formation. MOF depletion decreased replication fork speed and, when combined with replicative stress, also increased stalled replication forks as well as new origin firing. MOF interacted with PCNA, a key coordinator of replication and repair machinery at replication forks, and affected its ubiquitination and recruitment to the DNA damage site. Depletion of MOF, therefore, compromised the DNA damage repair response as evidenced by decreased Mre11, RPA70, Rad51, and PCNA focus formation, reduced DNA end resection, and decreased CHK1 phosphorylation in cells after exposure to hydroxyurea or cisplatin. These results support the argument that MOF plays an important role in suppressing replication stress induced by genotoxic agents at several stages during the DNA damage response. Copyright © 2018 American Society for Microbiology.

Functional connections between activated and deactivated brain regions mediate emotional interference during externally directed cognition.

Science.gov (United States)

Di Plinio, Simone; Ferri, Francesca; Marzetti, Laura; Romani, Gian Luca; Northoff, Georg; Pizzella, Vittorio

2018-04-24

Recent evidence shows that task-deactivations are functionally relevant for cognitive performance. Indeed, higher cognitive engagement has been associated with higher suppression of activity in task-deactivated brain regions - usually ascribed to the Default Mode Network (DMN). Moreover, a negative correlation between these regions and areas actively engaged by the task is associated with better performance. DMN regions show positive modulation during autobiographical, social, and emotional tasks. However, it is not clear how processing of emotional stimuli affects the interplay between the DMN and executive brain regions. We studied this interplay in an fMRI experiment using emotional negative stimuli as distractors. Activity modulations induced by the emotional interference of negative stimuli were found in frontal, parietal, and visual areas, and were associated with modulations of functional connectivity between these task-activated areas and DMN regions. A worse performance was predicted both by lower activity in the superior parietal cortex and higher connectivity between visual areas and frontal DMN regions. Connectivity between right inferior frontal gyrus and several DMN regions in the left hemisphere was related to the behavioral performance. This relation was weaker in the negative than in the neutral condition, likely suggesting less functional inhibitions of DMN regions during emotional processing. These results show that both executive and DMN regions are crucial for the emotional interference process and suggest that DMN connections are related to the interplay between externally-directed and internally-focused processes. Among DMN regions, superior frontal gyrus may be a key node in regulating the interference triggered by emotional stimuli. © 2018 Wiley Periodicals, Inc.

Database Replication

CERN Document Server

Kemme, Bettina

2010-01-01

Database replication is widely used for fault-tolerance, scalability and performance. The failure of one database replica does not stop the system from working as available replicas can take over the tasks of the failed replica. Scalability can be achieved by distributing the load across all replicas, and adding new replicas should the load increase. Finally, database replication can provide fast local access, even if clients are geographically distributed clients, if data copies are located close to clients. Despite its advantages, replication is not a straightforward technique to apply, and

Codebook-based interference alignment for uplink MIMO interference channels

KAUST Repository

Lee, Hyun Ho; Park, Kihong; Ko, Youngchai; Alouini, Mohamed-Slim

2014-01-01

In this paper, we propose a codebook-based interference alignment (IA) scheme in the constant multiple-input multipleoutput (MIMO) interference channel especially for the uplink scenario. In our proposed scheme, we assume cooperation among base

Low level perceptual, not attentional, processes modulate distractor interference in high perceptual load displays: evidence from neglect/extinction.

Science.gov (United States)

Mevorach, Carmel; Tsal, Yehoshua; Humphreys, Glyn W

2014-01-10

According to perceptual load theory (Lavie, 2005) distractor interference is determined by the availability of attentional resources. If target processing does not exhaust resources (with low perceptual load) distractor processing will take place resulting in interference with a primary task; however, when target processing uses-up attentional capacity (with high perceptual load) interference can be avoided. An alternative account (Tsal and Benoni, 2010a) suggests that perceptual load effects can be based on distractor dilution by the mere presence of additional neutral items in high-load displays so that the effect is not driven by the amount of attention resources required for target processing. Here we tested whether patients with unilateral neglect or extinction would show dilution effects from neutral items in their contralesional (neglected/extinguished) field, even though these items do not impose increased perceptual load on the target and at the same time attract reduced attentional resources compared to stimuli in the ipsilesional field. Thus, such items do not affect the amount of attention resources available for distractor processing. We found that contralesional neutral elements can eliminate distractor interference as strongly as centrally presented ones in neglect/extinction patients, despite contralesional items being less well attended. The data are consistent with an account in terms of perceptual dilution of distracters rather than available resources for distractor processing. We conclude that distractor dilution can underlie the elimination of distractor interference in visual displays.

Low level perceptual, not attentional, processes modulate distractor interference in high perceptual Load displays: evidence from neglect/extinction

Directory of Open Access Journals (Sweden)

Carmel eMevorach

2014-01-01

Full Text Available According to perceptual load theory (Lavie, 2005 distractor interference is determined by the availability of attentional resources. If target processing does not exhaust resources (with low perceptual load distractor processing will take place resulting in interference with a primary task; however when target processing uses-up attentional capacity (with high perceptual load interference can be avoided. An alternative account (Tsal & Benoni, 2010 suggests that perceptual load effects can be based on distractor dilution by the mere presence of additional neutral items in high load displays so that the effect is not driven by the amount of attention resources required for target processing. Here we tested whether patients with unilateral neglect or extinction would show dilution effects from neutral items in their contralesional (neglected/extinguished field, even though these items do not impose increased perceptual load on the target and at the same time attract reduced attentional resources compared to stimuli in the ipsilesional field. Thus, such items do not affect the amount of attention resources available for distractor processing. We found that contralesional neutral elements can eliminate distractor interference as strongly as centrally presented ones in neglect/extinction patients, despite contralesional items being less well attended. The data are consistent with an account in terms of perceptual dilution of distracters rather than available resources for distractor processing. We conclude that distractor dilution can underlie the elimination of distractor interference in visual displays.

Index modulation for 5G wireless communications

CERN Document Server

Wen, Miaowen; Yang, Liuqing

2017-01-01

This book presents a thorough examination of index modulation, an emerging 5G modulation technique. It includes representative transmitter and receiver design, optimization, and performance analysis of index modulation in various domains. First, the basic spatial modulation system for the spatial domain is introduced. Then, the development of a generalized pre-coding aided quadrature spatial modulation system as well as a virtual spatial modulation system are presented. For the space-time domain, a range of differential spatial modulation systems are examined, along with the pre-coding design. Both basic and enhanced index modulated OFDM systems for the frequency domain are discussed, focusing on the verification of their strong capabilities in inter-carrier interference mitigation. Finally, key open problems are highlighted and future research directions are considered. Designed for researchers and professionals, this book is essential for anyone working in communications networking, 5G, and system design. A...

Modulation of mutagenesis in eukaryotes by DNA replication fork dynamics and quality of nucleotide pools

Science.gov (United States)

Waisertreiger, Irina S.-R.; Liston, Victoria G.; Menezes, Miriam R.; Kim, Hyun-Min; Lobachev, Kirill S.; Stepchenkova, Elena I.; Tahirov, Tahir H.; Rogozin, Igor B.; Pavlov, Youri. I.

2014-01-01

The rate of mutations in eukaryotes depends on a plethora of factors and is not immediately derived from the fidelity of DNA polymerases (Pols). Replication of chromosomes containing the anti-parallel strands of duplex DNA occurs through the copying of leading and lagging strand templates by a trio of Pols α, δ and ε, with the assistance of Pol ζ and Y-family Pols at difficult DNA template structures or sites of DNA damage. The parameters of the synthesis at a given location are dictated by the quality and quantity of nucleotides in the pools, replication fork architecture, transcription status, regulation of Pol switches, and structure of chromatin. The result of these transactions is a subject of survey and editing by DNA repair. PMID:23055184

Electromagnetic Interference Assessment of CDMA and GSM Wireless Phones to Aircraft Navigation Radios

Science.gov (United States)

Ely, Jay J.; Nguyen, Truong X.; Koppen, Sandra V.; Salud, M. Theresa

2002-01-01

To address the concern for cellular phone electromagnetic interference (EMI) to aircraft radios, a radiated emission measurement process for CDMA (IS-95) and GSM (ETSI GSM 11.22) wireless handsets was developed. Spurious radiated emissions were efficiently characterized from devices tested in either a semi-anechoic or reverberation chamber, in terms of effective isotropic radiated power. Eight representative handsets (4 GSM, 4 CDMA) were commanded to operate while varying their radio transmitter parameters (power, modulation, etc.). This report provides a detailed description of the measurement process and resulting data, which may subsequently be used by others as a basis of consistent evaluation for cellular/PCS phones, Bluetooth, IEEE802.11b, IEEE802.11a, FRS/GMRS radios, and other portable transmitters. Aircraft interference path loss (IPL) and navigation radio interference threshold data from numerous reference documents, standards, and NASA partnerships were compiled. Using this data, a preliminary risk assessment is provided for CDMA and GSM wireless phone interference to aircraft localizer, Glideslope, VOR, and GPS radio receivers on typical transport airplanes. The report identifies where existing data for device emissions, IPL, and navigation radio interference thresholds needs to be extended for an accurate risk assessment for wireless transmitters in aircraft.

X-irradiation affects all DNA replication intermediates when inhibiting replication initiation

International Nuclear Information System (INIS)

Loenn, U.; Karolinska Hospital, Stockholm

1982-01-01

When a human melanoma line was irradiated with 10 Gy, there was, after 30 to 60 min, a gradual reduction in the DNA replication rate. Ten to twelve hours after the irradiation, the DNA replication had returned to near normal rate. The results showed tht low dose-rate X-irradiation inhibits preferentially the formation of small DNA replication intermediates. There is no difference between the inhibition of these replication intermediates formed only in the irradiated cells and those formed also in untreated cells. (U.K.)

Chromatin Structure and Replication Origins: Determinants Of Chromosome Replication And Nuclear Organization

Science.gov (United States)

Smith, Owen K.; Aladjem, Mirit I.

2014-01-01

The DNA replication program is, in part, determined by the epigenetic landscape that governs local chromosome architecture and directs chromosome duplication. Replication must coordinate with other biochemical processes occurring concomitantly on chromatin, such as transcription and remodeling, to insure accurate duplication of both genetic and epigenetic features and to preserve genomic stability. The importance of genome architecture and chromatin looping in coordinating cellular processes on chromatin is illustrated by two recent sets of discoveries. First, chromatin-associated proteins that are not part of the core replication machinery were shown to affect the timing of DNA replication. These chromatin-associated proteins could be working in concert, or perhaps in competition, with the transcriptional machinery and with chromatin modifiers to determine the spatial and temporal organization of replication initiation events. Second, epigenetic interactions are mediated by DNA sequences that determine chromosomal replication. In this review we summarize recent findings and current models linking spatial and temporal regulation of the replication program with epigenetic signaling. We discuss these issues in the context of the genome’s three-dimensional structure with an emphasis on events occurring during the initiation of DNA replication. PMID:24905010

Inhibition of spring viraemia of carp virus replication in an Epithelioma papulosum cyprini cell line by RNAi.

Science.gov (United States)

Gotesman, M; Soliman, H; Besch, R; El-Matbouli, M

2015-02-01

Spring viraemia of carp virus (SVCV) is an aetiological agent of a serious disease affecting carp farms in Europe and is a member of the Rhabdoviridae family of viruses. The genome of SVCV codes for five proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and RNA-dependent RNA polymerase (L). RNA-mediated interference (RNAi) by small interfering RNAs (siRNAs) is a powerful tool to inhibit gene transcription and is used to study genes important for viral replication. In previous studies regarding another member of Rhabdoviridae, siRNA inhibition of the rabies virus nucleoprotein gene provided in vitro and in vivo protection against rabies. In this study, synthetic siRNA molecules were designed to target SVCV-N and SVCV-P transcripts to inhibit SVCV replication and were tested in an epithelioma papulosum cyprini (EPC) cell line. Inhibition of gene transcription was measured by real-time quantitative reverse-transcription PCR (RT-qPCR). The efficacy of using siRNA for inhibition of viral replication was analysed by RT-qPCR measurement of a reporter gene (glycoprotein) expression and by virus endpoint titration. Inhibition of nucleoprotein and phosphoprotein gene expression by siRNA reduced SVCV replication. However, use of tandem siRNAs that target phosphoprotein and nucleoprotein worked best at reducing SVCV replication. © 2014 The Authors. Journal of Fish Diseases published by John Wiley & Sons Ltd.

Error performance analysis in downlink cellular networks with interference management

KAUST Repository

Afify, Laila H.

2015-05-01

Modeling aggregate network interference in cellular networks has recently gained immense attention both in academia and industry. While stochastic geometry based models have succeeded to account for the cellular network geometry, they mostly abstract many important wireless communication system aspects (e.g., modulation techniques, signal recovery techniques). Recently, a novel stochastic geometry model, based on the Equivalent-in-Distribution (EiD) approach, succeeded to capture the aforementioned communication system aspects and extend the analysis to averaged error performance, however, on the expense of increasing the modeling complexity. Inspired by the EiD approach, the analysis developed in [1] takes into consideration the key system parameters, while providing a simple tractable analysis. In this paper, we extend this framework to study the effect of different interference management techniques in downlink cellular network. The accuracy of the proposed analysis is verified via Monte Carlo simulations.

Hyper-modulation of brain networks by the amygdala among women with Borderline Personality Disorder: Network signatures of affective interference during cognitive processing.

Science.gov (United States)

Soloff, Paul H; Abraham, Kristy; Ramaseshan, Karthik; Burgess, Ashley; Diwadkar, Vaibhav A

2017-05-01

Emotion dysregulation is a core characteristic of patients with Borderline Personality Disorder (BPD), and is often attributed to an imbalance in fronto-limbic network function. Hyperarousal of amygdala, especially in response to negative affective stimuli, results in affective interference with cognitive processing of executive functions. Clinical consequences include the impulsive-aggression, suicidal and self-injurious behaviors which characterize BPD. Dysfunctional interactions between amygdala and its network targets have not been well characterized during cognitive task performance. Using psychophysiological interaction analysis (PPI), we mapped network profiles of amygdala interaction with key regulatory regions during a Go No-Go task, modified to use negative, positive and neutral Ekman faces as targets. Fifty-six female subjects, 31 BPD and 25 healthy controls (HC), completed the affectively valenced Go No-Go task during fMRI scanning. In the negative affective condition, the amygdala exerted greater modulation of its targets in BPD compared to HC subjects in Rt. OFC, Rt. dACC, Rt. Parietal cortex, Rt. Basal Ganglia, and Rt. dlPFC. Across the spectrum of affective contrasts, hypermodulation in BPD subjects observed the following ordering: Negative > Neutral > Positive contrast. The amygdala seed exerted modulatory effects on specific target regions important in processing response inhibition and motor impulsiveness. The vulnerability of BPD subjects to affective interference with impulse control may be due to specific network dysfunction related to amygdala hyper-arousal and its effects on prefrontal regulatory regions such as the OFC and dACC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prelife catalysts and replicators

OpenAIRE

Ohtsuki, Hisashi; Nowak, Martin A.

2009-01-01

Life is based on replication and evolution. But replication cannot be taken for granted. We must ask what there was prior to replication and evolution. How does evolution begin? We have proposed prelife as a generative system that produces information and diversity in the absence of replication. We model prelife as a binary soup of active monomers that form random polymers. ‘Prevolutionary’ dynamics can have mutation and selection prior to replication. Some sequences might have catalytic acti...

Iterative Soft Decision Interference Cancellation for DS-CDMA Employing the Distribution of Interference

Directory of Open Access Journals (Sweden)

Gerstacker WolfgangH

2010-01-01

Full Text Available A well-known receiver strategy for direct-sequence code-division multiple-access (DS-CDMA transmission is iterative soft decision interference cancellation. For calculation of soft estimates used for cancellation, the distribution of residual interference is commonly assumed to be Gaussian. In this paper, we analyze matched filter-based iterative soft decision interference cancellation (MF ISDIC when utilizing an approximation of the actual probability density function (pdf of residual interference. In addition, a hybrid scheme is proposed, which reduces computational complexity by considering the strongest residual interferers according to their pdf while the Gaussian assumption is applied to the weak residual interferers. It turns out that the bit error ratio decreases already noticeably when only a small number of residual interferers is regarded according to their pdf. For the considered DS-CDMA transmission the bit error ratio decreases by 80% for high signal-to-noise ratios when modeling all residual interferers but the strongest three to be Gaussian distributed.

Data from Investigating Variation in Replicability: A “Many Labs” Replication Project

Directory of Open Access Journals (Sweden)

Richard A. Klein

2014-04-01

Full Text Available This dataset is from the Many Labs Replication Project in which 13 effects were replicated across 36 samples and over 6,000 participants. Data from the replications are included, along with demographic variables about the participants and contextual information about the environment in which the replication was conducted. Data were collected in-lab and online through a standardized procedure administered via an online link. The dataset is stored on the Open Science Framework website. These data could be used to further investigate the results of the included 13 effects or to study replication and generalizability more broadly.

Mitigation of MIMO Co-Channel Interference using robust interference cancellation receiver

DEFF Research Database (Denmark)

Rahman, Muhammad Imadur; De Carvalho, Elisabeth; Prasad, Ramjee

2007-01-01

(STBC) link may become equivalent to an interfering Spatial Multiplexing (SM) link. Using this knowledge and understanding, we propose an interference cancellation receiver robust to different types of MIMO interferers at cell edge for the Downlink (DL) of cellular systems. The receiver systematically...... performs a multiple symbol processing: this is the appropriate processing when the signal of interest or the signal of interferer is correlated across symbols, which is the case for STBC transmission. We evaluated different link combinations in terms of Signal to Interference and Noise Ratio (SINR......) statistics and Bit Error Rate (BER) performance in cellular Orthogonal Frequency Division Multiple Access (OFDMA) systems. We have found that the proposed multiple-symbol linear interference cancellation receiver performs satisfactorily when any kind of single 'logical' stream MIMO scheme is present...

Experimental occlusal interferences. Part IV. Mandibular rotations induced by a pliable interference.

Science.gov (United States)

Christensen, L V; Rassouli, N M

1995-11-01

In 12 subjects, a pliable, yet unbreakable, intercuspal interference (aluminum shim onlay splint; uniform height of 0.25 mm) was placed between either the right or left maxillary and mandibular second premolars and first molars. During brief and forceful biting (dynamic chewing stroke of about 20 kg force) the interference emulated a semisoft food bolus, and at the end of biting (subsequent static clenching stroke of about 20 kg force) it emulated a rigid metal interference. During dynamic/static biting, rotational electrognathography measured maximum frontal and horizontal plane torque of the right and left mandibular condyles. Eleven subjects (92%) showed frontal plane upward rotation (mean of 1.0 degree) of the condyle contralateral to the interference, and one subject (8%) showed frontal plane upward rotation (0.4 degree) of the condyle ipsilateral to the interference. Two subjects (17%) showed no horizontal plane rotation; seven subjects (58%) showed backward rotation (mean of 0.4 degree) of the condyle contralateral to the interference; and three subjects (25%) showed backward rotation (mean of 0.3 degree) of the condyle ipsilateral to the interference. It is suggested that, in the presence of an occlusal interference, mastication may have both short- and long-term detrimental effects.

Periodically modulated dark states

Science.gov (United States)

Han, Yingying; Zhang, Jun; Zhang, Wenxian

2018-04-01

Phenomena of electromagnetically induced transparency (PEIT) may be interpreted by the Autler-Townes Splitting (ATS), where the coupled states are split by the coupling laser field, or by the quantum destructive interference (QDI), where the atomic phases caused by the coupling laser and the probe laser field cancel. We propose modulated experiments to explore the PEIT in an alternative way by periodically modulating the coupling and the probe fields in a Λ-type three-level system initially in a dark state. Our analytical and numerical results rule out the ATS interpretation and show that the QDI interpretation is more appropriate for the modulated experiments. Interestingly, dark state persists in the double-modulation situation where control and probe fields never occur simultaneously, which is significant difference from the traditional dark state condition. The proposed experiments are readily implemented in atomic gases, artificial atoms in superconducting quantum devices, or three-level meta-atoms in meta-materials.

Prefrontal inhibition of threat processing protects working memory from interference.

Directory of Open Access Journals (Sweden)

Robert James Clarke

2013-05-01

Full Text Available Bottom-up processes can interrupt ongoing cognitive processing in order to adaptively respond to emotional stimuli of high potential significance, such as those that threaten wellbeing. However it is vital that this interference can be modulated in certain contexts to focus on current tasks. Deficits in the ability to maintain the appropriate balance between cognitive and emotional demands can severely impact on day-to-day activities. This fMRI study examined this interaction between threat processing and cognition; 18 adult participants performed a visuospatial working memory (WM task with two load conditions, in the presence and absence of anxiety induction by threat of electric shock. Threat of shock interfered with performance in the low cognitive load condition; however interference was eradicated under high load, consistent with engagement of emotion regulation mechanisms. Under low load the amygdala showed significant activation to threat of shock that was modulated by high cognitive load. A directed top-down control contrast identified two regions associated with top-down control; ventrolateral PFC and dorsal ACC. Dynamic causal modelling provided further evidence that under high cognitive load, top-down inhibition is exerted on the amygdala and its outputs to prefrontal regions. Additionally, we hypothesised that individual differences in a separate, non-emotional top-down control task would predict the recruitment of dorsal ACC and ventrolateral PFC during top-down control of threat. Consistent with this, performance on a separate dichotic listening task predicted dorsal ACC and ventrolateral PFC activation during high WM load under threat of shock, though activation in these regions did not directly correlate with WM performance. Together, the findings suggest that under high cognitive load and threat, top-down control is exerted by dACC and vlPFC to inhibit threat processing, thus enabling WM performance without threat

Mcm2 phosphorylation and the response to replicative stress

Directory of Open Access Journals (Sweden)

Stead Brent E

2012-05-01

of Mcm2 in the response to replicative stress, including some forms of DNA damage. We suggest that phosphorylation of Mcm2 modulates Mcm2-7 activity resulting in the stabilization of replication forks in response to replicative stress.

Functions of Ubiquitin and SUMO in DNA Replication and Replication Stress

Science.gov (United States)

García-Rodríguez, Néstor; Wong, Ronald P.; Ulrich, Helle D.

2016-01-01

Complete and faithful duplication of its entire genetic material is one of the essential prerequisites for a proliferating cell to maintain genome stability. Yet, during replication DNA is particularly vulnerable to insults. On the one hand, lesions in replicating DNA frequently cause a stalling of the replication machinery, as most DNA polymerases cannot cope with defective templates. This situation is aggravated by the fact that strand separation in preparation for DNA synthesis prevents common repair mechanisms relying on strand complementarity, such as base and nucleotide excision repair, from working properly. On the other hand, the replication process itself subjects the DNA to a series of hazardous transformations, ranging from the exposure of single-stranded DNA to topological contortions and the generation of nicks and fragments, which all bear the risk of inducing genomic instability. Dealing with these problems requires rapid and flexible responses, for which posttranslational protein modifications that act independently of protein synthesis are particularly well suited. Hence, it is not surprising that members of the ubiquitin family, particularly ubiquitin itself and SUMO, feature prominently in controlling many of the defensive and restorative measures involved in the protection of DNA during replication. In this review we will discuss the contributions of ubiquitin and SUMO to genome maintenance specifically as they relate to DNA replication. We will consider cases where the modifiers act during regular, i.e., unperturbed stages of replication, such as initiation, fork progression, and termination, but also give an account of their functions in dealing with lesions, replication stalling and fork collapse. PMID:27242895

Rif1 Binding and Control of Chromosome-Internal DNA Replication Origins Is Limited by Telomere Sequestration.

Science.gov (United States)

Hafner, Lukas; Lezaja, Aleksandra; Zhang, Xu; Lemmens, Laure; Shyian, Maksym; Albert, Benjamin; Follonier, Cindy; Nunes, Jose Manuel; Lopes, Massimo; Shore, David; Mattarocci, Stefano

2018-04-24

The Saccharomyces cerevisiae telomere-binding protein Rif1 plays an evolutionarily conserved role in control of DNA replication timing by promoting PP1-dependent dephosphorylation of replication initiation factors. However, ScRif1 binding outside of telomeres has never been detected, and it has thus been unclear whether Rif1 acts directly on the replication origins that it controls. Here, we show that, in unperturbed yeast cells, Rif1 primarily regulates late-replicating origins within 100 kb of a telomere. Using the chromatin endogenous cleavage ChEC-seq technique, we robustly detect Rif1 at late-replicating origins that we show are targets of its inhibitory action. Interestingly, abrogation of Rif1 telomere association by mutation of its Rap1-binding module increases Rif1 binding and origin inhibition elsewhere in the genome. Our results indicate that Rif1 inhibits replication initiation by interacting directly with origins and suggest that Rap1-dependent sequestration of Rif1 increases its effective concentration near telomeres, while limiting its action at chromosome-internal sites. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Fabrication of sub-micrometric metallic hollow-core structures by laser interference lithography

Energy Technology Data Exchange (ETDEWEB)

Perez, Noemi; Tavera, Txaber [CEIT and Tecnun (University of Navarra) Manuel de Lardizabal 15, 20018 San Sebastian (Spain); Rodriguez, Ainara [CIC Microgune, Paseo Mikeletegi 48, 20009 San Sebastian (Spain); Ellman, Miguel; Ayerdi, Isabel; Olaizola, Santiago M. [CEIT and Tecnun (University of Navarra) Manuel de Lardizabal 15, 20018 San Sebastian (Spain)

2012-09-15

Highlights: Black-Right-Pointing-Pointer Arrays of hollow-core sub-micrometric structures are fabricated. Black-Right-Pointing-Pointer Laser interference lithography is used for the pattering of the resist sacrificial layer. Black-Right-Pointing-Pointer The removal of the sacrificial layer gives rise to metallic channels with a maximum crosssectional area of 0.1 {mu}m{sup 2}. Black-Right-Pointing-Pointer These structures can be used in nanofluidics. - Abstract: This work presents the fabrication of hollow-core metallic structures with a complete laser interference lithography (LIL) process. A negative photoresist is used as sacrificial layer. It is exposed to the pattern resulting from the interference of two laser beams, which produces a structure of photoresist lines with a period of 600 nm. After development of the resist, platinum is deposited on the samples by DC sputtering and the resist is removed with acetone. The resulting metallic structures consist in a continuous platinum film that replicates the photoresist relief with a hollow core. The cross section of the channels is up to 0.1 {mu}m{sup 2}. The fabricated samples are characterized by FESEM and FIB. This last tool helps to provide a clear picture of the shape and size of the channels. Conveniently dimensioned, this array of metallic submicrometric channels can be used in microfluidic or IC cooling applications.

Complete replication of hepatitis B virus and hepatitis C virus in a newly developed hepatoma cell line.

Science.gov (United States)

Yang, Darong; Zuo, Chaohui; Wang, Xiaohong; Meng, Xianghe; Xue, Binbin; Liu, Nianli; Yu, Rong; Qin, Yuwen; Gao, Yimin; Wang, Qiuping; Hu, Jun; Wang, Ling; Zhou, Zebin; Liu, Bing; Tan, Deming; Guan, Yang; Zhu, Haizhen

2014-04-01

The absence of a robust cell culture system for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection has limited the analysis of the virus lifecycle and drug discovery. We have established a hepatoma cell line, HLCZ01, the first cell line, to the authors' knowledge, supporting the entire lifecycle of both HBV and HCV. HBV surface antigen (HBsAg)-positive particles can be observed in the supernatant and the lumen of the endoplasmic reticulum of the cells via electron microscopy. Interestingly, HBV and HCV clinical isolates propagate in HLCZ01 cells. Both viruses replicate in the cells without evidence of overt interference. HBV and HCV entry are blocked by antibodies against HBsAg and human CD81, respectively, and the replication of HBV and HCV is inhibited by antivirals. HLCZ01 cells mount an innate immune response to virus infection. The cell line provides a powerful tool for exploring the mechanisms of virus entry and replication and the interaction between host and virus, facilitating the development of novel antiviral agents and vaccines.

NACSA Charter School Replication Guide: The Spectrum of Replication Options. Authorizing Matters. Replication Brief 1

Science.gov (United States)

O'Neill, Paul

2010-01-01

One of the most important and high-profile issues in public education reform today is the replication of successful public charter school programs. With more than 5,000 failing public schools in the United States, there is a tremendous need for strong alternatives for parents and students. Replicating successful charter school models is an…

Modulation of the photonic band structure topology of a honeycomb lattice in an atomic vapor

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yiqi, E-mail: zhangyiqi@mail.xjtu.edu.cn [Key Laboratory for Physical Electronics and Devices of the Ministry of Education & Shaanxi Key Lab of Information Photonic Technique, Xi’an Jiaotong University, Xi’an 710049 (China); Liu, Xing [Key Laboratory for Physical Electronics and Devices of the Ministry of Education & Shaanxi Key Lab of Information Photonic Technique, Xi’an Jiaotong University, Xi’an 710049 (China); Belić, Milivoj R., E-mail: milivoj.belic@qatar.tamu.edu [Science Program, Texas A& M University at Qatar, P.O. Box 23874 Doha (Qatar); Wu, Zhenkun [Key Laboratory for Physical Electronics and Devices of the Ministry of Education & Shaanxi Key Lab of Information Photonic Technique, Xi’an Jiaotong University, Xi’an 710049 (China); Zhang, Yanpeng, E-mail: ypzhang@mail.xjtu.edu.cn [Key Laboratory for Physical Electronics and Devices of the Ministry of Education & Shaanxi Key Lab of Information Photonic Technique, Xi’an Jiaotong University, Xi’an 710049 (China)

2015-12-15

In an atomic vapor, a honeycomb lattice can be constructed by utilizing the three-beam interference method. In the method, the interference of the three beams splits the dressed energy level periodically, forming a periodic refractive index modulation with the honeycomb profile. The energy band topology of the honeycomb lattice can be modulated by frequency detunings, thereby affecting the appearance (and disappearance) of Dirac points and cones in the momentum space. This effect can be usefully exploited for the generation and manipulation of topological insulators.

Dynamic remodeling of lipids coincides with dengue virus replication in the midgut of Aedes aegypti mosquitoes.

Directory of Open Access Journals (Sweden)

Nunya Chotiwan

2018-02-01

Full Text Available We describe the first comprehensive analysis of the midgut metabolome of Aedes aegypti, the primary mosquito vector for arboviruses such as dengue, Zika, chikungunya and yellow fever viruses. Transmission of these viruses depends on their ability to infect, replicate and disseminate from several tissues in the mosquito vector. The metabolic environments within these tissues play crucial roles in these processes. Since these viruses are enveloped, viral replication, assembly and release occur on cellular membranes primed through the manipulation of host metabolism. Interference with this virus infection-induced metabolic environment is detrimental to viral replication in human and mosquito cell culture models. Here we present the first insight into the metabolic environment induced during arbovirus replication in Aedes aegypti. Using high-resolution mass spectrometry, we have analyzed the temporal metabolic perturbations that occur following dengue virus infection of the midgut tissue. This is the primary site of infection and replication, preceding systemic viral dissemination and transmission. We identified metabolites that exhibited a dynamic-profile across early-, mid- and late-infection time points. We observed a marked increase in the lipid content. An increase in glycerophospholipids, sphingolipids and fatty acyls was coincident with the kinetics of viral replication. Elevation of glycerolipid levels suggested a diversion of resources during infection from energy storage to synthetic pathways. Elevated levels of acyl-carnitines were observed, signaling disruptions in mitochondrial function and possible diversion of energy production. A central hub in the sphingolipid pathway that influenced dihydroceramide to ceramide ratios was identified as critical for the virus life cycle. This study also resulted in the first reconstruction of the sphingolipid pathway in Aedes aegypti. Given conservation in the replication mechanisms of several

Dynamic remodeling of lipids coincides with dengue virus replication in the midgut of Aedes aegypti mosquitoes.

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Chotiwan, Nunya; Andre, Barbara G; Sanchez-Vargas, Irma; Islam, M Nurul; Grabowski, Jeffrey M; Hopf-Jannasch, Amber; Gough, Erik; Nakayasu, Ernesto; Blair, Carol D; Belisle, John T; Hill, Catherine A; Kuhn, Richard J; Perera, Rushika

2018-02-01

We describe the first comprehensive analysis of the midgut metabolome of Aedes aegypti, the primary mosquito vector for arboviruses such as dengue, Zika, chikungunya and yellow fever viruses. Transmission of these viruses depends on their ability to infect, replicate and disseminate from several tissues in the mosquito vector. The metabolic environments within these tissues play crucial roles in these processes. Since these viruses are enveloped, viral replication, assembly and release occur on cellular membranes primed through the manipulation of host metabolism. Interference with this virus infection-induced metabolic environment is detrimental to viral replication in human and mosquito cell culture models. Here we present the first insight into the metabolic environment induced during arbovirus replication in Aedes aegypti. Using high-resolution mass spectrometry, we have analyzed the temporal metabolic perturbations that occur following dengue virus infection of the midgut tissue. This is the primary site of infection and replication, preceding systemic viral dissemination and transmission. We identified metabolites that exhibited a dynamic-profile across early-, mid- and late-infection time points. We observed a marked increase in the lipid content. An increase in glycerophospholipids, sphingolipids and fatty acyls was coincident with the kinetics of viral replication. Elevation of glycerolipid levels suggested a diversion of resources during infection from energy storage to synthetic pathways. Elevated levels of acyl-carnitines were observed, signaling disruptions in mitochondrial function and possible diversion of energy production. A central hub in the sphingolipid pathway that influenced dihydroceramide to ceramide ratios was identified as critical for the virus life cycle. This study also resulted in the first reconstruction of the sphingolipid pathway in Aedes aegypti. Given conservation in the replication mechanisms of several flaviviruses transmitted

Polarization-induced interference within electromagnetically induced transparency for atoms of double-V linkage

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Sun, Yuan; Liu, Chang; Chen, Ping-Xing; Liu, Liang

2018-02-01

People have been paying attention to the role of atoms' complex internal level structures in the research of electromagnetically induced transparency (EIT) for a long time, where the various degenerate Zeeman levels usually generate complex linkage patterns for the atomic transitions. It turns out, with special choices of the atomic states and the atomic transitions' linkage structure, clear signatures of quantum interference induced by the probe and coupling light's polarizations can emerge from a typical EIT phenomena. We propose to study a four-state system with double-V linkage pattern for the transitions and analyze the polarization-induced interference under the EIT condition. We show that such interference arises naturally under mild conditions on the optical field and atom manipulation techniques. Moreover, we construct a variation form of double-M linkage pattern where the polarization-induced interference enables polarization-dependent cross modulation between incident weak lights that can be effective even at the few-photon level. The theme is to gain more insight into the essential question: how can we build a nontrivial optical medium where incident lights experience polarization-dependent nonlinear optical interactions, valid for a wide range of incidence intensities down to the few-photon level?

The Role of RNA Interference (RNAi in Arbovirus-Vector Interactions

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Carol D. Blair

2015-02-01

Full Text Available RNA interference (RNAi was shown over 18 years ago to be a mechanism by which arbovirus replication and transmission could be controlled in arthropod vectors. During the intervening period, research on RNAi has defined many of the components and mechanisms of this antiviral pathway in arthropods, yet a number of unexplored questions remain. RNAi refers to RNA-mediated regulation of gene expression. Originally, the term described silencing of endogenous genes by introduction of exogenous double-stranded (dsRNA with the same sequence as the gene to be silenced. Further research has shown that RNAi comprises three gene regulation pathways that are mediated by small RNAs: the small interfering (siRNA, micro (miRNA, and Piwi-interacting (piRNA pathways. The exogenous (exo-siRNA pathway is now recognized as a major antiviral innate immune response of arthropods. More recent studies suggest that the piRNA and miRNA pathways might also have important roles in arbovirus-vector interactions. This review will focus on current knowledge of the role of the exo-siRNA pathway as an arthropod vector antiviral response and on emerging research into vector piRNA and miRNA pathway modulation of arbovirus-vector interactions. Although it is assumed that arboviruses must evade the vector’s antiviral RNAi response in order to maintain their natural transmission cycles, the strategies by which this is accomplished are not well defined. RNAi is also an important tool for arthropod gene knock-down in functional genomics studies and in development of arbovirus-resistant mosquito populations. Possible arbovirus strategies for evasion of RNAi and applications of RNAi in functional genomics analysis and arbovirus transmission control will also be reviewed.

DNA Replication in Engineered Escherichia coli Genomes with Extra Replication Origins.

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Milbredt, Sarah; Farmani, Neda; Sobetzko, Patrick; Waldminghaus, Torsten

2016-10-21

The standard outline of bacterial genomes is a single circular chromosome with a single replication origin. From the bioengineering perspective, it appears attractive to extend this basic setup. Bacteria with split chromosomes or multiple replication origins have been successfully constructed in the last few years. The characteristics of these engineered strains will largely depend on the respective DNA replication patterns. However, the DNA replication has not been investigated systematically in engineered bacteria with multiple origins or split replicons. Here we fill this gap by studying a set of strains consisting of (i) E. coli strains with an extra copy of the native replication origin (oriC), (ii) E. coli strains with an extra copy of the replication origin from the secondary chromosome of Vibrio cholerae (oriII), and (iii) a strain in which the E. coli chromosome is split into two linear replicons. A combination of flow cytometry, microarray-based comparative genomic hybridization (CGH), and modeling revealed silencing of extra oriC copies and differential timing of ectopic oriII copies compared to the native oriC. The results were used to derive construction rules for future multiorigin and multireplicon projects.

Multiple DNA binding proteins contribute to timing of chromosome replication in E. coli

DEFF Research Database (Denmark)

Riber, Leise; Frimodt-Møller, Jakob; Charbon, Godefroid

2016-01-01

Chromosome replication in Escherichia coli is initiated from a single origin, oriC. Initiation involves a number of DNA binding proteins, but only DnaA is essential and specific for the initiation process. DnaA is an AAA+ protein that binds both ATP and ADP with similar high affinities. Dna...... replication is initiated, or the time window in which all origins present in a single cell are initiated, i.e. initiation synchrony, or both. Overall, these DNA binding proteins modulate the initiation frequency from oriC by: (i) binding directly to oriC to affect DnaA binding, (ii) altering the DNA topology...... in or around oriC, (iii) altering the nucleotide bound status of DnaA by interacting with non-coding chromosomal sequences, distant from oriC, that are important for DnaA activity. Thus, although DnaA is the key protein for initiation of replication, other DNA-binding proteins act not only on ori...

Hydroxyurea-Induced Replication Stress

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Kenza Lahkim Bennani-Belhaj

2010-01-01

Full Text Available Bloom's syndrome (BS displays one of the strongest known correlations between chromosomal instability and a high risk of cancer at an early age. BS cells combine a reduced average fork velocity with constitutive endogenous replication stress. However, the response of BS cells to replication stress induced by hydroxyurea (HU, which strongly slows the progression of replication forks, remains unclear due to publication of conflicting results. Using two different cellular models of BS, we showed that BLM deficiency is not associated with sensitivity to HU, in terms of clonogenic survival, DSB generation, and SCE induction. We suggest that surviving BLM-deficient cells are selected on the basis of their ability to deal with an endogenous replication stress induced by replication fork slowing, resulting in insensitivity to HU-induced replication stress.

Electro-optical time gating based on Mach-Zehnder modulator for multiple access interference elimination in optical code-division multiple access networks

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Chen, Yinfang; Wang, Rong; Fang, Tao; Pu, Tao; Xiang, Peng; Zheng, Jilin; Zhu, Huatao

2014-05-01

An electro-optical time gating technique, which is based on an electrical return-to-zero (RZ) pulse driven Mach-Zehnder modulator (MZM) for eliminating multiple access interference (MAI) in optical code-division multiple access (OCDMA) networks is proposed. This technique is successfully simulated in an eight-user two-dimensional wavelength-hopping time-spreading system, as well as in a three-user temporal phase encoding system. Results show that in both systems the MAI noise is efficiently removed and the average received power penalty improved. Both achieve error-free transmissions at a bit rate of 2.5 Gb/s. In addition, we also individually discuss effects of parameters in two systems, such as the extinction ratio of the MZM, the duty cycle of the driven RZ pulse, and the time misalignment between the driven pulse and the decoded autocorrelation peak, on the output bit error rate performance. Our work shows that employing a common MZM as a thresholder provides another probability and an interesting cost-effective choice for a smart size, low energy, and less complex thresholding technique for integrated detection in OCDMA networks.

High-Resolution Profiling of Drosophila Replication Start Sites Reveals a DNA Shape and Chromatin Signature of Metazoan Origins

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Federico Comoglio

2015-05-01

Full Text Available At every cell cycle, faithful inheritance of metazoan genomes requires the concerted activation of thousands of DNA replication origins. However, the genetic and chromatin features defining metazoan replication start sites remain largely unknown. Here, we delineate the origin repertoire of the Drosophila genome at high resolution. We address the role of origin-proximal G-quadruplexes and suggest that they transiently stall replication forks in vivo. We dissect the chromatin configuration of replication origins and identify a rich spatial organization of chromatin features at initiation sites. DNA shape and chromatin configurations, not strict sequence motifs, mark and predict origins in higher eukaryotes. We further examine the link between transcription and origin firing and reveal that modulation of origin activity across cell types is intimately linked to cell-type-specific transcriptional programs. Our study unravels conserved origin features and provides unique insights into the relationship among DNA topology, chromatin, transcription, and replication initiation across metazoa.

[Research on Spectral Polarization Imaging System Based on Static Modulation].

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Zhao, Hai-bo; Li, Huan; Lin, Xu-ling; Wang, Zheng

2015-04-01

The main disadvantages of traditional spectral polarization imaging system are: complex structure, with moving parts, low throughput. A novel method of spectral polarization imaging system is discussed, which is based on static polarization intensity modulation combined with Savart polariscope interference imaging. The imaging system can obtain real-time information of spectral and four Stokes polarization messages. Compared with the conventional methods, the advantages of the imaging system are compactness, low mass and no moving parts, no electrical control, no slit and big throughput. The system structure and the basic theory are introduced. The experimental system is established in the laboratory. The experimental system consists of reimaging optics, polarization intensity module, interference imaging module, and CCD data collecting and processing module. The spectral range is visible and near-infrared (480-950 nm). The white board and the plane toy are imaged by using the experimental system. The ability of obtaining spectral polarization imaging information is verified. The calibration system of static polarization modulation is set up. The statistical error of polarization degree detection is less than 5%. The validity and feasibility of the basic principle is proved by the experimental result. The spectral polarization data captured by the system can be applied to object identification, object classification and remote sensing detection.

Between-Trial Forgetting Due to Interference and Time in Motor Adaptation.

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Sungshin Kim

Full Text Available Learning a motor task with temporally spaced presentations or with other tasks intermixed between presentations reduces performance during training, but can enhance retention post training. These two effects are known as the spacing and contextual interference effect, respectively. Here, we aimed at testing a unifying hypothesis of the spacing and contextual interference effects in visuomotor adaptation, according to which forgetting between trials due to either spaced presentations or interference by another task will promote between-trial forgetting, which will depress performance during acquisition, but will promote retention. We first performed an experiment with three visuomotor adaptation conditions: a short inter-trial-interval (ITI condition (SHORT-ITI; a long ITI condition (LONG-ITI; and an alternating condition with two alternated opposite tasks (ALT, with the same single-task ITI as in LONG-ITI. In the SHORT-ITI condition, there was fastest increase in performance during training and largest immediate forgetting in the retention tests. In contrast, in the ALT condition, there was slowest increase in performance during training and little immediate forgetting in the retention tests. Compared to these two conditions, in the LONG-ITI, we found intermediate increase in performance during training and intermediate immediate forgetting. To account for these results, we fitted to the data six possible adaptation models with one or two time scales, and with interference in the fast, or in the slow, or in both time scales. Model comparison confirmed that two time scales and some degree of interferences in either time scale are needed to account for our experimental results. In summary, our results suggest that retention following adaptation is modulated by the degree of between-trial forgetting, which is due to time-based decay in single adaptation task and interferences in multiple adaptation tasks.

Performance analysis for optimum transmission and comparison with maximal ratio transmission for MIMO systems with cochannel interference

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Lin Sheng-Chou

2011-01-01

Full Text Available Abstract This article presents the performance analysis of multiple-input/multiple-output (MIMO systems with quadrature amplitude modulation (QAM transmission in the presence of cochannel interference (CCI in nonfading and flat Rayleigh fading environments. The use of optimum transmission (OT and maximum ratio transmission (MRT is considered and compared. In addition to determining precise results for the performance of QAM in the presence of CCI, it is our another aim in this article to examine the validity of the Gaussian interference model in the MRT-based systems. Nyquist pulse shaping and the effects of cross-channel intersymbol interference produced by CCI due to random symbol of the interfering signals are considered in the precise interference model. The error probability for each fading channel is estimated fast and accurately using Gauss quadrature rules which can approximate the probability density function (pdf of the output residual interference. The results of this article indicate that Gaussian interference model may overestimate the effects of interference, particularly, for high-order MRT-based MIMO systems over fading channels. In addition, OT cannot always outperform MRT due to the significant noise enhancement when OT intends to cancel CCI, depending on the combination of the antennas at the transmitter and the receiver, number of interference and the statistical characteristics of the channel.

Delta-9 tetrahydrocannabinol (THC) inhibits lytic replication of gamma oncogenic herpesviruses in vitro.

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Medveczky, Maria M; Sherwood, Tracy A; Klein, Thomas W; Friedman, Herman; Medveczky, Peter G

2004-09-15

The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC), has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Epstein-Barr virus (EBV) replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS) of monkeys, murine gamma herpesvirus 68 (MHV 68), and herpes simplex type 1 (HSV-1) was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC. These studies may also provide the foundation for the development

Replicating animal mitochondrial DNA

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Emily A. McKinney

2013-01-01

Full Text Available The field of mitochondrial DNA (mtDNA replication has been experiencing incredible progress in recent years, and yet little is certain about the mechanism(s used by animal cells to replicate this plasmid-like genome. The long-standing strand-displacement model of mammalian mtDNA replication (for which single-stranded DNA intermediates are a hallmark has been intensively challenged by a new set of data, which suggests that replication proceeds via coupled leading-and lagging-strand synthesis (resembling bacterial genome replication and/or via long stretches of RNA intermediates laid on the mtDNA lagging-strand (the so called RITOLS. The set of proteins required for mtDNA replication is small and includes the catalytic and accessory subunits of DNA polymerase y, the mtDNA helicase Twinkle, the mitochondrial single-stranded DNA-binding protein, and the mitochondrial RNA polymerase (which most likely functions as the mtDNA primase. Mutations in the genes coding for the first three proteins are associated with human diseases and premature aging, justifying the research interest in the genetic, biochemical and structural properties of the mtDNA replication machinery. Here we summarize these properties and discuss the current models of mtDNA replication in animal cells.

Performance Analysis of SAC Optical PPM-CDMA System-Based Interference Rejection Technique

Science.gov (United States)

Alsowaidi, N.; Eltaif, Tawfig; Mokhtar, M. R.

2016-03-01

In this paper, we aim to theoretically analyse optical code division multiple access (OCDMA) system that based on successive interference cancellation (SIC) using pulse position modulation (PPM), considering the interference between the users, imperfection cancellation occurred during the cancellation process and receiver noises. Spectral amplitude coding (SAC) scheme is used to suppress the overlapping between the users and reduce the receiver noises effect. The theoretical analysis of the multiple access interference (MAI)-limited performance of this approach indicates the influence of the size of M-ary PPM on OCDMA system. The OCDMA system performance improves with increasing M-ary PPM. Therefore, it was found that the SIC/SAC-OCDMA system using PPM technique along with modified prime (MPR) codes used as signature sequence code offers significant improvement over the one without cancellation and it can support up to 103 users at the benchmarking value of bit error rate (BER) = 10-9 with prime number p = 11 while the system without cancellation scheme can support only up to 52 users.

A Scalable Permutation Approach Reveals Replication and Preservation Patterns of Network Modules in Large Datasets.

Science.gov (United States)

Ritchie, Scott C; Watts, Stephen; Fearnley, Liam G; Holt, Kathryn E; Abraham, Gad; Inouye, Michael

2016-07-01

Network modules-topologically distinct groups of edges and nodes-that are preserved across datasets can reveal common features of organisms, tissues, cell types, and molecules. Many statistics to identify such modules have been developed, but testing their significance requires heuristics. Here, we demonstrate that current methods for assessing module preservation are systematically biased and produce skewed p values. We introduce NetRep, a rapid and computationally efficient method that uses a permutation approach to score module preservation without assuming data are normally distributed. NetRep produces unbiased p values and can distinguish between true and false positives during multiple hypothesis testing. We use NetRep to quantify preservation of gene coexpression modules across murine brain, liver, adipose, and muscle tissues. Complex patterns of multi-tissue preservation were revealed, including a liver-derived housekeeping module that displayed adipose- and muscle-specific association with body weight. Finally, we demonstrate the broader applicability of NetRep by quantifying preservation of bacterial networks in gut microbiota between men and women. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

The role of task interference and exposure duration in judging noise annoyance

Science.gov (United States)

Zimmer, Karin; Ghani, Jody; Ellermeier, Wolfgang

2008-04-01

To determine whether the amount of performance disruption by a noise has an effect on the annoyance that noise evokes, a laboratory situation was created in which the participants rated a number of sounds before, after, and while performing a cognitively demanding memory task. The task consisted of memorizing, and later reproducing, a visually presented sequence of digits while being exposed to irrelevant sound chosen to produce different degrees of disruption. In two experiments, participants assessed these background sounds (frequency-modulated tones, broadband noise and speech) on a rating scale consisting of thirteen categories ranging from 'not annoying at all' to 'extremely annoying.' The judgments were collected immediately before, after, and concomitant to, the memory task. The results of the first experiment (N=24) showed that the annoyance assessments were indeed altered by the experience of disruption, most strongly during, and to a lesser extent after task completion, whereas ratings of the non-disruptive sounds remained largely unaffected. In the second experiment (N=25), participants were exposed to the same sounds, but for longer intervals at a time: 10 min as opposed to 14 s in the first experiment. The longer exposure resulted in increased annoyance in all noise conditions, but did not alter the differential effect of disruption on annoyance, which was replicated. The results of these laboratory experiments support the notion that annoyance cannot be conceived of as a purely perceptual sound property; rather, it is influenced by the degree of interference with the task at hand.

Modeling inhomogeneous DNA replication kinetics.

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Michel G Gauthier

Full Text Available In eukaryotic organisms, DNA replication is initiated at a series of chromosomal locations called origins, where replication forks are assembled proceeding bidirectionally to replicate the genome. The distribution and firing rate of these origins, in conjunction with the velocity at which forks progress, dictate the program of the replication process. Previous attempts at modeling DNA replication in eukaryotes have focused on cases where the firing rate and the velocity of replication forks are homogeneous, or uniform, across the genome. However, it is now known that there are large variations in origin activity along the genome and variations in fork velocities can also take place. Here, we generalize previous approaches to modeling replication, to allow for arbitrary spatial variation of initiation rates and fork velocities. We derive rate equations for left- and right-moving forks and for replication probability over time that can be solved numerically to obtain the mean-field replication program. This method accurately reproduces the results of DNA replication simulation. We also successfully adapted our approach to the inverse problem of fitting measurements of DNA replication performed on single DNA molecules. Since such measurements are performed on specified portion of the genome, the examined DNA molecules may be replicated by forks that originate either within the studied molecule or outside of it. This problem was solved by using an effective flux of incoming replication forks at the model boundaries to represent the origin activity outside the studied region. Using this approach, we show that reliable inferences can be made about the replication of specific portions of the genome even if the amount of data that can be obtained from single-molecule experiments is generally limited.

Mechanisms of DNA replication termination.

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Dewar, James M; Walter, Johannes C

2017-08-01

Genome duplication is carried out by pairs of replication forks that assemble at origins of replication and then move in opposite directions. DNA replication ends when converging replication forks meet. During this process, which is known as replication termination, DNA synthesis is completed, the replication machinery is disassembled and daughter molecules are resolved. In this Review, we outline the steps that are likely to be common to replication termination in most organisms, namely, fork convergence, synthesis completion, replisome disassembly and decatenation. We briefly review the mechanism of termination in the bacterium Escherichia coli and in simian virus 40 (SV40) and also focus on recent advances in eukaryotic replication termination. In particular, we discuss the recently discovered E3 ubiquitin ligases that control replisome disassembly in yeast and higher eukaryotes, and how their activity is regulated to avoid genome instability.

Affective Modulation of the Startle Eyeblink and Postauricular Reflexes in Autism Spectrum Disorder

Science.gov (United States)

Dichter, Gabriel S.; Benning, Stephen D.; Holtzclaw, Tia N.; Bodfish, James W.

2010-01-01

Eyeblink and postauricular reflexes to standardized affective images were examined in individuals without (n = 37) and with (n = 20) autism spectrum disorders (ASDs). Affective reflex modulation in control participants replicated previous findings. The ASD group, however, showed anomalous reflex modulation patterns, despite similar self-report…

Patient examinations using electrical impedance tomography—sources of interference in the intensive care unit

International Nuclear Information System (INIS)

Frerichs, Inéz; Pulletz, Sven; Elke, Gunnar; Gawelczyk, Barbara; Frerichs, Alexander; Weiler, Norbert

2011-01-01

Electrical impedance tomography (EIT) is expected to become a valuable tool for monitoring mechanically ventilated patients due to its ability to continuously assess regional lung ventilation and aeration. Several sources of interference with EIT examinations exist in intensive care units (ICU). Our objectives are to demonstrate how some medical nursing and monitoring devices interfere with EIT measurements and modify the EIT scans and waveforms, which approaches can be applied to minimize these effects and how possible misinterpretation can be avoided. We present four cases of EIT examinations of adult ICU patients. Two of the patients were subjected to pulsation therapy using a pulsating air suspension mattress while being ventilated by high-frequency oscillatory or conventional pressure-controlled ventilation, respectively. The EIT signal modulation synchronous with the occurrence of the pulsating wave was 2.3 times larger than the periodic modulation synchronous with heart rate and high-frequency oscillations. During conventional ventilation, the pulsating mattress induced an EIT signal fluctuation with a magnitude corresponding to about 20% of the patient's tidal volume. In the third patient, interference with EIT examination was caused by continuous cardiac output monitoring. The last patient's examination was disturbed by impedance pneumography when excitation currents of similar frequency to EIT were used. In all subjects, the generation of functional EIT scans was compromised and interpretation of regional ventilation impossible. Discontinuation of pulsation therapy and of continuous cardiac output and impedance respiration monitoring immediately improved the EIT signal and scan quality. Offline processing of the disturbed data using frequency filtering enabled partial retrieval of relevant information. We conclude that thoracic EIT examinations in the ICU require cautious interpretation because of possible mechanical and electromagnetic

Elementary Statistical Models for Vector Collision-Sequence Interference Effects with Poisson-Distributed Collision Times

International Nuclear Information System (INIS)

Lewis, J.C.

2011-01-01

In a recent paper (Lewis, 2008) a class of models suitable for application to collision-sequence interference was introduced. In these models velocities are assumed to be completely randomized in each collision. The distribution of velocities was assumed to be Gaussian. The integrated induced dipole moment μk, for vector interference, or the scalar modulation μk, for scalar interference, was assumed to be a function of the impulse (integrated force) fk, or its magnitude fk, experienced by the molecule in a collision. For most of (Lewis, 2008) it was assumed that μk fk and μk fk, but it proved to be possible to extend the models, so that the magnitude of the induced dipole moment is equal to an arbitrary power or sum of powers of the intermolecular force. This allows estimates of the in filling of the interference dip by the dis proportionality of the induced dipole moment and force. One particular such model, using data from (Herman and Lewis, 2006), leads to the most realistic estimate for the in filling of the vector interference dip yet obtained. In (Lewis, 2008) the drastic assumption was made that collision times occurred at equal intervals. In the present paper that assumption is removed: the collision times are taken to form a Poisson process. This is much more realistic than the equal-intervals assumption. The interference dip is found to be a Lorentzian in this model

Rolling replication of UV-irradiated duplex DNA in the phi X174 replicative-form----single-strand replication system in vitro

International Nuclear Information System (INIS)

Shavitt, O.; Livneh, Z.

1989-01-01

Cloning of the phi X174 viral origin of replication into phage M13mp8 produced an M13-phi X174 chimera, the DNA of which directed efficient replicative-form----single-strand rolling replication in vitro. This replication assay was performed with purified phi X174-encoded gene A protein, Escherichia coli rep helicase, single-stranded DNA-binding protein, and DNA polymerase III holoenzyme. The nicking of replicative-form I (RFI) DNA by gene A protein was essentially unaffected by the presence of UV lesions in the DNA. However, unwinding of UV-irradiated DNA by the rep helicase was inhibited twofold as compared with unwinding of the unirradiated substrate. UV irradiation of the substrate DNA caused a strong inhibition in its ability to direct DNA synthesis. However, even DNA preparations that contained as many as 10 photodimers per molecule still supported the synthesis of progeny full-length single-stranded DNA. The appearance of full-length radiolabeled products implied at least two full rounds of replication, since the first round released the unlabeled plus viral strand of the duplex DNA. Pretreatment of the UV-irradiated DNA substrate with purified pyrimidine dimer endonuclease from Micrococcus luteus, which converted photodimer-containing supercoiled RFI DNA into relaxed, nicked RFII DNA and thus prevented its replication, reduced DNA synthesis by 70%. Analysis of radiolabeled replication products by agarose gel electrophoresis followed by autoradiography revealed that this decrease was due to a reduction in the synthesis of progeny full-length single-stranded DNA. This implies that 70 to 80% of the full-length DNA products produced in this system were synthesized on molecules that carried photodimers

Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks

DEFF Research Database (Denmark)

Sotiriou, Sotirios K; Kamileri, Irene; Lugli, Natalia

2016-01-01

Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose...... RAD52 facilitates repair of collapsed DNA replication forks in cancer cells....

REPLICATION TOOL AND METHOD OF PROVIDING A REPLICATION TOOL

DEFF Research Database (Denmark)

2016-01-01

The invention relates to a replication tool (1, 1a, 1b) for producing a part (4) with a microscale textured replica surface (5a, 5b, 5c, 5d). The replication tool (1, 1a, 1b) comprises a tool surface (2a, 2b) defining a general shape of the item. The tool surface (2a, 2b) comprises a microscale...... energy directors on flange portions thereof uses the replication tool (1, 1a, 1b) to form an item (4) with a general shape as defined by the tool surface (2a, 2b). The formed item (4) comprises a microscale textured replica surface (5a, 5b, 5c, 5d) with a lateral arrangement of polydisperse microscale...

Recruitment of a SAP18-HDAC1 complex into HIV-1 virions and its requirement for viral replication.

Directory of Open Access Journals (Sweden)

Masha Sorin

2009-06-01

Full Text Available HIV-1 integrase (IN is a virally encoded protein required for integration of viral cDNA into host chromosomes. INI1/hSNF5 is a component of the SWI/SNF complex that interacts with HIV-1 IN, is selectively incorporated into HIV-1 (but not other retroviral virions, and modulates multiple steps, including particle production and infectivity. To gain further insight into the role of INI1 in HIV-1 replication, we screened for INI1-interacting proteins using the yeast two-hybrid system. We found that SAP18 (Sin3a associated protein 18 kD, a component of the Sin3a-HDAC1 complex, directly binds to INI1 in yeast, in vitro and in vivo. Interestingly, we found that IN also binds to SAP18 in vitro and in vivo. SAP18 and components of a Sin3A-HDAC1 complex were specifically incorporated into HIV-1 (but not SIV and HTLV-1 virions in an HIV-1 IN-dependent manner. Using a fluorescence-based assay, we found that HIV-1 (but not SIV virion preparations harbour significant deacetylase activity, indicating the specific recruitment of catalytically active HDAC into the virions. To determine the requirement of virion-associated HDAC1 to HIV-1 replication, an inactive, transdominant negative mutant of HDAC1 (HDAC1(H141A was utilized. Incorporation of HDAC1(H141A decreased the virion-associated histone deacetylase activity. Furthermore, incorporation of HDAC1(H141A decreased the infectivity of HIV-1 (but not SIV virions. The block in infectivity due to virion-associated HDAC1(H141A occurred specifically at the early reverse transcription stage, while entry of the virions was unaffected. RNA-interference mediated knock-down of HDAC1 in producer cells resulted in decreased virion-associated HDAC1 activity and a reduction in infectivity of these virions. These studies indicate that HIV-1 IN and INI1/hSNF5 bind SAP18 and selectively recruit components of Sin3a-HDAC1 complex into HIV-1 virions. Furthermore, HIV-1 virion-associated HDAC1 is required for efficient early post

Inhibition of HSV-1 replication by laser diode-irradiation: possible mechanism of action.

Science.gov (United States)

Donnarumma, G; De Gregorio, V; Fusco, A; Farina, E; Baroni, A; Esposito, V; Contaldo, M; Petruzzi, M; Pannone, G; Serpico, R

2010-01-01

Herpes labialis are the most frequent clinical manifestations of HSV-1 infection. Epithelial cells are able to respond to HSV-1 presence inducing the expression of IL-6, IL-1, TNF-α and IL-8. These proinflammatory cytokines have a function in the acute-phase response mediation, chemotaxis, inflammatory cell activation and antigen-presenting cells. In the human epithelial cell models, it has been demonstrated that, after an early induction of proinflammatory host response, HSV-1 down-modulates the proinflammatory cytokine production through the accumulation of two viral proteins, ICP4 and ICP27, whose transcription is induced by tegument protein VP16. These viral proteins, through the decreasing of stabilizing the mRNAs of proinflammatory genes, delay cytokine production to an extent that allows the virus to replicate. Moreover, viral transactivating proteins, ICP-0 and VP-16 induce IL-10 expression. The conventional treatment of herpes labialis involves the topical and systemic use of antiviral drugs but it is necessary to find new therapies that can act in a selective and non-cytotoxic manner in viral infection. Laser diode therapy has been considered as a non-invasive alternative treatment to the conventional treatment of herpes labialis in pain therapy, in modulation of inflammation and in wound healing. This study aims to report a possible mechanism of action of laser diode irradiation in prevention and reduction of severity of labial manifestations of herpes labialis virus. We investigated, in an in vitro model of epithelial cells HaCat, the laser-effect on HSV-1 replication and we evaluated the modulation of expression of certain proinflammatory cytokines (TNF-α, IL-1β and IL-6), antimicrobial peptide HBD2, chemokine IL-8 and the immunosuppressive cytokine, IL-10. Our results lead us to hypothesize that LD-irradiation acts in the final stage of HSV-1 replication by limiting viral spread from cell to cell and that laser therapy acts also on the host immune

Interference Calculus A General Framework for Interference Management and Network Utility Optimization

CERN Document Server

Schubert, Martin

2012-01-01

This book develops a mathematical framework for modeling and optimizing interference-coupled multiuser systems. At the core of this framework is the concept of general interference functions, which provides a simple means of characterizing interdependencies between users. The entire analysis builds on the two core axioms scale-invariance and monotonicity. The proposed network calculus has its roots in power control theory and wireless communications. It adds theoretical tools for analyzing the typical behavior of interference-coupled networks. In this way it complements existing game-theoretic approaches. The framework should also be viewed in conjunction with optimization theory. There is a fruitful interplay between the theory of interference functions and convex optimization theory. By jointly exploiting the properties of interference functions, it is possible to design algorithms that outperform general-purpose techniques that only exploit convexity. The title “network calculus” refers to the fact tha...

Recommendations for Replication Research in Special Education: A Framework of Systematic, Conceptual Replications

Science.gov (United States)

Coyne, Michael D.; Cook, Bryan G.; Therrien, William J.

2016-01-01

Special education researchers conduct studies that can be considered replications. However, they do not often refer to them as replication studies. The purpose of this article is to consider the potential benefits of conceptualizing special education intervention research within a framework of systematic, conceptual replication. Specifically, we…

DNA replication and cancer

DEFF Research Database (Denmark)

Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard

2016-01-01

A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways...... causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy....

Late-replicating X-chromosome: replication patterns in mammalian females

Directory of Open Access Journals (Sweden)

Tunin Karen

2002-01-01

Full Text Available The GTG-banding and 5-BrdU incorporation patterns of the late-replicating X-chromosome were studied in female dogs and cattle, and compared to human female patterns. The replication patterns of the short arm of the X-chromosomes did not show any difference between human, dog and cattle females. As to the long arm, some bands showed differences among the three studied species regarding the replication kinetics pattern. These differences were observed in a restricted region of the X-chromosome, delimited by Xq11 -> q25 in humans, by Xq1 -> q8 in dogs, and by Xq12 -> q32 in cattle. In an attempt to find out if these differences in the replication kinetics could be a reflection of differences in the localization of genes in that region of the X-chromosome, we used the probe for the human androgen receptor gene (AR localized at Xq12, which is in the region where we observed differences among the three studied species. We did not, however, observe hybridization signals. Our study goes on, using other human probes for genes located in the region Xq11 -> Xq25.

A Replication by Any Other Name: A Systematic Review of Replicative Intervention Studies

Science.gov (United States)

Cook, Bryan G.; Collins, Lauren W.; Cook, Sara C.; Cook, Lysandra

2016-01-01

Replication research is essential to scientific knowledge. Reviews of replication studies often electronically search for "replicat*" as a textword, which does not identify studies that replicate previous research but do not self-identify as such. We examined whether the 83 intervention studies published in six non-categorical research…

Registered Replication Report

DEFF Research Database (Denmark)

Bouwmeester, S.; Verkoeijen, P. P.J.L.; Aczel, B.

2017-01-01

and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed...... the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned...

Optical encryption using pseudorandom complex spatial modulation.

Science.gov (United States)

Sarkadi, Tamás; Koppa, Pál

2012-12-01

In this paper we propose a new (to our knowledge) complex spatial modulation method to encode data pages applicable in double random phase encryption (DRPE) to make the system more resistant to brute-force attack. The proposed modulation method uses data page pixels with random phase and amplitude values with the condition that the intensity of the interference of light from two adjacent pixels should correspond to the encoded information. A differential phase contrast technique is applied to recover the data page at the output of the system. We show that the proposed modulation method can enhance the robustness of the DRPE technique using point spread function analysis. Key space expansion is determined by numeric model calculations.

International Expansion through Flexible Replication

DEFF Research Database (Denmark)

Jonsson, Anna; Foss, Nicolai Juul

2011-01-01

Business organizations may expand internationally by replicating a part of their value chain, such as a sales and marketing format, in other countries. However, little is known regarding how such “international replicators” build a format for replication, or how they can adjust it in order to ada......, etc.) are replicated in a uniform manner across stores, and change only very slowly (if at all) in response to learning (“flexible replication”). We conclude by discussing the factors that influence the approach to replication adopted by an international replicator.......Business organizations may expand internationally by replicating a part of their value chain, such as a sales and marketing format, in other countries. However, little is known regarding how such “international replicators” build a format for replication, or how they can adjust it in order to adapt...

Enhanced conditioned eyeblink response acquisition and proactive interference in anxiety vulnerable individuals

Directory of Open Access Journals (Sweden)

Jacqueline L Holloway

2012-11-01

Full Text Available In classical conditioning, proactive interference may arise from experience with the conditioned stimulus (CS, the unconditional stimulus (US, or both, prior to their paired presentations. Interest in the application of proactive interference has extended to clinical populations as either a risk factor for disorders or as a secondary sign. Although the current literature is dense with comparisons of stimulus pre-exposure effects in animals, such comparisons are lacking in human subjects. As such, interpretation of proactive interference over studies as well as its generalization and utility in clinical research is limited. The present study was designed to assess eyeblink response acquisition after equal numbers of CS, US, and explicitly unpaired CS and US pre-exposures, as well as to evaluate how anxiety vulnerability might modulate proactive interference. In the current study, anxiety vulnerability was assessed using the State/Trait Anxiety Inventories as well as the adult and retrospective measures of behavioural inhibition (AMBI and RMBI, respectively. Participants were exposed to 1 of 4 possible pre-exposure contingencies: 30 CS, 30 US, 30 CS and 30 US explicitly unpaired pre-exposures, or context pre-exposure, immediately prior to standard delay training. Robust proactive interference was evident in all pre-exposure groups relative to context pre-exposure, independent of anxiety classification, with CR acquisition attenuated at similar rates. In addition, trait anxious individuals were found to have enhanced overall acquisition as well as greater proactive interference relative to non-vulnerable individuals. The findings suggest that anxiety vulnerable individuals learn implicit associations faster, an effect which persists after the introduction of new stimulus contingencies. This effect is not due to enhanced sensitivity to the US. Such differences would have implications for the development of anxiety psychopathology within a learning

Enhanced conditioned eyeblink response acquisition and proactive interference in anxiety vulnerable individuals.

Science.gov (United States)

Holloway, Jacqueline L; Trivedi, Payal; Myers, Catherine E; Servatius, Richard J

2012-01-01

In classical conditioning, proactive interference may arise from experience with the conditioned stimulus (CS), the unconditional stimulus (US), or both, prior to their paired presentations. Interest in the application of proactive interference has extended to clinical populations as either a risk factor for disorders or as a secondary sign. Although the current literature is dense with comparisons of stimulus pre-exposure effects in animals, such comparisons are lacking in human subjects. As such, interpretation of proactive interference over studies as well as its generalization and utility in clinical research is limited. The present study was designed to assess eyeblink response acquisition after equal numbers of CS, US, and explicitly unpaired CS and US pre-exposures, as well as to evaluate how anxiety vulnerability might modulate proactive interference. In the current study, anxiety vulnerability was assessed using the State/Trait Anxiety Inventories as well as the adult and retrospective measures of behavioral inhibition (AMBI and RMBI, respectively). Participants were exposed to 1 of 4 possible pre-exposure contingencies: 30 CS, 30 US, 30 CS, and 30 US explicitly unpaired pre-exposures, or Context pre-exposure, immediately prior to standard delay training. Robust proactive interference was evident in all pre-exposure groups relative to Context pre-exposure, independent of anxiety classification, with CR acquisition attenuated at similar rates. In addition, trait anxious individuals were found to have enhanced overall acquisition as well as greater proactive interference relative to non-vulnerable individuals. The findings suggest that anxiety vulnerable individuals learn implicit associations faster, an effect which persists after the introduction of new stimulus contingencies. This effect is not due to enhanced sensitivity to the US. Such differences would have implications for the development of anxiety psychopathology within a learning framework.

Sterol Binding by the Tombusviral Replication Proteins Is Essential for Replication in Yeast and Plants.

Science.gov (United States)

Xu, Kai; Nagy, Peter D

2017-04-01

Membranous structures derived from various organelles are important for replication of plus-stranded RNA viruses. Although the important roles of co-opted host proteins in RNA virus replication have been appreciated for a decade, the equally important functions of cellular lipids in virus replication have been gaining full attention only recently. Previous work with Tomato bushy stunt tombusvirus (TBSV) in model host yeast has revealed essential roles for phosphatidylethanolamine and sterols in viral replication. To further our understanding of the role of sterols in tombusvirus replication, in this work we showed that the TBSV p33 and p92 replication proteins could bind to sterols in vitro The sterol binding by p33 is supported by cholesterol recognition/interaction amino acid consensus (CRAC) and CARC-like sequences within the two transmembrane domains of p33. Mutagenesis of the critical Y amino acids within the CRAC and CARC sequences blocked TBSV replication in yeast and plant cells. We also showed the enrichment of sterols in the detergent-resistant membrane (DRM) fractions obtained from yeast and plant cells replicating TBSV. The DRMs could support viral RNA synthesis on both the endogenous and exogenous templates. A lipidomic approach showed the lack of enhancement of sterol levels in yeast and plant cells replicating TBSV. The data support the notion that the TBSV replication proteins are associated with sterol-rich detergent-resistant membranes in yeast and plant cells. Together, the results obtained in this study and the previously published results support the local enrichment of sterols around the viral replication proteins that is critical for TBSV replication. IMPORTANCE One intriguing aspect of viral infections is their dependence on efficient subcellular assembly platforms serving replication, virion assembly, or virus egress via budding out of infected cells. These assembly platforms might involve sterol-rich membrane microdomains, which are

The fork and the kinase: a DNA replication tale from a CHK1 perspective.

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González Besteiro, Marina A; Gottifredi, Vanesa

2015-01-01

Replication fork progression is being continuously hampered by exogenously introduced and naturally occurring DNA lesions and other physical obstacles. Checkpoint kinase 1 (Chk1) is activated at replication forks that encounter damaged DNA. Subsequently, Chk1 inhibits the initiation of new replication factories and stimulates the firing of dormant origins (those in the vicinity of stalled forks). Chk1 also avoids fork collapse into DSBs (double strand breaks) and promotes fork elongation. At the molecular level, the current model considers stalled forks as the site of Chk1 activation and the nucleoplasm as the location where Chk1 phosphorylates target proteins. This model certainly serves to explain how Chk1 modulates origin firing, but how Chk1 controls the fate of stalled forks is less clear. Interestingly, recent reports demonstrating that Chk1 phosphorylates chromatin-bound proteins and even holds kinase-independent functions might shed light on how Chk1 contributes to the elongation of damaged DNA. Indeed, such findings have unveiled a puzzling connection between Chk1 and DNA lesion bypass, which might be central to promoting fork elongation and checkpoint attenuation. In summary, Chk1 is a multifaceted and versatile signaling factor that acts at ongoing forks and replication origins to determine the extent and quality of the cellular response to replication stress. Copyright © 2014 Elsevier B.V. All rights reserved.

REM sleep rescues learning from interference

Science.gov (United States)

McDevitt, Elizabeth A.; Duggan, Katherine A.; Mednick, Sara C.

2015-01-01

Classical human memory studies investigating the acquisition of temporally-linked events have found that the memories for two events will interfere with each other and cause forgetting (i.e., interference; Wixted, 2004). Importantly, sleep helps consolidate memories and protect them from subsequent interference (Ellenbogen, Hulbert, Stickgold, Dinges, & Thompson-Schill, 2006). We asked whether sleep can also repair memories that have already been damaged by interference. Using a perceptual learning paradigm, we induced interference either before or after a consolidation period. We varied brain states during consolidation by comparing active wake, quiet wake, and naps with either non-rapid eye movement sleep (NREM), or both NREM and REM sleep. When interference occurred after consolidation, sleep and wake both produced learning. However, interference prior to consolidation impaired memory, with retroactive interference showing more disruption than proactive interference. Sleep rescued learning damaged by interference. Critically, only naps that contained REM sleep were able to rescue learning that was highly disrupted by retroactive interference. Furthermore, the magnitude of rescued learning was correlated with the amount of REM sleep. We demonstrate the first evidence of a process by which the brain can rescue and consolidate memories damaged by interference, and that this process requires REM sleep. We explain these results within a theoretical model that considers how interference during encoding interacts with consolidation processes to predict which memories are retained or lost. PMID:25498222

Large-scale replication study reveals a limit on probabilistic prediction in language comprehension.

Science.gov (United States)

Nieuwland, Mante S; Politzer-Ahles, Stephen; Heyselaar, Evelien; Segaert, Katrien; Darley, Emily; Kazanina, Nina; Von Grebmer Zu Wolfsthurn, Sarah; Bartolozzi, Federica; Kogan, Vita; Ito, Aine; Mézière, Diane; Barr, Dale J; Rousselet, Guillaume A; Ferguson, Heather J; Busch-Moreno, Simon; Fu, Xiao; Tuomainen, Jyrki; Kulakova, Eugenia; Husband, E Matthew; Donaldson, David I; Kohút, Zdenko; Rueschemeyer, Shirley-Ann; Huettig, Falk

2018-04-03

Do people routinely pre-activate the meaning and even the phonological form of upcoming words? The most acclaimed evidence for phonological prediction comes from a 2005 Nature Neuroscience publication by DeLong, Urbach and Kutas, who observed a graded modulation of electrical brain potentials (N400) to nouns and preceding articles by the probability that people use a word to continue the sentence fragment ('cloze'). In our direct replication study spanning 9 laboratories ( N =334), pre-registered replication-analyses and exploratory Bayes factor analyses successfully replicated the noun-results but, crucially, not the article-results. Pre-registered single-trial analyses also yielded a statistically significant effect for the nouns but not the articles. Exploratory Bayesian single-trial analyses showed that the article-effect may be non-zero but is likely far smaller than originally reported and too small to observe without very large sample sizes. Our results do not support the view that readers routinely pre-activate the phonological form of predictable words. © 2018, Nieuwland et al.

Mcm10 regulates DNA replication elongation by stimulating the CMG replicative helicase.

Science.gov (United States)

Lõoke, Marko; Maloney, Michael F; Bell, Stephen P

2017-02-01

Activation of the Mcm2-7 replicative DNA helicase is the committed step in eukaryotic DNA replication initiation. Although Mcm2-7 activation requires binding of the helicase-activating proteins Cdc45 and GINS (forming the CMG complex), an additional protein, Mcm10, drives initial origin DNA unwinding by an unknown mechanism. We show that Mcm10 binds a conserved motif located between the oligonucleotide/oligosaccharide fold (OB-fold) and A subdomain of Mcm2. Although buried in the interface between these domains in Mcm2-7 structures, mutations predicted to separate the domains and expose this motif restore growth to conditional-lethal MCM10 mutant cells. We found that, in addition to stimulating initial DNA unwinding, Mcm10 stabilizes Cdc45 and GINS association with Mcm2-7 and stimulates replication elongation in vivo and in vitro. Furthermore, we identified a lethal allele of MCM10 that stimulates initial DNA unwinding but is defective in replication elongation and CMG binding. Our findings expand the roles of Mcm10 during DNA replication and suggest a new model for Mcm10 function as an activator of the CMG complex throughout DNA replication. © 2017 Lõoke et al.; Published by Cold Spring Harbor Laboratory Press.

Characterization of polarization-independent phase modulation method for practical plug and play quantum cryptography

International Nuclear Information System (INIS)

Kwon, Osung; Lee, Min-Soo; Woo, Min Ki; Park, Byung Kwon; Kim, Il Young; Kim, Yong-Su; Han, Sang-Wook; Moon, Sung

2015-01-01

We characterized a polarization-independent phase modulation method, called double phase modulation, for a practical plug and play quantum key distribution (QKD) system. Following investigation of theoretical backgrounds, we applied the method to the practical QKD system and characterized the performance through comparing single phase modulation (SPM) and double phase modulation. Consequently, we obtained repeatable and accurate phase modulation confirmed by high visibility single photon interference even for input signals with arbitrary polarization. Further, the results show that only 80% of the bias voltage required in the case of single phase modulation is needed to obtain the target amount of phase modulation. (paper)

Temporary interference over the posterior parietal cortices disrupts thermoregulatory control in humans.

Directory of Open Access Journals (Sweden)

Alberto Gallace

Full Text Available The suggestion has recently been made that certain higher-order cortical areas involved in supporting multisensory representations of the body, and of the space around it, might also play a role in controlling thermoregulatory functions. Here we demonstrate that temporary interference with the function of one of these areas, the posterior parietal cortex, by repetitive transcranial magnetic stimulation, results in a decrease in limb temperature. By contrast, interference with the activity of a sensory-specific area (the primary somatosensory cortex had no effect on temperature. The results of this experiment suggest that associative multisensory brain areas might exert a top-down modulation over basic physiological control. Such a function might be part of a larger neural circuit responsible for maintaining the integrity of the body at both a homeostatic and a psychological level.

Naming and categorizing objects: task differences modulate the polarity of semantic effects in the picture-word interference paradigm.

Science.gov (United States)

Hantsch, Ansgar; Jescheniak, Jörg D; Mädebach, Andreas

2012-07-01

The picture-word interference paradigm is a prominent tool for studying lexical retrieval during speech production. When participants name the pictures, interference from semantically related distractor words has regularly been shown. By contrast, when participants categorize the pictures, facilitation from semantically related distractors has typically been found. In the extant studies, however, differences in the task instructions (naming vs. categorizing) were confounded with the response level: While responses in naming were typically located at the basic level (e.g., "dog"), responses were located at the superordinate level in categorization (e.g., "animal"). The present study avoided this confound by having participants respond at the basic level in both naming and categorization, using the same pictures, distractors, and verbal responses. Our findings confirm the polarity reversal of the semantic effects--that is, semantic interference in naming, and semantic facilitation in categorization. These findings show that the polarity reversal of the semantic effect is indeed due to the different tasks and is not an artifact of the different response levels used in previous studies. Implications for current models of language production are discussed.

Induction and characterization of a replication competent cervid endogenous gammaretrovirus (CrERV) from mule deer cells.

Science.gov (United States)

Fábryová, Helena; Hron, Tomáš; Kabíčková, Hana; Poss, Mary; Elleder, Daniel

2015-11-01

Endogenous retroviruses (ERVs) were acquired during evolution of their host organisms after infection and mendelian inheritance in the germline by their exogenous counterparts. The ERVs can spread in the host genome and in some cases they affect the host phenotype. The cervid endogenous gammaretrovirus (CrERV) is one of only a few well-defined examples of evolutionarily recent invasion of mammalian genome by retroviruses. Thousands of insertionally polymorphic CrERV integration sites have been detected in wild ranging mule deer (Odocoileus hemionus) host populations. Here, we describe for the first time induction of replication competent CrERV by cocultivation of deer and human cells. We characterize the physical properties and tropism of the induced virus. The genomic sequence of the induced virus is phylogenetically related to the evolutionarily young endogenous CrERVs described so far. We also describe the level of replication block of CrERV on deer cells and its capacity to establish superinfection interference. Copyright © 2015 Elsevier Inc. All rights reserved.

PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication.

Science.gov (United States)

Hou, Jiun-Nan; Chen, Tien-Huang; Chiang, Yi-Hsuan; Peng, Jing-Yun; Yang, Tsong-Han; Cheng, Chih-Chieh; Sofiyatun, Eny; Chiu, Cheng-Hsun; Chiang-Ni, Chuan; Chen, Wei-June

2017-09-20

pathway modulates dynamic translation of proteins and helps mosquito cells survive continuous replication of the DENV2. It was ecologically important for virus amplification in mosquitoes and transmission to humans.

Delta-9 tetrahydrocannabinol (THC inhibits lytic replication of gamma oncogenic herpesviruses in vitro

Directory of Open Access Journals (Sweden)

Friedman Herman

2004-09-01

Full Text Available Abstract Background The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC, has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. Methods Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV and Epstein-Barr virus (EBV replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS of monkeys, murine gamma herpesvirus 68 (MHV 68, and herpes simplex type 1 (HSV-1 was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. Results Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. Conclusions THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC

Interference in motor learning - is motor interference sensory?

DEFF Research Database (Denmark)

Jensen, Jesper Lundbye; Petersen, Tue Hvass; Rothwell, John C

mechanisms determine whether or not interference occurs. We hypothesised that interference requires the same neural circuits to be engaged in the two tasks and provoke competing processes of synaptic plasticity. To test this, subjects learned a ballistic ankle plantarflexion task. Early motor memory...... was disrupted by subsequent learning of a precision tracking task with the same agonist muscle group, but not by learning involving antagonist muscles or by voluntary agonist contractions that did not require learning. If the competing task was learned with the same agonist muscle group 4 hours following...

Out-of-band and adjacent-channel interference reduction by analog nonlinear filters

Science.gov (United States)

Nikitin, Alexei V.; Davidchack, Ruslan L.; Smith, Jeffrey E.

2015-12-01

In a perfect world, we would have `brick wall' filters, no-distortion amplifiers and mixers, and well-coordinated spectrum operations. The real world, however, is prone to various types of unintentional and intentional interference of technogenic (man-made) origin that can disrupt critical communication systems. In this paper, we introduce a methodology for mitigating technogenic interference in communication channels by analog nonlinear filters, with an emphasis on the mitigation of out-of-band and adjacent-channel interference. Interference induced in a communications receiver by external transmitters can be viewed as wide-band non-Gaussian noise affecting a narrower-band signal of interest. This noise may contain a strong component within the receiver passband, which may dominate over the thermal noise. While the total wide-band interference seen by the receiver may or may not be impulsive, we demonstrate that the interfering component due to power emitted by the transmitter into the receiver channel is likely to appear impulsive under a wide range of conditions. We give an example of mechanisms of impulsive interference in digital communication systems resulting from the nonsmooth nature of any physically realizable modulation scheme for transmission of a digital (discontinuous) message. We show that impulsive interference can be effectively mitigated by nonlinear differential limiters (NDLs). An NDL can be configured to behave linearly when the input signal does not contain outliers. When outliers are encountered, the nonlinear response of the NDL limits the magnitude of the respective outliers in the output signal. The signal quality is improved in excess of that achievable by the respective linear filter, increasing the capacity of a communications channel. The behavior of an NDL, and its degree of nonlinearity, is controlled by a single parameter in a manner that enables significantly better overall suppression of the noise-containing impulsive components

Who Needs Replication?

Science.gov (United States)

Porte, Graeme

2013-01-01

In this paper, the editor of a recent Cambridge University Press book on research methods discusses replicating previous key studies to throw more light on their reliability and generalizability. Replication research is presented as an accepted method of validating previous research by providing comparability between the original and replicated…

Mechanisms of bacterial DNA replication restart

Science.gov (United States)

Windgassen, Tricia A; Wessel, Sarah R; Bhattacharyya, Basudeb

2018-01-01

Abstract Multi-protein DNA replication complexes called replisomes perform the essential process of copying cellular genetic information prior to cell division. Under ideal conditions, replisomes dissociate only after the entire genome has been duplicated. However, DNA replication rarely occurs without interruptions that can dislodge replisomes from DNA. Such events produce incompletely replicated chromosomes that, if left unrepaired, prevent the segregation of full genomes to daughter cells. To mitigate this threat, cells have evolved ‘DNA replication restart’ pathways that have been best defined in bacteria. Replication restart requires recognition and remodeling of abandoned replication forks by DNA replication restart proteins followed by reloading of the replicative DNA helicase, which subsequently directs assembly of the remaining replisome subunits. This review summarizes our current understanding of the mechanisms underlying replication restart and the proteins that drive the process in Escherichia coli (PriA, PriB, PriC and DnaT). PMID:29202195

Supplementary Material for: CRISPR/Cas9-mediated viral interference in plants

KAUST Repository

Ali, Zahir; Abulfaraj, Aala A.; Idris, Ali; Ali, Shakila; Tashkandi, Manal; Mahfouz, Magdy

2015-01-01

Abstract Background The CRISPR/Cas9 system provides bacteria and archaea with molecular immunity against invading phages and conjugative plasmids. Recently, CRISPR/Cas9 has been used for targeted genome editing in diverse eukaryotic species. Results In this study, we investigate whether the CRISPR/Cas9 system could be used in plants to confer molecular immunity against DNA viruses. We deliver sgRNAs specific for coding and non-coding sequences of tomato yellow leaf curl virus (TYLCV) into Nicotiana benthamiana plants stably overexpressing the Cas9 endonuclease, and subsequently challenge these plants with TYLCV. Our data demonstrate that the CRISPR/Cas9 system targeted TYLCV for degradation and introduced mutations at the target sequences. All tested sgRNAs exhibit interference activity, but those targeting the stem-loop sequence within the TYLCV origin of replication in the intergenic region (IR) are the most effective. N. benthamiana plants expressing CRISPR/Cas9 exhibit delayed or reduced accumulation of viral DNA, abolishing or significantly attenuating symptoms of infection. Moreover, this system could simultaneously target multiple DNA viruses. Conclusions These data establish the efficacy of the CRISPR/Cas9 system for viral interference in plants, thereby extending the utility of this technology and opening the possibility of producing plants resistant to multiple viral infections.

What Should Researchers Expect When They Replicate Studies? A Statistical View of Replicability in Psychological Science.

Science.gov (United States)

Patil, Prasad; Peng, Roger D; Leek, Jeffrey T

2016-07-01

A recent study of the replicability of key psychological findings is a major contribution toward understanding the human side of the scientific process. Despite the careful and nuanced analysis reported, the simple narrative disseminated by the mass, social, and scientific media was that in only 36% of the studies were the original results replicated. In the current study, however, we showed that 77% of the replication effect sizes reported were within a 95% prediction interval calculated using the original effect size. Our analysis suggests two critical issues in understanding replication of psychological studies. First, researchers' intuitive expectations for what a replication should show do not always match with statistical estimates of replication. Second, when the results of original studies are very imprecise, they create wide prediction intervals-and a broad range of replication effects that are consistent with the original estimates. This may lead to effects that replicate successfully, in that replication results are consistent with statistical expectations, but do not provide much information about the size (or existence) of the true effect. In this light, the results of the Reproducibility Project: Psychology can be viewed as statistically consistent with what one might expect when performing a large-scale replication experiment. © The Author(s) 2016.

OFDM with Index Modulation for Asynchronous mMTC Networks.

Science.gov (United States)

Doğan, Seda; Tusha, Armed; Arslan, Hüseyin

2018-04-21

One of the critical missions for next-generation wireless communication systems is to fulfill the high demand for massive Machine-Type Communications (mMTC). In mMTC systems, a sporadic transmission is performed between machine users and base station (BS). Lack of coordination between the users and BS in time destroys orthogonality between the subcarriers, and causes inter-carrier interference (ICI). Therefore, providing services to asynchronous massive machine users is a major challenge for Orthogonal Frequency Division Multiplexing (OFDM). In this study, OFDM with index modulation (OFDM-IM) is proposed as an eligible solution to alleviate ICI caused by asynchronous transmission in uncoordinated mMTC networks. In OFDM-IM, data transmission is performed not only by modulated subcarriers but also by the indices of active subcarriers. Unlike classical OFDM, fractional subcarrier activation leads to less ICI in OFDM-IM technology. A novel subcarrier mapping scheme (SMS) named as Inner Subcarrier Activation is proposed to further alleviate adjacent user interference in asynchronous OFDM-IM-based systems. ISA reduces inter-user interference since it gives more activation priority to inner subcarriers compared with the existing SMS-s. The superiority of the proposed SMS is shown through both theoretical analysis and computer-based simulations in comparison to existing mapping schemes for asynchronous systems.

Identification of Host Cell Factors Associated with Astrovirus Replication in Caco-2 Cells.

Science.gov (United States)

Murillo, Andrea; Vera-Estrella, Rosario; Barkla, Bronwyn J; Méndez, Ernesto; Arias, Carlos F

2015-10-01

Astroviruses are small, nonenveloped viruses with a single-stranded positive-sense RNA genome causing acute gastroenteritis in children and immunocompromised patients. Since positive-sense RNA viruses have frequently been found to replicate in association with membranous structures, in this work we characterized the replication of the human astrovirus serotype 8 strain Yuc8 in Caco-2 cells, using density gradient centrifugation and free-flow zonal electrophoresis (FFZE) to fractionate cellular membranes. Structural and nonstructural viral proteins, positive- and negative-sense viral RNA, and infectious virus particles were found to be associated with a distinct population of membranes separated by FFZE. The cellular proteins associated with this membrane population in infected and mock-infected cells were identified by tandem mass spectrometry. The results indicated that membranes derived from multiple cell organelles were present in the population. Gene ontology and protein-protein interaction network analysis showed that groups of proteins with roles in fatty acid synthesis and ATP biosynthesis were highly enriched in the fractions of this population in infected cells. Based on this information, we investigated by RNA interference the role that some of the identified proteins might have in the replication cycle of the virus. Silencing of the expression of genes involved in cholesterol (DHCR7, CYP51A1) and fatty acid (FASN) synthesis, phosphatidylinositol (PI4KIIIβ) and inositol phosphate (ITPR3) metabolism, and RNA helicase activity (DDX23) significantly decreased the amounts of Yuc8 genomic and antigenomic RNA, synthesis of the structural protein VP90, and virus yield. These results strongly suggest that astrovirus RNA replication and particle assembly take place in association with modified membranes potentially derived from multiple cell organelles. Astroviruses are common etiological agents of acute gastroenteritis in children and immunocompromised patients

Identification of Host Cell Factors Associated with Astrovirus Replication in Caco-2 Cells

Science.gov (United States)

Murillo, Andrea; Vera-Estrella, Rosario; Barkla, Bronwyn J.; Méndez, Ernesto

2015-01-01

ABSTRACT Astroviruses are small, nonenveloped viruses with a single-stranded positive-sense RNA genome causing acute gastroenteritis in children and immunocompromised patients. Since positive-sense RNA viruses have frequently been found to replicate in association with membranous structures, in this work we characterized the replication of the human astrovirus serotype 8 strain Yuc8 in Caco-2 cells, using density gradient centrifugation and free-flow zonal electrophoresis (FFZE) to fractionate cellular membranes. Structural and nonstructural viral proteins, positive- and negative-sense viral RNA, and infectious virus particles were found to be associated with a distinct population of membranes separated by FFZE. The cellular proteins associated with this membrane population in infected and mock-infected cells were identified by tandem mass spectrometry. The results indicated that membranes derived from multiple cell organelles were present in the population. Gene ontology and protein-protein interaction network analysis showed that groups of proteins with roles in fatty acid synthesis and ATP biosynthesis were highly enriched in the fractions of this population in infected cells. Based on this information, we investigated by RNA interference the role that some of the identified proteins might have in the replication cycle of the virus. Silencing of the expression of genes involved in cholesterol (DHCR7, CYP51A1) and fatty acid (FASN) synthesis, phosphatidylinositol (PI4KIIIβ) and inositol phosphate (ITPR3) metabolism, and RNA helicase activity (DDX23) significantly decreased the amounts of Yuc8 genomic and antigenomic RNA, synthesis of the structural protein VP90, and virus yield. These results strongly suggest that astrovirus RNA replication and particle assembly take place in association with modified membranes potentially derived from multiple cell organelles. IMPORTANCE Astroviruses are common etiological agents of acute gastroenteritis in children and

Sleep can reduce proactive interference.

Science.gov (United States)

Abel, Magdalena; Bäuml, Karl-Heinz T

2014-01-01

Sleep has repeatedly been connected to processes of memory consolidation. While extensive research indeed documents beneficial effects of sleep on memory, little is yet known about the role of sleep for interference effects in episodic memory. Although two prior studies reported sleep to reduce retroactive interference, no sleep effect has previously been found for proactive interference. Here we applied a study format differing from that employed by the prior studies to induce a high degree of proactive interference, and asked participants to encode a single list or two interfering lists of paired associates via pure study cycles. Testing occurred after 12 hours of diurnal wakefulness or nocturnal sleep. Consistent with the prior work, we found sleep in comparison to wake did not affect memory for the single list, but reduced retroactive interference. In addition we found sleep reduced proactive interference, and reduced retroactive and proactive interference to the same extent. The finding is consistent with the view that arising benefits of sleep are caused by the reactivation of memory contents during sleep, which has been suggested to strengthen and stabilise memories. Such stabilisation may make memories less susceptible to competition from interfering memories at test and thus reduce interference effects.

Interferenceless coded aperture correlation holography-a new technique for recording incoherent digital holograms without two-wave interference.

Science.gov (United States)

Vijayakumar, A; Rosen, Joseph

2017-06-12

Recording digital holograms without wave interference simplifies the optical systems, increases their power efficiency and avoids complicated aligning procedures. We propose and demonstrate a new technique of digital hologram acquisition without two-wave interference. Incoherent light emitted from an object propagates through a random-like coded phase mask and recorded directly without interference by a digital camera. In the training stage of the system, a point spread hologram (PSH) is first recorded by modulating the light diffracted from a point object by the coded phase masks. At least two different masks should be used to record two different intensity distributions at all possible axial locations. The various recorded patterns at every axial location are superposed in the computer to obtain a complex valued PSH library cataloged to its axial location. Following the training stage, an object is placed within the axial boundaries of the PSH library and the light diffracted from the object is once again modulated by the same phase masks. The intensity patterns are recorded and superposed exactly as the PSH to yield a complex hologram of the object. The object information at any particular plane is reconstructed by a cross-correlation between the complex valued hologram and the appropriate element of the PSH library. The characteristics and the performance of the proposed system were compared with an equivalent regular imaging system.

MCS and sub-band selection for downlink interference coordination in LTE-A Femtocells

OpenAIRE

Muñoz Medina, Olga; Agustín de Dios, Adrián; Vidal Manzano, José

2012-01-01

This paper proposes a decentralized algorithm for interference coordination in LTE-A networks, based on the exchange of information (pricing) at control plane level. In our approach, every user equipment (UE) report the maximum modulation and coding scheme (MCS) that can be used within several sets (sub-bands) of available resource blocks, along with a parameter (cost) that measures the MCS degradation due to the transmission from an interfering neighbor. Through the e...

Dark Matter Interference

DEFF Research Database (Denmark)

Del Nobile, Eugenio; Kouvaris, Christoforos; Sannino, Francesco

2012-01-01

We study different patterns of interference in WIMP-nuclei elastic scattering that can accommodate the DAMA and CoGeNT experiments via an isospin violating ratio $f_n/f_p=-0.71$. We study interference between the following pairs of mediators: Z and Z', Z' and Higgs, and two Higgs fields. We show ...

HIV-1 Replication and the Cellular Eukaryotic Translation Apparatus

Directory of Open Access Journals (Sweden)

Santiago Guerrero

2015-01-01

Full Text Available Eukaryotic translation is a complex process composed of three main steps: initiation, elongation, and termination. During infections by RNA- and DNA-viruses, the eukaryotic translation machinery is used to assure optimal viral protein synthesis. Human immunodeficiency virus type I (HIV-1 uses several non-canonical pathways to translate its own proteins, such as leaky scanning, frameshifting, shunt, and cap-independent mechanisms. Moreover, HIV-1 modulates the host translation machinery by targeting key translation factors and overcomes different cellular obstacles that affect protein translation. In this review, we describe how HIV-1 proteins target several components of the eukaryotic translation machinery, which consequently improves viral translation and replication.

DNA Replication Profiling Using Deep Sequencing.

Science.gov (United States)

Saayman, Xanita; Ramos-Pérez, Cristina; Brown, Grant W

2018-01-01

Profiling of DNA replication during progression through S phase allows a quantitative snap-shot of replication origin usage and DNA replication fork progression. We present a method for using deep sequencing data to profile DNA replication in S. cerevisiae.

Histone deacetylase inhibitors improve the replication of oncolytic herpes simplex virus in breast cancer cells.

Directory of Open Access Journals (Sweden)

James J Cody

Full Text Available New therapies are needed for metastatic breast cancer patients. Oncolytic herpes simplex virus (oHSV is an exciting therapy being developed for use against aggressive tumors and established metastases. Although oHSV have been demonstrated safe in clinical trials, a lack of sufficient potency has slowed the clinical application of this approach. We utilized histone deacetylase (HDAC inhibitors, which have been noted to impair the innate antiviral response and improve gene transcription from viral vectors, to enhance the replication of oHSV in breast cancer cells. A panel of chemically diverse HDAC inhibitors were tested at three different doses (LD50 for their ability to modulate the replication of oHSV in breast cancer cells. Several of the tested HDAC inhibitors enhanced oHSV replication at low multiplicity of infection (MOI following pre-treatment of the metastatic breast cancer cell line MDA-MB-231 and the oHSV-resistant cell line 4T1, but not in the normal breast epithelial cell line MCF10A. Inhibitors of class I HDACs, including pan-selective compounds, were more effective for increasing oHSV replication compared to inhibitors that selectively target class II HDACs. These studies demonstrate that select HDAC inhibitors increase oHSV replication in breast cancer cells and provides support for pre-clinical evaluation of this combination strategy.

MITA/STING and Its Alternative Splicing Isoform MRP Restrict Hepatitis B Virus Replication.

Science.gov (United States)

Liu, Shuhui; Zhao, Kaitao; Su, Xi; Lu, Lu; Zhao, He; Zhang, Xianwen; Wang, Yun; Wu, Chunchen; Chen, Jizheng; Zhou, Yuan; Hu, Xue; Wang, Yanyi; Lu, Mengji; Chen, Xinwen; Pei, Rongjuan

2017-01-01

An efficient clearance of hepatitis B virus (HBV) requires the coordinated work of both the innate and adaptive immune responses. MITA/STING, an adapter protein of the innate immune signaling pathways, plays a key role in regulating innate and adaptive immune responses to DNA virus infection. Previously, we identified an alternatively spliced isoform of MITA/STING, called MITA-related protein (MRP), and found that MRP could specifically block MITA-mediated interferon (IFN) induction while retaining the ability to activate NF-κB. Here, we asked whether MITA/STING and MRP were able to control the HBV replication. Both MITA/STING and MRP significantly inhibited HBV replication in vitro. MITA overexpression stimulated IRF3-IFN pathway; while MRP overexpression activated NF-κB pathway, suggesting these two isoforms may inhibit HBV replication through different ways. Using a hydrodynamic injection (HI) mouse model, we found that HBV replication was reduced following MITA/STING and MRP expression vectors in mice and was enhanced by the knockout of MITA/STING (MITA/STING-/-). The HBV specific humoral and CD8+ T cell responses were impaired in MITA/STING deficient mice, suggesting the participation of MITA/STING in the initiation of host adaptive immune responses. In summary, our data suggest that MITA/STING and MRP contribute to HBV control via modulation of the innate and adaptive responses.

A Defective Interfering Influenza RNA Inhibits Infectious Influenza Virus Replication in Human Respiratory Tract Cells: A Potential New Human Antiviral

Directory of Open Access Journals (Sweden)

Claire M. Smith

2016-08-01

Full Text Available Defective interfering (DI viruses arise during the replication of influenza A virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. In this study we hypothesise that a cloned DI influenza A virus RNA may prevent infection of human respiratory epithelial cells with infection by influenza A. The DI RNA (244/PR8 was derived by a natural deletion process from segment 1 of influenza A/PR/8/34 (H1N1; it comprises 395 nucleotides and is packaged in the DI virion in place of a full-length genome segment 1. Given intranasally, 244/PR8 DI virus protects mice and ferrets from clinical influenza caused by a number of different influenza A subtypes and interferes with production of infectious influenza A virus in cells in culture. However, evidence that DI influenza viruses are active in cells of the human respiratory tract is lacking. Here we show that 244/PR8 DI RNA is replicated by an influenza A challenge virus in human lung diploid fibroblasts, bronchial epithelial cells, and primary nasal basal cells, and that the yield of challenge virus is significantly reduced in a dose-dependent manner indicating that DI influenza virus has potential as a human antiviral.

Studying and comparing spectrum efficiency and error probability in GMSK and DBPSK modulation schemes

Directory of Open Access Journals (Sweden)

Juan Mario Torres Nova

2008-09-01

Full Text Available Gaussian minimum shift keying (GMSK and differential binary phase shift keying (DBPSK are two digital modulation schemes which are -frequently used in radio communication systems; however, there is interdependence in the use of its benefits (spectral efficiency, low bit error rate, low inter symbol interference, etc. Optimising one parameter creates problems for another; for example, the GMSK scheme succeeds in reducing bandwidth when introducing a Gaussian filter into an MSK (minimum shift ke-ying modulator in exchange for increasing inter-symbol interference in the system. The DBPSK scheme leads to lower error pro-bability, occupying more bandwidth; it likewise facilitates synchronous data transmission due to the receiver’s bit delay when re-covering a signal.

RNA interference inhibits herpes simplex virus type 1 isolated from saliva samples and mucocutaneous lesions.

Science.gov (United States)

Silva, Amanda Perse da; Lopes, Juliana Freitas; Paula, Vanessa Salete de

2014-01-01

The aim of this study was to evaluate the use of RNA interference to inhibit herpes simplex virus type-1 replication in vitro. For herpes simplex virus type-1 gene silencing, three different small interfering RNAs (siRNAs) targeting the herpes simplex virus type-1 UL39 gene (sequence si-UL 39-1, si-UL 39-2, and si-UL 39-3) were used, which encode the large subunit of ribonucleotide reductase, an essential enzyme for DNA synthesis. Herpes simplex virus type-1 was isolated from saliva samples and mucocutaneous lesions from infected patients. All mucocutaneous lesions' samples were positive for herpes simplex virus type-1 by real-time PCR and by virus isolation; all herpes simplex virus type-1 from saliva samples were positive by real-time PCR and 50% were positive by virus isolation. The levels of herpes simplex virus type-1 DNA remaining after siRNA treatment were assessed by real-time PCR, whose results demonstrated that the effect of siRNAs on gene expression depends on siRNA concentration. The three siRNA sequences used were able to inhibit viral replication, assessed by real-time PCR and plaque assays and among them, the sequence si-UL 39-1 was the most effective. This sequence inhibited 99% of herpes simplex virus type-1 replication. The results demonstrate that silencing herpes simplex virus type-1 UL39 expression by siRNAs effectively inhibits herpes simplex virus type-1 replication, suggesting that siRNA based antiviral strategy may be a potential therapeutic alternative. Copyright © 2014. Published by Elsevier Editora Ltda.

Single-beam image encryption using spatially separated ciphertexts based on interference principle in the Fresnel domain

Science.gov (United States)

Wang, Qu; Guo, Qing; Lei, Liang; Zhou, Jinyun

2014-12-01

A new optical security system for image encryption based on optical interference principle and translation property of Fresnel transform (FrT) has been proposed in this article. The algorithm of this proposal is specially designed for single-beam optical decryption and can thoroughly resolve the silhouette problem existing in the previous interference-based scheme. Different from earlier schemes using interference of phase-only masks (POMs), the inverse FrT of primitive image is digitally decomposed into a random POM and a complex field distribution. Information associated with the primitive images can be completely smoothed away by the modulation of this random POM. Through the translation property of FrT, two linear phase-only terms are then used to modulate the obtained random POM and the complex distribution, respectively. Two complex ciphertexts are generated by performing digital inverse FrT again. One cannot recover any visible information of secret image using only one ciphertext. Moreover, to recover the primitive image correctly, the correct ciphertexts must be placed in the certain positions of input plane of decryption system, respectively. As additional keys, position center coordinates of ciphertexts can increase the security strength of this encryption system against brute force attacks greatly. Numerical simulations have been given to verify the performance and feasibility of this proposal. To further enhance the application value of this algorithm, an alternative approach based on Fourier transform has also been discussed briefly.

Enhancing quantum effects via periodic modulations in optomechanical systems

Science.gov (United States)

Farace, Alessandro; Giovannetti, Vittorio

2012-07-01

Parametrically modulated optomechanical systems have been recently proposed as a simple and efficient setting for the quantum control of a micromechanical oscillator: relevant possibilities include the generation of squeezing in the oscillator position (or momentum) and the enhancement of entanglement between mechanical and radiation modes. In this paper we further investigate this modulation regime, considering an optomechanical system with one or more parameters being modulated over time. We first apply a sinusoidal modulation of the mechanical frequency and characterize the optimal regime in which the visibility of purely quantum effects is maximal. We then introduce a second modulation on the input laser intensity and analyze the interplay between the two. We find that an interference pattern shows up, so that different choices of the relative phase between the two modulations can either enhance or cancel the desired quantum effects, opening new possibilities for optimal quantum control strategies.

Induction of UV-resistant DNA replication in Escherichia coli: Induced stable DNA replication as an SOS function

International Nuclear Information System (INIS)

Kogoma, T.; Torrey, T.A.; Connaughton, M.J.

1979-01-01

The striking similarity between the treatments that induce SOS functions and those that result in stable DNA replication (continuous DNA replication in the absence of protein synthesis) prompted us to examine the possibility of stable DNA replication being a recA + lexA + -dependent SOS function. In addition to the treatments previously reported, ultraviolet (UV) irradiation or treatment with mitomycin C was also found to induce stable DNA replication. The thermal treatment of tif-1 strains did not result in detectable levels of stable DNA replication, but nalidixic acid readily induced the activity in these strains. The induction of stable DNA replication with nalidixic acid was severely suppressed in tif-1 lex A mutant strains. The inhibitory activity of lexA3 was negated by the presence of the spr-5l mutation, an intragenic suppressor of lexA3. Induced stable DNA replication was found to be considerably more resistant to UV irradiation than normal replication both in a uvr A6 strain and a uvr + strain. The UV-resistant replication occurred mostly in the semiconservative manner. The possible roles of stable DNA replication in repair of damaged DNA are discussed. (orig.)

Acousto-optic replication of ultrashort laser pulses

Science.gov (United States)

Yushkov, Konstantin B.; Molchanov, Vladimir Ya.; Ovchinnikov, Andrey V.; Chefonov, Oleg V.

2017-10-01

Precisely controlled sequences of ultrashort laser pulses are required in various scientific and engineering applications. We developed a phase-only acousto-optic pulse shaping method for replication of ultrashort laser pulses in a TW laser system. A sequence of several Fourier-transform-limited pulses is generated from a single femtosecond laser pulse by means of applying a piecewise linear phase modulation over the whole emission spectrum. Analysis demonstrates that the main factor which limits maximum delay between the pulse replicas is spectral resolution of the acousto-optic dispersive delay line used for pulse shaping. In experiments with a Cr:forsterite laser system, we obtained delays from 0.3 to 3.5 ps between two replicas of 190 fs transform-limited pulses at the central wavelength of laser emission, 1230 nm.

Downlink Error Rates of Half-duplex Users in Full-duplex Networks over a Laplacian Inter-User Interference Limited and EGK fading

KAUST Repository

Soury, Hamza

2017-03-14

This paper develops a mathematical framework to study downlink error rates and throughput for half-duplex (HD) terminals served by a full-duplex (FD) base station (BS). The developed model is used to motivate long term pairing for users that have non-line of sight (NLOS) interfering link. Consequently, we study the interferer limited problem that appears between NLOS HD users-pair that are scheduled on the same FD channel. The distribution of the interference is first characterized via its distribution function, which is derived in closed form. Then, a comprehensive performance assessment for the proposed pairing scheme is provided by assuming Extended Generalized- $cal{K}$ (EGK) fading for the downlink and studying different modulation schemes. To this end, a unified closed form expression for the average symbol error rate is derived. Furthermore, we show the effective downlink throughput gain harvested by the pairing NLOS users as a function of the average signal-to-interferenceratio when compared to an idealized HD scenario with neither interference nor noise. Finally, we show the minimum required channel gain pairing threshold to harvest downlink throughput via the FD operation when compared to the HD case for each modulation scheme.

Interference and Sensitivity Analysis.

Science.gov (United States)

VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J; Halloran, M Elizabeth

2014-11-01

Causal inference with interference is a rapidly growing area. The literature has begun to relax the "no-interference" assumption that the treatment received by one individual does not affect the outcomes of other individuals. In this paper we briefly review the literature on causal inference in the presence of interference when treatments have been randomized. We then consider settings in which causal effects in the presence of interference are not identified, either because randomization alone does not suffice for identification, or because treatment is not randomized and there may be unmeasured confounders of the treatment-outcome relationship. We develop sensitivity analysis techniques for these settings. We describe several sensitivity analysis techniques for the infectiousness effect which, in a vaccine trial, captures the effect of the vaccine of one person on protecting a second person from infection even if the first is infected. We also develop two sensitivity analysis techniques for causal effects in the presence of unmeasured confounding which generalize analogous techniques when interference is absent. These two techniques for unmeasured confounding are compared and contrasted.

Radio Frequency Identification (RFID) in medical environment: Gaussian Derivative Frequency Modulation (GDFM) as a novel modulation technique with minimal interference properties.

Science.gov (United States)

Rieche, Marie; Komenský, Tomás; Husar, Peter

2011-01-01

Radio Frequency Identification (RFID) systems in healthcare facilitate the possibility of contact-free identification and tracking of patients, medical equipment and medication. Thereby, patient safety will be improved and costs as well as medication errors will be reduced considerably. However, the application of RFID and other wireless communication systems has the potential to cause harmful electromagnetic disturbances on sensitive medical devices. This risk mainly depends on the transmission power and the method of data communication. In this contribution we point out the reasons for such incidents and give proposals to overcome these problems. Therefore a novel modulation and transmission technique called Gaussian Derivative Frequency Modulation (GDFM) is developed. Moreover, we carry out measurements to show the inteference properties of different modulation schemes in comparison to our GDFM.

Chromatin replication and epigenome maintenance

DEFF Research Database (Denmark)

Alabert, Constance; Groth, Anja

2012-01-01

Stability and function of eukaryotic genomes are closely linked to chromatin structure and organization. During cell division the entire genome must be accurately replicated and the chromatin landscape reproduced on new DNA. Chromatin and nuclear structure influence where and when DNA replication...... initiates, whereas the replication process itself disrupts chromatin and challenges established patterns of genome regulation. Specialized replication-coupled mechanisms assemble new DNA into chromatin, but epigenome maintenance is a continuous process taking place throughout the cell cycle. If DNA...

36 CFR 910.64 - Replication.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Replication. 910.64 Section 910.64 Parks, Forests, and Public Property PENNSYLVANIA AVENUE DEVELOPMENT CORPORATION GENERAL... DEVELOPMENT AREA Glossary of Terms § 910.64 Replication. Replication means the process of using modern methods...

Multiple-Antenna Interference Cancellation for WLAN with MAC Interference Avoidance in Open Access Networks

Directory of Open Access Journals (Sweden)

Alexandr M. Kuzminskiy

2007-10-01

Full Text Available The potential of multiantenna interference cancellation receiver algorithms for increasing the uplink throughput in WLAN systems such as 802.11 is investigated. The medium access control (MAC in such systems is based on carrier sensing multiple-access with collision avoidance (CSMA/CA, which itself is a powerful tool for the mitigation of intrasystem interference. However, due to the spatial dependence of received signal strengths, it is possible for the collision avoidance mechanism to fail, resulting in packet collisions at the receiver and a reduction in system throughput. The CSMA/CA MAC protocol can be complemented in such scenarios by interference cancellation (IC algorithms at the physical (PHY layer. The corresponding gains in throughput are a result of the complex interplay between the PHY and MAC layers. It is shown that semiblind interference cancellation techniques are essential for mitigating the impact of interference bursts, in particular since these are typically asynchronous with respect to the desired signal burst. Semiblind IC algorithms based on second- and higher-order statistics are compared to the conventional no-IC and training-based IC techniques in an open access network (OAN scenario involving home and visiting users. It is found that the semiblind IC algorithms significantly outperform the other techniques due to the bursty and asynchronous nature of the interference caused by the MAC interference avoidance scheme.

Multiple-Antenna Interference Cancellation for WLAN with MAC Interference Avoidance in Open Access Networks

Directory of Open Access Journals (Sweden)

Kuzminskiy Alexandr M

2007-01-01

Full Text Available The potential of multiantenna interference cancellation receiver algorithms for increasing the uplink throughput in WLAN systems such as 802.11 is investigated. The medium access control (MAC in such systems is based on carrier sensing multiple-access with collision avoidance (CSMA/CA, which itself is a powerful tool for the mitigation of intrasystem interference. However, due to the spatial dependence of received signal strengths, it is possible for the collision avoidance mechanism to fail, resulting in packet collisions at the receiver and a reduction in system throughput. The CSMA/CA MAC protocol can be complemented in such scenarios by interference cancellation (IC algorithms at the physical (PHY layer. The corresponding gains in throughput are a result of the complex interplay between the PHY and MAC layers. It is shown that semiblind interference cancellation techniques are essential for mitigating the impact of interference bursts, in particular since these are typically asynchronous with respect to the desired signal burst. Semiblind IC algorithms based on second- and higher-order statistics are compared to the conventional no-IC and training-based IC techniques in an open access network (OAN scenario involving home and visiting users. It is found that the semiblind IC algorithms significantly outperform the other techniques due to the bursty and asynchronous nature of the interference caused by the MAC interference avoidance scheme.

Investigating the role of viral integral membrane proteins in promoting the assembly of nepovirus and comovirus replication factories

Directory of Open Access Journals (Sweden)

Helene eSanfacon

2013-01-01

Full Text Available Formation of plant virus membrane-associated replication factories requires the association of viral replication proteins and viral RNA with intracellular membranes, the recruitment of host factors and the modification of membranes to form novel structures that house the replication complex. Many viruses encode integral membrane proteins that act as anchors for the replication complex. These hydrophobic proteins contain trans-membrane domains and/or amphipathic helices that associate with the membrane and modify its structure. The comovirus Co-Pro and NTP-binding (NTB, putative helicase proteins and the cognate nepovirus X2 and NTB proteins are among the best characterized plant virus integral membrane replication proteins and are functionally related to the picornavirus 2B, 2C and 3A membrane proteins. The identification of membrane-association domains and analysis of the membrane topology of these proteins is discussed. The evidence suggesting that these proteins have the ability to induce membrane proliferation, alter the structure and integrity of intracellular membranes and modulate the induction of symptoms in infected plants is also reviewed. Finally, areas of research that need further investigation are highlighted.

Replication stress-induced chromosome breakage is correlated with replication fork progression and is preceded by single-stranded DNA formation.

Science.gov (United States)

Feng, Wenyi; Di Rienzi, Sara C; Raghuraman, M K; Brewer, Bonita J

2011-10-01

Chromosome breakage as a result of replication stress has been hypothesized to be the direct consequence of defective replication fork progression, or "collapsed" replication forks. However, direct and genome-wide evidence that collapsed replication forks give rise to chromosome breakage is still lacking. Previously we showed that a yeast replication checkpoint mutant mec1-1, after transient exposure to replication impediment imposed by hydroxyurea (HU), failed to complete DNA replication, accumulated single-stranded DNA (ssDNA) at the replication forks, and fragmented its chromosomes. In this study, by following replication fork progression genome-wide via ssDNA detection and by direct mapping of chromosome breakage after HU exposure, we have tested the hypothesis that the chromosome breakage in mec1 cells occurs at collapsed replication forks. We demonstrate that sites of chromosome breakage indeed correlate with replication fork locations. Moreover, ssDNA can be detected prior to chromosome breakage, suggesting that ssDNA accumulation is the common precursor to double strand breaks at collapsed replication forks.

Collision-induced destructive quantum interference

International Nuclear Information System (INIS)

Yang Xihua; Sun Zhenrong; Zhang Shi'an; Ding Liang'en; Wang Zugeng

2005-01-01

We conduct theoretical studies on the collision-induced destructive quantum interference of two-colour two-photon transitions in an open rhomb-type five-level system with a widely separated doublet by the density matrix approach. The effects of the collision-induced decay rates, the ratio of the transition dipole moments and the energy separation of the doublet on the interference are analysed. It is shown that a narrow dip appears in the excitation spectrum due to the collision-induced destructive interference, and that the narrow interference dip still exists even when the collision broadening is comparable to the energy separation of the doublet. The physical origin of the collision-induced destructive quantum interference is analysed in the dressed-atom picture

Replication Research and Special Education

Science.gov (United States)

Travers, Jason C.; Cook, Bryan G.; Therrien, William J.; Coyne, Michael D.

2016-01-01

Replicating previously reported empirical research is a necessary aspect of an evidence-based field of special education, but little formal investigation into the prevalence of replication research in the special education research literature has been conducted. Various factors may explain the lack of attention to replication of special education…

Eukaryotic DNA Replication Fork.

Science.gov (United States)

Burgers, Peter M J; Kunkel, Thomas A

2017-06-20

This review focuses on the biogenesis and composition of the eukaryotic DNA replication fork, with an emphasis on the enzymes that synthesize DNA and repair discontinuities on the lagging strand of the replication fork. Physical and genetic methodologies aimed at understanding these processes are discussed. The preponderance of evidence supports a model in which DNA polymerase ε (Pol ε) carries out the bulk of leading strand DNA synthesis at an undisturbed replication fork. DNA polymerases α and δ carry out the initiation of Okazaki fragment synthesis and its elongation and maturation, respectively. This review also discusses alternative proposals, including cellular processes during which alternative forks may be utilized, and new biochemical studies with purified proteins that are aimed at reconstituting leading and lagging strand DNA synthesis separately and as an integrated replication fork.

The progression of replication forks at natural replication barriers in live bacteria

NARCIS (Netherlands)

Moolman, M.C.; Tiruvadi Krishnan, S; Kerssemakers, J.W.J.; de Leeuw, R.; Lorent, V.J.F.; Sherratt, David J.; Dekker, N.H.

2016-01-01

Protein-DNA complexes are one of the principal barriers the replisome encounters during replication. One such barrier is the Tus-ter complex, which is a direction dependent barrier for replication fork progression. The details concerning the dynamics of the replisome when encountering these

Enterovirus 71 induces autophagy by regulating has-miR-30a expression to promote viral replication.

Science.gov (United States)

Fu, Yuxuan; Xu, Wentao; Chen, Deyan; Feng, Chunhong; Zhang, Li; Wang, Xiaohui; Lv, Xiaowen; Zheng, Nan; Jin, Yu; Wu, Zhiwei

2015-12-01

Enterovirus 71 (EV71), the etiological agent of hand-foot-and-mouth disease, has increasingly become a public health challenge around the world. Previous studies reported that EV71 infection can induce autophagic machinery to enhance viral replication in vitro and in vivo, but did not address the underlying mechanisms. Increasing evidence suggests that autophagy, in a virus-specific manner, may function to degrade viruses or facilitate viral replication. In this study, we reported that EV71 infection of human epidermoid carcinoma (Hep2) and African green monkey kidney cells (Vero) induced autophagy, which is beneficial for viral replication. Our investigation of the mechanisms revealed that EV71 infection resulted in the reduction of cellular miR-30a, which led to the inhibition of Beclin-1, a key autophagy-promoting gene that plays important roles at the early phase of autophagosome formation. We provided further evidence that by modulating cellular miR-30a level through either overexpression or inhibition, one can inhibit or promote EV71 replication, respectively, through regulating autophagic activity. Copyright © 2015 Elsevier B.V. All rights reserved.

Flock House virus subgenomic RNA3 is replicated and its replication correlates with transactivation of RNA2

International Nuclear Information System (INIS)

Eckerle, Lance D.; Albarino, Cesar G.; Ball, L. Andrew.

2003-01-01

The nodavirus Flock House virus has a bipartite genome composed of RNAs 1 and 2, which encode the catalytic component of the RNA-dependent RNA polymerase (RdRp) and the capsid protein precursor, respectively. In addition to catalyzing replication of the viral genome, the RdRp also transcribes from RNA1 a subgenomic RNA3, which is both required for and suppressed by RNA2 replication. Here, we show that in the absence of RNA1 replication, FHV RdRp replicated positive-sense RNA3 transcripts fully and copied negative-sense RNA3 transcripts into positive strands. The two nonstructural proteins encoded by RNA3 were dispensable for replication, but sequences in the 3'-terminal 58 nucleotides were required. RNA3 variants that failed to replicate also failed to transactivate RNA2. These results imply that RNA3 is naturally produced both by transcription from RNA1 and by subsequent RNA1-independent replication and that RNA3 replication may be necessary for transactivation of RNA2

Stroop interference and reverse Stroop interference as potential measures of cognitive ability during exposure to stress

OpenAIRE

景山, 望; 箱田, 裕司; Kageyama, Nozomu; Hakoda, Yuji

2011-01-01

Stroop interference and reverse-Stroop interference are one of the easiest and most powerful effects to demonstrate in a classroom. Therefore, they have been studied not only through basic research in the laboratory but also through applied research in extreme environments. First, we reviewed studies tha investigated Stroop interference and reverse-Stroop interference as hallmark measures of selective at attention and conflict resolution. Second, we reviewed studies that examined the effects ...

Several localized waves induced by linear interference between a nonlinear plane wave and bright solitons

Science.gov (United States)

Qin, Yan-Hong; Zhao, Li-Chen; Yang, Zhan-Ying; Yang, Wen-Li

2018-01-01

We investigate linear interference effects between a nonlinear plane wave and bright solitons, which are admitted by a pair-transition coupled two-component Bose-Einstein condensate. We demonstrate that the interference effects can induce several localized waves possessing distinctive wave structures, mainly including anti-dark solitons, W-shaped solitons, multi-peak solitons, Kuznetsov-Ma like breathers, and multi-peak breathers. Specifically, the explicit conditions for them are clarified by a phase diagram based on the linear interference properties. Furthermore, the interactions between these localized waves are discussed. The detailed analysis indicates that the soliton-soliton interaction induced phase shift brings the collision between these localized waves which can be inelastic for solitons involving collision and can be elastic for breathers. These characters come from the fact that the profile of solitons depends on the relative phase between bright solitons and a plane wave, and the profile of breathers does not depend on the relative phase. These results would motivate more discussions on linear interference between other nonlinear waves. Specifically, the solitons or breathers obtained here are not related to modulational instability. The underlying reasons are discussed in detail. In addition, possibilities to observe these localized waves are discussed in a two species Bose-Einstein condensate.

Single-Word Predictions of Upcoming Language During Comprehension: Evidence from the Cumulative Semantic Interference Task

Science.gov (United States)

Kleinman, Daniel; Runnqvist, Elin; Ferreira, Victor S.

2015-01-01

Comprehenders predict upcoming speech and text on the basis of linguistic input. How many predictions do comprehenders make for an upcoming word? If a listener strongly expects to hear the word “sock”, is the word “shirt” partially expected as well, is it actively inhibited, or is it ignored? The present research addressed these questions by measuring the “downstream” effects of prediction on the processing of subsequently presented stimuli using the cumulative semantic interference paradigm. In three experiments, subjects named pictures (sock) that were presented either in isolation or after strongly constraining sentence frames (“After doing his laundry, Mark always seemed to be missing one…”). Naming sock slowed the subsequent naming of the picture shirt – the standard cumulative semantic interference effect. However, although picture naming was much faster after sentence frames, the interference effect was not modulated by the context (bare vs. sentence) in which either picture was presented. According to the only model of cumulative semantic interference that can account for such a pattern of data, this indicates that comprehenders pre-activated and maintained the pre-activation of best sentence completions (sock) but did not maintain the pre-activation of less likely completions (shirt). Thus, comprehenders predicted only the most probable completion for each sentence. PMID:25917550

Placebo-suggestion modulates conflict resolution in the Stroop Task.

Directory of Open Access Journals (Sweden)

Pedro A Magalhães De Saldanha da Gama

Full Text Available Here, we ask whether placebo-suggestion (without any form of hypnotic induction can modulate the resolution of cognitive conflict. Naïve participants performed a Stroop Task while wearing an EEG cap described as a "brain wave" machine. In Experiment 1, participants were made to believe that the EEG cap would either enhance or decrease their color perception and performance on the Stroop task. In Experiment 2, participants were explicitly asked to imagine that their color perception and performance would be enhanced or decreased (non-hypnotic imaginative suggestion. We observed effects of placebo-suggestion on Stroop interference on accuracy: interference was decreased with positive suggestion and increased with negative suggestion compared to baseline. Intra-individual variability was also increased under negative suggestion compared to baseline. Compliance with the instruction to imagine a modulation of performance, on the other hand, did not influence accuracy and only had a negative impact on response latencies and on intra-individual variability, especially in the congruent condition of the Stroop Task. Taken together, these results demonstrate that expectations induced by a placebo-suggestion can modulate our ability to resolve cognitive conflict, either facilitating or impairing response accuracy depending on the suggestion's contents. Our results also demonstrate a dissociation between placebo-suggestion and non-hypnotic imaginative suggestion.

DNA Replication Control During Drosophila Development: Insights into the Onset of S Phase, Replication Initiation, and Fork Progression

Science.gov (United States)

Hua, Brian L.; Orr-Weaver, Terry L.

2017-01-01

Proper control of DNA replication is critical to ensure genomic integrity during cell proliferation. In addition, differential regulation of the DNA replication program during development can change gene copy number to influence cell size and gene expression. Drosophila melanogaster serves as a powerful organism to study the developmental control of DNA replication in various cell cycle contexts in a variety of differentiated cell and tissue types. Additionally, Drosophila has provided several developmentally regulated replication models to dissect the molecular mechanisms that underlie replication-based copy number changes in the genome, which include differential underreplication and gene amplification. Here, we review key findings and our current understanding of the developmental control of DNA replication in the contexts of the archetypal replication program as well as of underreplication and differential gene amplification. We focus on the use of these latter two replication systems to delineate many of the molecular mechanisms that underlie the developmental control of replication initiation and fork elongation. PMID:28874453

Benefits of a hungry mind: When hungry, exposure to food facilitates proactive interference resolution.

Science.gov (United States)

Maran, Thomas; Sachse, Pierre; Martini, Markus; Furtner, Marco

2017-01-01

Hunger is an everyday motivational state, which biases cognition to detect food. Although evidence exists on how hunger affects basic attentional and mnemonic processes, less is known about how motivational drive for food modulates higher cognition. We aimed to investigate the effects of food deprivation on proactive interference resolution, in the presence and absence of food. Normal-weight participants performed a recency probes paradigm providing an experimental block with food and object stimuli as well as a control block with object stimuli only, in a fasted and a sated state. Results showed that the interaction of shifts in nutritional state with the perception of food cues evoked an altered resolution of proactive interference. Satiety led to impaired performance, whereas a hungry state resulted in strengthened resistance to proactive interference and lying in between, the control block presenting neutral objects remained unaffected by nutritional state manipulation. Additionally, a further increase in proactive interference resolution occurred when the conflicting probe depicted food compared to non-food objects. We conclude that when exposed to food, hunger initiates biased competition of active memory representations in favor of prioritized source information at cost of familiar, but irrelevant information. The implications of these findings are discussed in terms of an arousal-biased competition in working memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

Phase modulated high density collinear holographic data storage system with phase-retrieval reference beam locking and orthogonal reference encoding.

Science.gov (United States)

Liu, Jinpeng; Horimai, Hideyoshi; Lin, Xiao; Huang, Yong; Tan, Xiaodi

2018-02-19

A novel phase modulation method for holographic data storage with phase-retrieval reference beam locking is proposed and incorporated into an amplitude-encoding collinear holographic storage system. Unlike the conventional phase retrieval method, the proposed method locks the data page and the corresponding phase-retrieval interference beam together at the same location with a sequential recording process, which eliminates piezoelectric elements, phase shift arrays and extra interference beams, making the system more compact and phase retrieval easier. To evaluate our proposed phase modulation method, we recorded and then recovered data pages with multilevel phase modulation using two spatial light modulators experimentally. For 4-level, 8-level, and 16-level phase modulation, we achieved the bit error rate (BER) of 0.3%, 1.5% and 6.6% respectively. To further improve data storage density, an orthogonal reference encoding multiplexing method at the same position of medium is also proposed and validated experimentally. We increased the code rate of pure 3/16 amplitude encoding method from 0.5 up to 1.0 and 1.5 using 4-level and 8-level phase modulation respectively.

Aversive emotional interference impacts behavior and prefronto-striatal activity during increasing attentional control.

Science.gov (United States)

Papazacharias, Apostolos; Taurisano, Paolo; Fazio, Leonardo; Gelao, Barbara; Di Giorgio, Annabella; Lo Bianco, Luciana; Quarto, Tiziana; Mancini, Marina; Porcelli, Annamaria; Romano, Raffaella; Caforio, Grazia; Todarello, Orlando; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

2015-01-01

Earlier studies have demonstrated that emotional stimulation modulates attentional processing during goal-directed behavior and related activity of a brain network including the inferior frontal gyrus (IFG) and the caudate nucleus. However, it is not clear how emotional interference modulates behavior and brain physiology during variation in attentional control, a relevant question for everyday life situations in which both emotional stimuli and cognitive load vary. The aim of this study was to investigate the impact of negative emotions on behavior and activity in IFG and caudate nucleus during increasing levels of attentional control. Twenty two healthy subjects underwent event-related functional magnetic resonance imaging while performing a task in which neutral or fearful facial expressions were displayed before stimuli eliciting increasing levels of attentional control processing. Results indicated slower reaction time (RT) and greater right IFG activity when fearful compared with neutral facial expressions preceded the low level of attentional control. On the other hand, fearful facial expressions preceding the intermediate level of attentional control elicited faster behavioral responses and greater activity in the right and left sides of the caudate. Finally, correlation analysis indicated a relationship between behavioral correlates of attentional control after emotional interference and right IFG activity. All together, these results suggest that the impact of negative emotions on attentional processing is differentially elicited at the behavioral and physiological levels as a function of cognitive load.

Inhibitors of Deubiquitinating Enzymes Block HIV-1 Replication and Augment the Presentation of Gag-Derived MHC-I Epitopes.

Science.gov (United States)

Setz, Christian; Friedrich, Melanie; Rauch, Pia; Fraedrich, Kirsten; Matthaei, Alina; Traxdorf, Maximilian; Schubert, Ulrich

2017-08-12

In recent years it has been well established that two major constituent parts of the ubiquitin proteasome system (UPS)-the proteasome holoenzymes and a number of ubiquitin ligases-play a crucial role, not only in virus replication but also in the regulation of the immunogenicity of human immunodeficiency virus type 1 (HIV-1). However, the role in HIV-1 replication of the third major component, the deubiquitinating enzymes (DUBs), has remained largely unknown. In this study, we show that the DUB-inhibitors (DIs) P22077 and PR-619, specific for the DUBs USP7 and USP47, impair Gag processing and thereby reduce the infectivity of released virions without affecting viral protease activity. Furthermore, the replication capacity of X4- and R5-tropic HIV-1 NL4-3 in human lymphatic tissue is decreased upon treatment with these inhibitors without affecting cell viability. Most strikingly, combinatory treatment with DIs and proteasome inhibitors synergistically blocks virus replication at concentrations where mono-treatment was ineffective, indicating that DIs can boost the therapeutic effect of proteasome inhibitors. In addition, P22077 and PR-619 increase the polyubiquitination of Gag and thus its entry into the UPS and the major histocompatibility complex (MHC)-I pathway. In summary, our data point towards a model in which specific inhibitors of DUBs not only interfere with virus spread but also increase the immune recognition of HIV-1 expressing cells.

Achieving nonlinear optical modulation via four-wave mixing in a four-level atomic system

Science.gov (United States)

Li, Hai-Chao; Ge, Guo-Qin; Zubairy, M. Suhail

2018-05-01

We propose an accessible scheme for implementing tunable nonlinear optical amplification and attenuation via a synergetic mechanism of four-wave mixing (FWM) and optical interference in a four-level ladder-type atomic system. By constructing a cyclic atom-field interaction, we show that two reverse FWM processes can coexist via optical transitions in different branches. In the suitable input-field conditions, strong interference effects between the input fields and the generated FWM fields can be induced and result in large amplification and deep attenuation of the output fields. Moreover, such an optical modulation from enhancement to suppression can be controlled by tuning the relative phase. The quantum system can be served as a switchable optical modulator with potential applications in quantum nonlinear optics.

The progression of replication forks at natural replication barriers in live bacteria.

Science.gov (United States)

Moolman, M Charl; Tiruvadi Krishnan, Sriram; Kerssemakers, Jacob W J; de Leeuw, Roy; Lorent, Vincent; Sherratt, David J; Dekker, Nynke H

2016-07-27

Protein-DNA complexes are one of the principal barriers the replisome encounters during replication. One such barrier is the Tus-ter complex, which is a direction dependent barrier for replication fork progression. The details concerning the dynamics of the replisome when encountering these Tus-ter barriers in the cell are poorly understood. By performing quantitative fluorescence microscopy with microfuidics, we investigate the effect on the replisome when encountering these barriers in live Escherichia coli cells. We make use of an E. coli variant that includes only an ectopic origin of replication that is positioned such that one of the two replisomes encounters a Tus-ter barrier before the other replisome. This enables us to single out the effect of encountering a Tus-ter roadblock on an individual replisome. We demonstrate that the replisome remains stably bound after encountering a Tus-ter complex from the non-permissive direction. Furthermore, the replisome is only transiently blocked, and continues replication beyond the barrier. Additionally, we demonstrate that these barriers affect sister chromosome segregation by visualizing specific chromosomal loci in the presence and absence of the Tus protein. These observations demonstrate the resilience of the replication fork to natural barriers and the sensitivity of chromosome alignment to fork progression. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Replication of micro and nano surface geometries

DEFF Research Database (Denmark)

Hansen, Hans Nørgaard; Hocken, R.J.; Tosello, Guido

2011-01-01

The paper describes the state-of-the-art in replication of surface texture and topography at micro and nano scale. The description includes replication of surfaces in polymers, metals and glass. Three different main technological areas enabled by surface replication processes are presented......: manufacture of net-shape micro/nano surfaces, tooling (i.e. master making), and surface quality control (metrology, inspection). Replication processes and methods as well as the metrology of surfaces to determine the degree of replication are presented and classified. Examples from various application areas...... are given including replication for surface texture measurements, surface roughness standards, manufacture of micro and nano structured functional surfaces, replicated surfaces for optical applications (e.g. optical gratings), and process chains based on combinations of repeated surface replication steps....

Study Modules for Calculus-Based General Physics. [Includes Modules 31-34: Inductance; Wave Properties of Light; Interference; and Introduction to Quantum Physics].

Science.gov (United States)

Fuller, Robert G., Ed.; And Others

This is Part of a series of 41 Calculus Based Physics (CBP) modules totaling about 1,000 Pages. The modules include study guides, practice tests, and mastery tests for a full-year individualized courses in calculus-based physics based on the Personalized System of Instruction (PSI). The units are not intended to be used without outside materials;…

A New Replication Norm for Psychology

Directory of Open Access Journals (Sweden)

Etienne P LeBel

2015-10-01

Full Text Available In recent years, there has been a growing concern regarding the replicability of findings in psychology, including a mounting number of prominent findings that have failed to replicate via high-powered independent replication attempts. In the face of this replicability “crisis of confidence”, several initiatives have been implemented to increase the reliability of empirical findings. In the current article, I propose a new replication norm that aims to further boost the dependability of findings in psychology. Paralleling the extant social norm that researchers should peer review about three times as many articles that they themselves publish per year, the new replication norm states that researchers should aim to independently replicate important findings in their own research areas in proportion to the number of original studies they themselves publish per year (e.g., a 4:1 original-to-replication studies ratio. I argue this simple approach could significantly advance our science by increasing the reliability and cumulative nature of our empirical knowledge base, accelerating our theoretical understanding of psychological phenomena, instilling a focus on quality rather than quantity, and by facilitating our transformation toward a research culture where executing and reporting independent direct replications is viewed as an ordinary part of the research process. To help promote the new norm, I delineate (1 how each of the major constituencies of the research process (i.e., funders, journals, professional societies, departments, and individual researchers can incentivize replications and promote the new norm and (2 any obstacles each constituency faces in supporting the new norm.

Communications in interference limited networks

CERN Document Server

2016-01-01

This book offers means to handle interference as a central problem of operating wireless networks. It investigates centralized and decentralized methods to avoid and handle interference as well as approaches that resolve interference constructively. The latter type of approach tries to solve the joint detection and estimation problem of several data streams that share a common medium. In fact, an exciting insight into the operation of networks is that it may be beneficial, in terms of an overall throughput, to actively create and manage interference. Thus, when handled properly, "mixing" of data in networks becomes a useful tool of operation rather than the nuisance as which it has been treated traditionally. With the development of mobile, robust, ubiquitous, reliable and instantaneous communication being a driving and enabling factor of an information centric economy, the understanding, mitigation and exploitation of interference in networks must be seen as a centrally important task.

Wideband Impulse Modulation and Receiver Algorithms for Multiuser Power Line Communications

Directory of Open Access Journals (Sweden)

Andrea M. Tonello

2007-01-01

Full Text Available We consider a bit-interleaved coded wideband impulse-modulated system for power line communications. Impulse modulation is combined with direct-sequence code-division multiple access (DS-CDMA to obtain a form of orthogonal modulation and to multiplex the users. We focus on the receiver signal processing algorithms and derive a maximum likelihood frequency-domain detector that takes into account the presence of impulse noise as well as the intercode interference (ICI and the multiple-access interference (MAI that are generated by the frequency-selective power line channel. To reduce complexity, we propose several simplified frequency-domain receiver algorithms with different complexity and performance. We address the problem of the practical estimation of the channel frequency response as well as the estimation of the correlation of the ICI-MAI-plus-noise that is needed in the detection metric. To improve the estimators performance, a simple hard feedback from the channel decoder is also used. Simulation results show that the scheme provides robust performance as a result of spreading the symbol energy both in frequency (through the wideband pulse and in time (through the spreading code and the bit-interleaved convolutional code.

Joint switched transmit diversity and adaptive modulation in spectrum sharing systems

KAUST Repository

Qaraqe, Khalid A.

2011-01-01

Under the scenario of an underlay cognitive radio network, we propose in this paper an adaptive scheme using switched transmit diversity and adaptive modulation in order to minimize the average number of switched branches at the secondary transmitter while increasing the capacity of the secondary link. The proposed switching efficient scheme (SES) uses the scan and wait (SWC) combining technique where a transmission occurs only when a branch with an acceptable performance is found, otherwise data is buffered. In our scheme, the modulation constellation size and the used transmit branch are determined to achieve the highest spectral efficiency with a minimum processing power, given the fading channel conditions, the required error rate performance, and a peak interference constraint to the primary receiver. Selected numerical examples show that the SES scheme minimizes the average number of switched branches for the average and the high secondary signal-to-noise ratio range. This improvement comes at the expense of a small delay introduced by the SWC technique. For reference, we also compare the performance of the SES scheme to the selection diversity scheme (SDS) where the best branch verifying the modulation mode and the interference constraint is always selected. © 2011 ICST.

Amplitude modulation reflectometer for FTU

International Nuclear Information System (INIS)

Zerbini, M.; Buratti, P.; Centioli, C.; Amadeo, P.

1995-06-01

Amplitude modulation (AM) reflectometry is a modification of the classical frequency sweep technique which allows to perform unambiguous phase delay measurements. An eight-channel AM reflectometer has been realized for the measurement of density profiles on the FTU tokamak in the range. The characteristics of the instrument have been determined in extensive laboratory tests; particular attention has been devoted to the effect of interference with parasitic reflections. The reflectometer is now operating on FTU. Some examples of the first experimental data are discussed

Production of infectious genotype 1b virus particles in cell culture and impairment by replication enhancing mutations.

Directory of Open Access Journals (Sweden)

Thomas Pietschmann

2009-06-01

Full Text Available With the advent of subgenomic hepatitis C virus (HCV replicons, studies of the intracellular steps of the viral replication cycle became possible. These RNAs are capable of self-amplification in cultured human hepatoma cells, but save for the genotype 2a isolate JFH-1, efficient replication of these HCV RNAs requires replication enhancing mutations (REMs, previously also called cell culture adaptive mutations. These mutations cluster primarily in the central region of non-structural protein 5A (NS5A, but may also reside in the NS3 helicase domain or at a distinct position in NS4B. Most efficient replication has been achieved by combining REMs residing in NS3 with distinct REMs located in NS4B or NS5A. However, in spite of efficient replication of HCV genomes containing such mutations, they do not support production of infectious virus particles. By using the genotype 1b isolate Con1, in this study we show that REMs interfere with HCV assembly. Strongest impairment of virus formation was found with REMs located in the NS3 helicase (E1202G and T1280I as well as NS5A (S2204R, whereas a highly adaptive REM in NS4B still allowed virus production although relative levels of core release were also reduced. We also show that cells transfected with the Con1 wild type genome or the genome containing the REM in NS4B release HCV particles that are infectious both in cell culture and in vivo. Our data provide an explanation for the in vitro and in vivo attenuation of cell culture adapted HCV genomes and may open new avenues for the development of fully competent culture systems covering the therapeutically most relevant HCV genotypes.

Centromere replication timing determines different forms of genomic instability in Saccharomyces cerevisiae checkpoint mutants during replication stress.

Science.gov (United States)

Feng, Wenyi; Bachant, Jeff; Collingwood, David; Raghuraman, M K; Brewer, Bonita J

2009-12-01

Yeast replication checkpoint mutants lose viability following transient exposure to hydroxyurea, a replication-impeding drug. In an effort to understand the basis for this lethality, we discovered that different events are responsible for inviability in checkpoint-deficient cells harboring mutations in the mec1 and rad53 genes. By monitoring genomewide replication dynamics of cells exposed to hydroxyurea, we show that cells with a checkpoint deficient allele of RAD53, rad53K227A, fail to duplicate centromeres. Following removal of the drug, however, rad53K227A cells recover substantial DNA replication, including replication through centromeres. Despite this recovery, the rad53K227A mutant fails to achieve biorientation of sister centromeres during recovery from hydroxyurea, leading to secondary activation of the spindle assembly checkpoint (SAC), aneuploidy, and lethal chromosome segregation errors. We demonstrate that cell lethality from this segregation defect could be partially remedied by reinforcing bipolar attachment. In contrast, cells with the mec1-1 sml1-1 mutations suffer from severely impaired replication resumption upon removal of hydroxyurea. mec1-1 sml1-1 cells can, however, duplicate at least some of their centromeres and achieve bipolar attachment, leading to abortive segregation and fragmentation of incompletely replicated chromosomes. Our results highlight the importance of replicating yeast centromeres early and reveal different mechanisms of cell death due to differences in replication fork progression.

Noise-based frequency offset modulation in wideband frequency-selective fading channels

NARCIS (Netherlands)

Meijerink, Arjan; Cotton, S.L.; Bentum, Marinus Jan; Scanlon, W.G.

2009-01-01

A frequency offset modulation scheme using wideband noise carriers is considered. The main advantage of such a scheme is that it enables fast receiver synchronization without channel adaptation, while providing robustness to multipath fading and in-band interference. This is important for low-power

The Approximate Capacity Region of the Symmetric $K$-user Gaussian Interference Channel with Strong Interference

KAUST Repository

Chaaban, Anas

2016-03-01

The symmetric K-user interference channel is studied with the goal of characterizing its capacity region in the strong interference regime within a constant gap. The achievable rate region of a scheme combining rate-splitting at the transmitters and interference alignment and successive decoding/computation at the receivers is derived. Next it is shown that this scheme achieves the so-called greedy-max corner points of the capacity region within a constant gap. By combining this result with previous results by Ordentlich et al. on the sum-capacity of the symmetric interference channel, a constant gap characterization of the capacity region for the strong interference regime is obtained. This leads to the first approximate characterization of the capacity region of the symmetric K-user IC. Furthermore, a new scheme that achieves the sum-capacity of the channel in the strong interference regime within a constant gap is also proposed, and the corresponding gap is calculated. The advantage of the new scheme is that it leads to a characterization within a constant gap without leaving an outage set contrary to the scheme by Ordentlich et al..

The Approximate Capacity Region of the Symmetric $K$-user Gaussian Interference Channel with Strong Interference

KAUST Repository

Chaaban, Anas; Sezgin, Aydin

2016-01-01

The symmetric K-user interference channel is studied with the goal of characterizing its capacity region in the strong interference regime within a constant gap. The achievable rate region of a scheme combining rate-splitting at the transmitters and interference alignment and successive decoding/computation at the receivers is derived. Next it is shown that this scheme achieves the so-called greedy-max corner points of the capacity region within a constant gap. By combining this result with previous results by Ordentlich et al. on the sum-capacity of the symmetric interference channel, a constant gap characterization of the capacity region for the strong interference regime is obtained. This leads to the first approximate characterization of the capacity region of the symmetric K-user IC. Furthermore, a new scheme that achieves the sum-capacity of the channel in the strong interference regime within a constant gap is also proposed, and the corresponding gap is calculated. The advantage of the new scheme is that it leads to a characterization within a constant gap without leaving an outage set contrary to the scheme by Ordentlich et al..

An fMRI Study Dissociating Distance Measures Computed by Broca’s Area in Movement Processing: Clause boundary vs Identity

Directory of Open Access Journals (Sweden)

Andrea eSanti

2015-05-01

Full Text Available Behavioral studies of sentence comprehension suggest that processing long-distance dependencies is subject to interference effects when Noun Phrases (NP similar to the dependency head intervene the dependency. Neuroimaging studies converge in localizing such effects to Broca’s area, showing that activity in Broca’s area increases with the number of NP interveners crossed by a moved NP of the same type. To test if NP interference effects are modulated by adding an intervening clause boundary, which should by hypothesis increase the number of successive-cyclic movements, we conducted an fMRI study contrasting NP interveners with clausal (CP interveners. Our design thus had two components: (I the number of NP interveners crossed by movement was parametrically modulated; (II CP-intervention was contrasted with NP-intervention. The number of NP interveners parametrically modulated a cluster straddling left BA44/45 of Broca’s area, replicating earlier studies. Adding an intervening clause boundary did not significantly modulate the size of the NP interference effect in Broca’s area. Yet, such an interaction effect was observed in the Superior Frontal Gyrus (SFG. Therefore, the involvement of Broca’s area in processing syntactic movement is best captured by memory mechanisms affected by a grammatically instantiated type-identity (ie, NP intervention.

Modulation Classification of Satellite Communication Signals Using Cumulants and Neural Networks

Science.gov (United States)

Smith, Aaron; Evans, Michael; Downey, Joseph

2017-01-01

National Aeronautics and Space Administration (NASA)'s future communication architecture is evaluating cognitive technologies and increased system intelligence. These technologies are expected to reduce the operational complexity of the network, increase science data return, and reduce interference to self and others. In order to increase situational awareness, signal classification algorithms could be applied to identify users and distinguish sources of interference. A significant amount of previous work has been done in the area of automatic signal classification for military and commercial applications. As a preliminary step, we seek to develop a system with the ability to discern signals typically encountered in satellite communication. Proposed is an automatic modulation classifier which utilizes higher order statistics (cumulants) and an estimate of the signal-to-noise ratio. These features are extracted from baseband symbols and then processed by a neural network for classification. The modulation types considered are phase-shift keying (PSK), amplitude and phase-shift keying (APSK),and quadrature amplitude modulation (QAM). Physical layer properties specific to the Digital Video Broadcasting - Satellite- Second Generation (DVB-S2) standard, such as pilots and variable ring ratios, are also considered. This paper will provide simulation results of a candidate modulation classifier, and performance will be evaluated over a range of signal-to-noise ratios, frequency offsets, and nonlinear amplifier distortions.

Pulse-Width-Modulating Driver for Brushless dc Motor

Science.gov (United States)

Salomon, Phil M.

1991-01-01

High-current pulse-width-modulating driver for brushless dc motor features optical coupling of timing signals from low-current control circuitry to high-current motor-driving circuitry. Provides high electrical isolation of motor-power supply, helping to prevent fast, high-current motor-driving pulses from being coupled through power supplies into control circuitry, where they interfere with low-current control signals.

The Inherent Asymmetry of DNA Replication.

Science.gov (United States)

Snedeker, Jonathan; Wooten, Matthew; Chen, Xin

2017-10-06

Semiconservative DNA replication has provided an elegant solution to the fundamental problem of how life is able to proliferate in a way that allows cells, organisms, and populations to survive and replicate many times over. Somewhat lost, however, in our admiration for this mechanism is an appreciation for the asymmetries that occur in the process of DNA replication. As we discuss in this review, these asymmetries arise as a consequence of the structure of the DNA molecule and the enzymatic mechanism of DNA synthesis. Increasing evidence suggests that asymmetries in DNA replication are able to play a central role in the processes of adaptation and evolution by shaping the mutagenic landscape of cells. Additionally, in eukaryotes, recent work has demonstrated that the inherent asymmetries in DNA replication may play an important role in the process of chromatin replication. As chromatin plays an essential role in defining cell identity, asymmetries generated during the process of DNA replication may play critical roles in cell fate decisions related to patterning and development.

Replication dynamics of the yeast genome.

Science.gov (United States)

Raghuraman, M K; Winzeler, E A; Collingwood, D; Hunt, S; Wodicka, L; Conway, A; Lockhart, D J; Davis, R W; Brewer, B J; Fangman, W L

2001-10-05

Oligonucleotide microarrays were used to map the detailed topography of chromosome replication in the budding yeast Saccharomyces cerevisiae. The times of replication of thousands of sites across the genome were determined by hybridizing replicated and unreplicated DNAs, isolated at different times in S phase, to the microarrays. Origin activations take place continuously throughout S phase but with most firings near mid-S phase. Rates of replication fork movement vary greatly from region to region in the genome. The two ends of each of the 16 chromosomes are highly correlated in their times of replication. This microarray approach is readily applicable to other organisms, including humans.

LHCb experience with LFC replication

CERN Document Server

Bonifazi, F; Perez, E D; D'Apice, A; dell'Agnello, L; Düllmann, D; Girone, M; Re, G L; Martelli, B; Peco, G; Ricci, P P; Sapunenko, V; Vagnoni, V; Vitlacil, D

2008-01-01

Database replication is a key topic in the framework of the LHC Computing Grid to allow processing of data in a distributed environment. In particular, the LHCb computing model relies on the LHC File Catalog, i.e. a database which stores information about files spread across the GRID, their logical names and the physical locations of all the replicas. The LHCb computing model requires the LFC to be replicated at Tier-1s. The LCG 3D project deals with the database replication issue and provides a replication service based on Oracle Streams technology. This paper describes the deployment of the LHC File Catalog replication to the INFN National Center for Telematics and Informatics (CNAF) and to other LHCb Tier-1 sites. We performed stress tests designed to evaluate any delay in the propagation of the streams and the scalability of the system. The tests show the robustness of the replica implementation with performance going much beyond the LHCb requirements.

LHCb experience with LFC replication

International Nuclear Information System (INIS)

Bonifazi, F; Carbone, A; D'Apice, A; Dell'Agnello, L; Re, G L; Martelli, B; Ricci, P P; Sapunenko, V; Vitlacil, D; Perez, E D; Duellmann, D; Girone, M; Peco, G; Vagnoni, V

2008-01-01

Database replication is a key topic in the framework of the LHC Computing Grid to allow processing of data in a distributed environment. In particular, the LHCb computing model relies on the LHC File Catalog, i.e. a database which stores information about files spread across the GRID, their logical names and the physical locations of all the replicas. The LHCb computing model requires the LFC to be replicated at Tier-1s. The LCG 3D project deals with the database replication issue and provides a replication service based on Oracle Streams technology. This paper describes the deployment of the LHC File Catalog replication to the INFN National Center for Telematics and Informatics (CNAF) and to other LHCb Tier-1 sites. We performed stress tests designed to evaluate any delay in the propagation of the streams and the scalability of the system. The tests show the robustness of the replica implementation with performance going much beyond the LHCb requirements

Auditory and motor imagery modulate learning in music performance.

Science.gov (United States)

Brown, Rachel M; Palmer, Caroline

2013-01-01

Skilled performers such as athletes or musicians can improve their performance by imagining the actions or sensory outcomes associated with their skill. Performers vary widely in their auditory and motor imagery abilities, and these individual differences influence sensorimotor learning. It is unknown whether imagery abilities influence both memory encoding and retrieval. We examined how auditory and motor imagery abilities influence musicians' encoding (during Learning, as they practiced novel melodies), and retrieval (during Recall of those melodies). Pianists learned melodies by listening without performing (auditory learning) or performing without sound (motor learning); following Learning, pianists performed the melodies from memory with auditory feedback (Recall). During either Learning (Experiment 1) or Recall (Experiment 2), pianists experienced either auditory interference, motor interference, or no interference. Pitch accuracy (percentage of correct pitches produced) and temporal regularity (variability of quarter-note interonset intervals) were measured at Recall. Independent tests measured auditory and motor imagery skills. Pianists' pitch accuracy was higher following auditory learning than following motor learning and lower in motor interference conditions (Experiments 1 and 2). Both auditory and motor imagery skills improved pitch accuracy overall. Auditory imagery skills modulated pitch accuracy encoding (Experiment 1): Higher auditory imagery skill corresponded to higher pitch accuracy following auditory learning with auditory or motor interference, and following motor learning with motor or no interference. These findings suggest that auditory imagery abilities decrease vulnerability to interference and compensate for missing auditory feedback at encoding. Auditory imagery skills also influenced temporal regularity at retrieval (Experiment 2): Higher auditory imagery skill predicted greater temporal regularity during Recall in the presence of

Auditory and motor imagery modulate learning in music performance

Science.gov (United States)

Brown, Rachel M.; Palmer, Caroline

2013-01-01

Skilled performers such as athletes or musicians can improve their performance by imagining the actions or sensory outcomes associated with their skill. Performers vary widely in their auditory and motor imagery abilities, and these individual differences influence sensorimotor learning. It is unknown whether imagery abilities influence both memory encoding and retrieval. We examined how auditory and motor imagery abilities influence musicians' encoding (during Learning, as they practiced novel melodies), and retrieval (during Recall of those melodies). Pianists learned melodies by listening without performing (auditory learning) or performing without sound (motor learning); following Learning, pianists performed the melodies from memory with auditory feedback (Recall). During either Learning (Experiment 1) or Recall (Experiment 2), pianists experienced either auditory interference, motor interference, or no interference. Pitch accuracy (percentage of correct pitches produced) and temporal regularity (variability of quarter-note interonset intervals) were measured at Recall. Independent tests measured auditory and motor imagery skills. Pianists' pitch accuracy was higher following auditory learning than following motor learning and lower in motor interference conditions (Experiments 1 and 2). Both auditory and motor imagery skills improved pitch accuracy overall. Auditory imagery skills modulated pitch accuracy encoding (Experiment 1): Higher auditory imagery skill corresponded to higher pitch accuracy following auditory learning with auditory or motor interference, and following motor learning with motor or no interference. These findings suggest that auditory imagery abilities decrease vulnerability to interference and compensate for missing auditory feedback at encoding. Auditory imagery skills also influenced temporal regularity at retrieval (Experiment 2): Higher auditory imagery skill predicted greater temporal regularity during Recall in the presence of

Interference-exact radiative transfer equation

DEFF Research Database (Denmark)

Partanen, Mikko; Haÿrynen, Teppo; Oksanen, Jani

2017-01-01

Maxwell's equations with stochastic or quantum optical source terms accounting for the quantum nature of light. We show that both the nonlocal wave and local particle features associated with interference and emission of propagating fields in stratified geometries can be fully captured by local damping...... and scattering coefficients derived from the recently introduced quantized fluctuational electrodynamics (QFED) framework. In addition to describing the nonlocal optical interference processes as local directionally resolved effects, this allows reformulating the well known and widely used radiative transfer...... equation (RTE) as a physically transparent interference-exact model that extends the useful range of computationally efficient and quantum optically accurate interference-aware optical models from simple structures to full optical devices....

High-Resolution Replication Profiles Define the Stochastic Nature of Genome Replication Initiation and Termination

Directory of Open Access Journals (Sweden)

Michelle Hawkins

2013-11-01

Full Text Available Eukaryotic genome replication is stochastic, and each cell uses a different cohort of replication origins. We demonstrate that interpreting high-resolution Saccharomyces cerevisiae genome replication data with a mathematical model allows quantification of the stochastic nature of genome replication, including the efficiency of each origin and the distribution of termination events. Single-cell measurements support the inferred values for stochastic origin activation time. A strain, in which three origins were inactivated, confirmed that the distribution of termination events is primarily dictated by the stochastic activation time of origins. Cell-to-cell variability in origin activity ensures that termination events are widely distributed across virtually the whole genome. We propose that the heterogeneity in origin usage contributes to genome stability by limiting potentially deleterious events from accumulating at particular loci.

Interference-Aware Spectrum Sharing Techniques for Next Generation Wireless Networks

KAUST Repository

Qaraqe, Marwa Khalid

2011-11-20

Background: Reliable high-speed data communication that supports multimedia application for both indoor and outdoor mobile users is a fundamental requirement for next generation wireless networks and requires a dense deployment of physically coexisting network architectures. Due to the limited spectrum availability, a novel interference-aware spectrum-sharing concept is introduced where networks that suffer from congested spectrums (secondary-networks) are allowed to share the spectrum with other networks with available spectrum (primary-networks) under the condition that limited interference occurs to primary networks. Objective: Multiple-antenna and adaptive rate can be utilized as a power-efficient technique for improving the data rate of the secondary link while satisfying the interference constraint of the primary link by allowing the secondary user to adapt its transmitting antenna, power, and rate according to the channel state information. Methods: Two adaptive schemes are proposed using multiple-antenna transmit diversity and adaptive modulation in order to increase the spectral-efficiency of the secondary link while maintaining minimum interference with the primary. Both the switching efficient scheme (SES) and bandwidth efficient scheme (BES) use the scan-and-wait combining antenna technique (SWC) where there is a secondary transmission only when a branch with an acceptable performance is found; else the data is buffered. Results: In both these schemes the constellation size and selected transmit branch are determined to minimized the average number of switches and achieve the highest spectral efficiency given a minimum bit-error-rate (BER), fading conditions, and peak interference constraint. For delayed sensitive applications, two schemes using power control are used: SES-PC and BES-PC. In these schemes the secondary transmitter sends data using a nominal power level, which is optimized to minimize the average delay. Several numerical examples show

DNA replication and post-replication repair in U.V.-sensitive mouse neuroblastoma cells

International Nuclear Information System (INIS)

Lavin, M.F.; McCombe, P.; Kidson, C.

1976-01-01

Mouse neuroblastoma cells differentiated when grown in the absence of serum; differentiation was reversed on the addition of serum. Differentiated cells were more sensitive to U.V.-radiation than proliferating cells. Whereas addition of serum to differentiated neuroblastoma cells normally resulted in immediate, synchronous entry into S phase, irradiation just before the addition of serum resulted in a long delay in the onset of DNA replication. During this lag period, incorporated 3 H-thymidine appeared in the light density region of CsCl gradients, reflecting either repair synthesis or abortive replication. Post-replication repair (gap-filling) was found to be present in proliferating cells and at certain times in differentiated cells. It is suggested that the sensitivity of differentiated neuroblastoma cells to U.V.-radiation may have been due to ineffective post-replication repair or to deficiencies in more than one repair mechanism, with reduction in repair capacity beyond a critical threshold. (author)

Laser self-mixing interference fibre sensor

International Nuclear Information System (INIS)

Zhu Jun; Zhao Yan; Jin Guofan

2008-01-01

Fibre sensors exhibit a number of advantages over other sensors such as high sensitivity, electric insulation, corrosion resistance, interference rejection and so on. And laser self-mixing interference can accurately detect the phase difference of feedback light. In this paper, a novel laser self-mixing interference fibre sensor that combines the advantages of fibre sensors with those of laser self-mixing interference is presented. Experimental configurations are set up to study the relationship between laser power output and phase of laser feedback light when the fibre trembles or when the fibre is stretched or pressed. The theoretical analysis of pressure sensors based on laser self-mixing interference is indicated to accord with the experimental results. (classical areas of phenomenology)

47 CFR 27.1221 - Interference protection.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Interference protection. 27.1221 Section 27... Technical Standards § 27.1221 Interference protection. (a) Interference protection will be afforded to BRS... height benchmark (hbm). (c) Protection for Receiving Antennas not Exceeding the Height Benchmark. Absent...

Binaural Interference: Quo Vadis?

Science.gov (United States)

Jerger, James; Silman, Shlomo; Silverman, Carol; Emmer, Michele

2017-04-01

The reality of the phenomenon of binaural interference with speech recognition has been debated for two decades. Research has taken one of two avenues; group studies or case reports. In group studies, a sample of the elderly population is tested on speech recognition under three conditions; binaural, monaural right and monaural left. The aim is to determine the percent of the sample in which the expected outcome (binaural score-better-than-either-monaural score) is reversed (i.e., one of the monaural scores is better than the binaural score). This outcome has been commonly used to define binaural interference. The object of group studies is to answer the "how many" question, what is the prevalence of binaural interference in the sample. In case reports the binaural interference conclusion suggested by the speech recognition tests is not accepted until it has been corroborated by other independent diagnostic audiological measures. The aim is to attempt to determine the basis for the findings, to answer the "why" question. This article is at once tutorial, editorial and a case report. We argue that it is time to accept the reality of the phenomenon of binaural interference, to eschew group statistical approaches in search of an answer to the "how many" question, and to focus on individual case reports in search of an answer to the "why" question. American Academy of Audiology.

DATABASE REPLICATION IN HETEROGENOUS PLATFORM

OpenAIRE

Hendro Nindito; Evaristus Didik Madyatmadja; Albert Verasius Dian Sano

2014-01-01

The application of diverse database technologies in enterprises today is increasingly a common practice. To provide high availability and survavibality of real-time information, a database replication technology that has capability to replicate databases under heterogenous platforms is required. The purpose of this research is to find the technology with such capability. In this research, the data source is stored in MSSQL database server running on Windows. The data will be replicated to MyS...

A SELEX-screened aptamer of human hepatitis B virus RNA encapsidation signal suppresses viral replication.

Directory of Open Access Journals (Sweden)

Hui Feng

Full Text Available BACKGROUND: The specific interaction between hepatitis B virus (HBV polymerase (P protein and the ε RNA stem-loop on pregenomic (pg RNA is crucial for viral replication. It triggers both pgRNA packaging and reverse transcription and thus represents an attractive antiviral target. RNA decoys mimicking ε in P protein binding but not supporting replication might represent novel HBV inhibitors. However, because generation of recombinant enzymatically active HBV polymerase is notoriously difficult, such decoys have as yet not been identified. METHODOLOGY/PRINCIPAL FINDINGS: Here we used a SELEX approach, based on a new in vitro reconstitution system exploiting a recombinant truncated HBV P protein (miniP, to identify potential ε decoys in two large ε RNA pools with randomized upper stem. Selection of strongly P protein binding RNAs correlated with an unexpected strong enrichment of A residues. Two aptamers, S6 and S9, displayed particularly high affinity and specificity for miniP in vitro, yet did not support viral replication when part of a complete HBV genome. Introducing S9 RNA into transiently HBV producing HepG2 cells strongly suppressed pgRNA packaging and DNA synthesis, indicating the S9 RNA can indeed act as an ε decoy that competitively inhibits P protein binding to the authentic ε signal on pgRNA. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the first successful identification of human HBV ε aptamers by an in vitro SELEX approach. Effective suppression of HBV replication by the S9 aptamer provides proof-of-principle for the ability of ε decoy RNAs to interfere with viral P-ε complex formation and suggests that S9-like RNAs may further be developed into useful therapeutics against chronic hepatitis B.

Exploiting replicative stress to treat cancer

DEFF Research Database (Denmark)

Dobbelstein, Matthias; Sørensen, Claus Storgaard

2015-01-01

DNA replication in cancer cells is accompanied by stalling and collapse of the replication fork and signalling in response to DNA damage and/or premature mitosis; these processes are collectively known as 'replicative stress'. Progress is being made to increase our understanding of the mechanisms...

An accumulator model of semantic interference

NARCIS (Netherlands)

van Maanen, Leendert; van Rijn, Hedderik

To explain latency effects in picture-word interference tasks, cognitive models need to account for both interference and stimulus onset asynchrony (SOA) effects. As opposed to most models of picture-word interference, which model the time course during the task in a ballistic manner, the RACE model

Double-stranded RNA interferes in a sequence-specific manner with the infection of representative members of the two viroid families

International Nuclear Information System (INIS)

Carbonell, Alberto; Martinez de Alba, Angel-Emilio; Flores, Ricardo; Gago, Selma

2008-01-01

Infection by viroids, non-protein-coding circular RNAs, occurs with the accumulation of 21-24 nt viroid-derived small RNAs (vd-sRNAs) with characteristic properties of small interfering RNAs (siRNAs) associated to RNA silencing. The vd-sRNAs most likely derive from dicer-like (DCL) enzymes acting on viroid-specific dsRNA, the key elicitor of RNA silencing, or on the highly structured genomic RNA. Previously, viral dsRNAs delivered mechanically or agroinoculated have been shown to interfere with virus infection in a sequence-specific manner. Here, we report similar results with members of the two families of nuclear- and chloroplast-replicating viroids. Moreover, homologous vd-sRNAs co-delivered mechanically also interfered with one of the viroids examined. The interference was sequence-specific, temperature-dependent and, in some cases, also dependent on the dose of the co-inoculated dsRNA or vd-sRNAs. The sequence-specific nature of these effects suggests the involvement of the RNA induced silencing complex (RISC), which provides sequence specificity to RNA silencing machinery. Therefore, viroid titer in natural infections might be regulated by the concerted action of DCL and RISC. Viroids could have evolved their secondary structure as a compromise between resistance to DCL and RISC, which act preferentially against RNAs with compact and relaxed secondary structures, respectively. In addition, compartmentation, association with proteins or active replication might also help viroids to elude their host RNA silencing machinery

(Sub-)Optimality of Treating Interference as Noise in the Cellular Uplink With Weak Interference

KAUST Repository

Gherekhloo, Soheil; Chaaban, Anas; Di, Chen; Sezgin, Aydin

2015-01-01

Despite the simplicity of the scheme of treating interference as noise (TIN), it was shown to be sum-capacity optimal in the Gaussian interference channel (IC) with very-weak (noisy) interference. In this paper, the two-user IC is altered by introducing an additional transmitter that wants to communicate with one of the receivers of the IC. The resulting network thus consists of a point-to-point channel interfering with a multiple access channel (MAC) and is denoted by PIMAC. The sum-capacity of the PIMAC is studied with main focus on the optimality of TIN. It turns out that TIN in its naive variant, where all transmitters are active and both receivers use TIN for decoding, is not the best choice for the PIMAC. In fact, a scheme that combines both time division multiple access and TIN (TDMA-TIN) strictly outperforms the naive-TIN scheme. Furthermore, it is shown that in some regimes, TDMA-TIN achieves the sum-capacity for the deterministic PIMAC and the sum-capacity within a constant gap for the Gaussian PIMAC. In addition, it is shown that, even for very-weak interference, there are some regimes where a combination of interference alignment with power control and TIN at the receiver side outperforms TDMA-TIN. As a consequence, on the one hand, TIN in a cellular uplink is approximately optimal in certain regimes. On the other hand, those regimes cannot be simply described by the strength of interference.

(Sub-)Optimality of Treating Interference as Noise in the Cellular Uplink With Weak Interference

KAUST Repository

Gherekhloo, Soheil

2015-11-09

Despite the simplicity of the scheme of treating interference as noise (TIN), it was shown to be sum-capacity optimal in the Gaussian interference channel (IC) with very-weak (noisy) interference. In this paper, the two-user IC is altered by introducing an additional transmitter that wants to communicate with one of the receivers of the IC. The resulting network thus consists of a point-to-point channel interfering with a multiple access channel (MAC) and is denoted by PIMAC. The sum-capacity of the PIMAC is studied with main focus on the optimality of TIN. It turns out that TIN in its naive variant, where all transmitters are active and both receivers use TIN for decoding, is not the best choice for the PIMAC. In fact, a scheme that combines both time division multiple access and TIN (TDMA-TIN) strictly outperforms the naive-TIN scheme. Furthermore, it is shown that in some regimes, TDMA-TIN achieves the sum-capacity for the deterministic PIMAC and the sum-capacity within a constant gap for the Gaussian PIMAC. In addition, it is shown that, even for very-weak interference, there are some regimes where a combination of interference alignment with power control and TIN at the receiver side outperforms TDMA-TIN. As a consequence, on the one hand, TIN in a cellular uplink is approximately optimal in certain regimes. On the other hand, those regimes cannot be simply described by the strength of interference.

Neural Network-Based Receiver in Band-Limited Communication System with MPPSK Modulation

Directory of Open Access Journals (Sweden)

Wang Zixin

2018-01-01

Full Text Available As a type of the spectrally efficient modulation, the m-ary phase position shift keying (MPPSK has been considered to meet the increasing spectrum requirement in the future wireless system. To limit the signal bandwidth and cancel the out-band interference the band-pass filters are used, which introduce the waveform distortion and inter-symbol interference (ISI. Therefore, a single hidden-layer neural network (NN-based receiver is proposed to jointly equalize and demodulate the received signal. The impulse response of the system is static and the network parameters can be obtained after off-line training. The number of the hidden nodes is also determined through simulations. Simulation results show that the NN-based receiver works well in the communication system with different allocated bandwidths. By observing the modified confusion matrix, the false symbol decision is relevant to modulation index, waveform distortions and the ISI.

Adoption of the B2SAFE EUDAT replication service by the EPOS community

Science.gov (United States)

Cacciari, Claudio; Fares, Massimo; Fiameni, Giuseppe; Michelini, Alberto; Danecek, Peter; Wittenburg, Peter

2014-05-01

B2SAFE is the EUDAT service for moving and replicating data between sites and storage systems for different purposes. The goal of B2SAFE is to keep the data from a repository safe by replicating it across different geographical and administrative zones according to a set of well-defined policies. It is also a way to store large volumes of data permanently at those sites which are providing powerful on-demand data analysis facilities. In particular, B2SAFE operates on the domain of registered data where data objects are referable via persistent identifiers (PIDs). B2SAFE is more than just copying data because the PIDs must be carefully managed when data objects are moved or replicated. The EUDAT B2SAFE Service offers functionality to replicate datasets across different data centres in a safe and efficient way while maintaining all information required to easily find and query information about the replica locations. The information about the replica locations and other important information is stored in PID records, each managed in separate administrative domains. The B2SAFE Service is implemented as an iRODS module providing a set of iRODS rules or policies to interface with the EPIC handle API and uses the iRODS middleware to replicate datasets from a source data (or community) centre to a destination data centre. The definition of the dataset(s) to replicate is flexible and up to the communities using the B2SAFE service. While the B2SAFE is internally using the EPIC handle API, communities have the choice to use any PID system they prefer to assign PIDs to their digital objects. A reference to one or more EUDAT B2SAFE PIDs is returned by the B2SAFE service when a dataset is replicated. The presentation will introduce the problem space of B2SAFE, presents the achievements that have been made during the last year for enabling communities to make use of the B2SAFE service, demonstrates a EPOS use cases, outlines the commonalities and differences between the policies

Chromatin maturation depends on continued DNA-replication

International Nuclear Information System (INIS)

Schlaeger, E.J.; Puelm, W.; Knippers, R.

1983-01-01

The structure of [ 3 H]thymidine pulse-labeled chromatin in lymphocytes differs from that of non-replicating chromatin by several operational criteria which are related to the higher nuclease sensitivity of replicating chromatin. These structural features of replicating chromatin rapidly disappear when the [ 3 H]thymidine pulse is followed by a chase in the presence of an excess of non-radioactive thymidine. However, when the rate of DNA replication is reduced, as in cycloheximide-treated lymphocytes, chromatin maturation is retarded. No chromatin maturation is observed when nuclei from pulse-labeled lymphocytes are incubated in vitro in the absence of DNA precursors. In contrast, when these nuclei are incubated under conditions known to be optimal for DNA replication, the structure of replicating chromatin is efficiently converted to that of 'mature', non-replicating chromatin. The authors conclude that the properties of nascent DNA and/or the distance from the replication fork are important factors in chromatin maturation. (Auth.)

The Escherichia coli Tus-Ter replication fork barrier causes site-specific DNA replication perturbation in yeast

DEFF Research Database (Denmark)

Larsen, Nicolai B; Sass, Ehud; Suski, Catherine

2014-01-01

Replication fork (RF) pausing occurs at both 'programmed' sites and non-physiological barriers (for example, DNA adducts). Programmed RF pausing is required for site-specific DNA replication termination in Escherichia coli, and this process requires the binding of the polar terminator protein, Tus...... as a versatile, site-specific, heterologous DNA replication-perturbing system, with a variety of potential applications....

Consolidation through the looking-glass: sleep-dependent proactive interference on visuomotor adaptation in children.

Science.gov (United States)

Urbain, Charline; Houyoux, Emeline; Albouy, Geneviève; Peigneux, Philippe

2014-02-01

Although a beneficial role of post-training sleep for declarative memory has been consistently evidenced in children, as in adults, available data suggest that procedural memory consolidation does not benefit from sleep in children. However, besides the absence of performance gains in children, sleep-dependent plasticity processes involved in procedural memory consolidation might be expressed through differential interference effects on the learning of novel but related procedural material. To test this hypothesis, 32 10-12-year-old children were trained on a motor rotation adaptation task. After either a sleep or a wake period, they were first retested on the same rotation applied at learning, thus assessing offline sleep-dependent changes in performance, then on the opposite (unlearned) rotation to assess sleep-dependent modulations in proactive interference coming from the consolidated visuomotor memory trace. Results show that children gradually improve performance over the learning session, showing effective adaptation to the imposed rotation. In line with previous findings, no sleep-dependent changes in performance were observed for the learned rotation. However, presentation of the opposite, unlearned deviation elicited significantly higher interference effects after post-training sleep than wakefulness in children. Considering that a definite feature of procedural motor memory and skill acquisition is the implementation of highly automatized motor behaviour, thus lacking flexibility, our results suggest a better integration and/or automation or motor adaptation skills after post-training sleep, eventually resulting in higher proactive interference effects on untrained material. © 2013 European Sleep Research Society.

Enzymatic recognition of DNA replication origins

International Nuclear Information System (INIS)

Stayton, M.M.; Bertsch, L.; Biswas, S.

1983-01-01

In this paper we discuss the process of recognition of the complementary-strand origin with emphasis on RNA polymerase action in priming M13 DNA replication, the role of primase in G4 DNA replication, and the function of protein n, a priming protein, during primosome assembly. These phage systems do not require several of the bacterial DNA replication enzymes, particularly those involved in the regulation of chromosome copy number of the initiatiion of replication of duplex DNA. 51 references, 13 figures, 1 table

An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies.

Science.gov (United States)

Komatsu, Tetsuro; Nagata, Kyosuke; Wodrich, Harald

2016-02-01

Promyelocytic leukemia protein nuclear bodies (PML-NBs) are subnuclear domains implicated in cellular antiviral responses. Despite the antiviral activity, several nuclear replicating DNA viruses use the domains as deposition sites for the incoming viral genomes and/or as sites for viral DNA replication, suggesting that PML-NBs are functionally relevant during early viral infection to establish productive replication. Although PML-NBs and their components have also been implicated in the adenoviral life cycle, it remains unclear whether incoming adenoviral genome complexes target PML-NBs. Here we show using immunofluorescence and live-cell imaging analyses that incoming adenovirus genome complexes neither localize at nor recruit components of PML-NBs during early phases of infection. We further show that the viral DNA binding protein (DBP), an early expressed viral gene and essential DNA replication factor, independently targets PML-NBs. We show that DBP oligomerization is required to selectively recruit the PML-NB components Sp100 and USP7. Depletion experiments suggest that the absence of one PML-NB component might not affect the recruitment of other components toward DBP oligomers. Thus, our findings suggest a model in which an adenoviral DNA replication factor, but not incoming viral genome complexes, targets and modulates PML-NBs to support a conducive state for viral DNA replication and argue against a generalized concept that PML-NBs target incoming viral genomes. The immediate fate upon nuclear delivery of genomes of incoming DNA viruses is largely unclear. Early reports suggested that incoming genomes of herpesviruses are targeted and repressed by PML-NBs immediately upon nuclear import. Genome localization and/or viral DNA replication has also been observed at PML-NBs for other DNA viruses. Thus, it was suggested that PML-NBs may immediately sense and target nuclear viral genomes and hence serve as sites for deposition of incoming viral genomes and

Surface Microstructure Replication in Injection Moulding

DEFF Research Database (Denmark)

Hansen, Hans Nørgaard; Arlø, Uffe Rolf

2005-01-01

topography is transcribed onto the plastic part through complex mechanisms. This replication however, is not perfect, and the replication quality depends on the plastic material properties, the topography itself, and the process conditions. This paper describes and discusses an investigation of injection...... moulding of surface microstructures. Emphasis is put on the ability to replicate surface microstructures under normal injection moulding conditions, notably with low cost materials at low mould temperatures. The replication of surface microstructures in injection moulding has been explored...... for Polypropylene at low mould temperatures. The process conditions were varied over the recommended process window for the material. The geometry of the obtained structures was analyzed. Evidence suggests that step height replication quality depends linearly on structure width in a certain range. Further...

Face age modulates gaze following in young adults.

Science.gov (United States)

Ciardo, Francesca; Marino, Barbara F M; Actis-Grosso, Rossana; Rossetti, Angela; Ricciardelli, Paola

2014-04-22

Gaze-following behaviour is considered crucial for social interactions which are influenced by social similarity. We investigated whether the degree of similarity, as indicated by the perceived age of another person, can modulate gaze following. Participants of three different age-groups (18-25; 35-45; over 65) performed an eye movement (a saccade) towards an instructed target while ignoring the gaze-shift of distracters of different age-ranges (6-10; 18-25; 35-45; over 70). The results show that gaze following was modulated by the distracter face age only for young adults. Particularly, the over 70 year-old distracters exerted the least interference effect. The distracters of a similar age-range as the young adults (18-25; 35-45) had the most effect, indicating a blurred own-age bias (OAB) only for the young age group. These findings suggest that face age can modulate gaze following, but this modulation could be due to factors other than just OAB (e.g., familiarity).

Spermine attenuates the action of the DNA intercalator, actinomycin D, on DNA binding and the inhibition of transcription and DNA replication.

Science.gov (United States)

Wang, Sheng-Yu; Lee, Alan Yueh-Luen; Lee, Yueh-Luen; Lai, Yi-Hua; Chen, Jeremy J W; Wu, Wen-Lin; Yuann, Jeu-Ming P; Su, Wang-Lin; Chuang, Show-Mei; Hou, Ming-Hon

2012-01-01

The anticancer activity of DNA intercalators is related to their ability to intercalate into the DNA duplex with high affinity, thereby interfering with DNA replication and transcription. Polyamines (spermine in particular) are almost exclusively bound to nucleic acids and are involved in many cellular processes that require nucleic acids. Until now, the effects of polyamines on DNA intercalator activities have remained unclear because intercalation is the most important mechanism employed by DNA-binding drugs. Herein, using actinomycin D (ACTD) as a model, we have attempted to elucidate the effects of spermine on the action of ACTD, including its DNA-binding ability, RNA and DNA polymerase interference, and its role in the transcription and replication inhibition of ACTD within cells. We found that spermine interfered with the binding and stabilization of ACTD to DNA. The presence of increasing concentrations of spermine enhanced the transcriptional and replication activities of RNA and DNA polymerases, respectively, in vitro treated with ActD. Moreover, a decrease in intracellular polyamine concentrations stimulated by methylglyoxal-bis(guanylhydrazone) (MGBG) enhanced the ACTD-induced inhibition of c-myc transcription and DNA replication in several cancer cell lines. The results indicated that spermine attenuates ACTD binding to DNA and its inhibition of transcription and DNA replication both in vitro and within cells. Finally, a synergistic antiproliferative effect of MGBG and ACTD was observed in a cell viability assay. Our findings will be of significant relevance to future developments in combination with cancer therapy by enhancing the anticancer activity of DNA interactors through polyamine depletion.

Spermine attenuates the action of the DNA intercalator, actinomycin D, on DNA binding and the inhibition of transcription and DNA replication.

Directory of Open Access Journals (Sweden)

Sheng-Yu Wang

Full Text Available The anticancer activity of DNA intercalators is related to their ability to intercalate into the DNA duplex with high affinity, thereby interfering with DNA replication and transcription. Polyamines (spermine in particular are almost exclusively bound to nucleic acids and are involved in many cellular processes that require nucleic acids. Until now, the effects of polyamines on DNA intercalator activities have remained unclear because intercalation is the most important mechanism employed by DNA-binding drugs. Herein, using actinomycin D (ACTD as a model, we have attempted to elucidate the effects of spermine on the action of ACTD, including its DNA-binding ability, RNA and DNA polymerase interference, and its role in the transcription and replication inhibition of ACTD within cells. We found that spermine interfered with the binding and stabilization of ACTD to DNA. The presence of increasing concentrations of spermine enhanced the transcriptional and replication activities of RNA and DNA polymerases, respectively, in vitro treated with ActD. Moreover, a decrease in intracellular polyamine concentrations stimulated by methylglyoxal-bis(guanylhydrazone (MGBG enhanced the ACTD-induced inhibition of c-myc transcription and DNA replication in several cancer cell lines. The results indicated that spermine attenuates ACTD binding to DNA and its inhibition of transcription and DNA replication both in vitro and within cells. Finally, a synergistic antiproliferative effect of MGBG and ACTD was observed in a cell viability assay. Our findings will be of significant relevance to future developments in combination with cancer therapy by enhancing the anticancer activity of DNA interactors through polyamine depletion.

Replication Protein A (RPA) Phosphorylation Prevents RPA Association with Replication Centers

OpenAIRE

Vassin, Vitaly M.; Wold, Marc S.; Borowiec, James A.

2004-01-01

Mammalian replication protein A (RPA) undergoes DNA damage-dependent phosphorylation at numerous sites on the N terminus of the RPA2 subunit. To understand the functional significance of RPA phosphorylation, we expressed RPA2 variants in which the phosphorylation sites were converted to aspartate (RPA2D) or alanine (RPA2A). Although RPA2D was incorporated into RPA heterotrimers and supported simian virus 40 DNA replication in vitro, the RPA2D mutant was selectively unable to associate with re...

Filling Predictable and Unpredictable Gaps, with and without Similarity-Based Interference: Evidence for LIFG Effects of Dependency Processing.

Science.gov (United States)

Leiken, Kimberly; McElree, Brian; Pylkkänen, Liina

2015-01-01

One of the most replicated findings in neurolinguistic literature on syntax is the increase of hemodynamic activity in the left inferior frontal gyrus (LIFG) in response to object relative (OR) clauses compared to subject relative clauses. However, behavioral studies have shown that ORs are primarily only costly when similarity-based interference is involved and recently, Leiken and Pylkkänen (2014) showed with magnetoencephalography (MEG) that an LIFG increase at an OR gap is also dependent on such interference. However, since ORs always involve a cue indicating an upcoming dependency formation, OR dependencies could be processed already prior to the gap-site and thus show no sheer dependency effects at the gap itself. To investigate the role of gap predictability in LIFG dependency effects, this MEG study compared ORs to verb phrase ellipsis (VPE), which was used as an example of a non-predictable dependency. Additionally, we explored LIFG sensitivity to filler-gap order by including right node raising structures, in which the order of filler and gap is reverse to that of ORs and VPE. Half of the stimuli invoked similarity-based interference and half did not. Our results demonstrate that LIFG effects of dependency can be elicited regardless of whether the dependency is predictable, the stimulus materials evoke similarity-based interference, or the filler precedes the gap. Thus, contrary to our own prior data, the current findings suggest a highly general role for the LIFG in dependency interpretation that is not limited to environments involving similarity-based interference. Additionally, the millisecond time-resolution of MEG allowed for a detailed characterization of the temporal profiles of LIFG dependency effects across our three constructions, revealing that the timing of these effects is somewhat construction-specific.

Variance Swap Replication: Discrete or Continuous?

Directory of Open Access Journals (Sweden)

Fabien Le Floc’h

2018-02-01

Full Text Available The popular replication formula to price variance swaps assumes continuity of traded option strikes. In practice, however, there is only a discrete set of option strikes traded on the market. We present here different discrete replication strategies and explain why the continuous replication price is more relevant.

Optical interference with noncoherent states

International Nuclear Information System (INIS)

Sagi, Yoav; Firstenberg, Ofer; Fisher, Amnon; Ron, Amiram

2003-01-01

We examine a typical two-source optical interference apparatus consisting of two cavities, a beam splitter, and two detectors. We show that field-field interference occurs even when the cavities are not initially in coherent states but rather in other nonclassical states. However, we find that the visibility of the second-order interference, that is, the expectation values of the detectors' readings, changes from 100%, when the cavities are prepared in coherent states, to zero visibility when they are initially in single Fock states. We calculate the fourth-order interference, and for the latter case find that it corresponds to a case where the currents oscillate with 100% visibility, but with a random phase for every experiment. Finally, we suggest an experimental realization of the apparatus with nonclassical sources

Interference management using direct sequence spread spectrum ...

African Journals Online (AJOL)

Interference management using direct sequence spread spectrum (DSSS) technique ... Journal of Fundamental and Applied Sciences ... Keywords: DSSS, LTE network; Wi-Fi network; SINR; interference management and interference power.

Complex Virus-Host Interactions Involved in the Regulation of Classical Swine Fever Virus Replication: A Minireview.

Science.gov (United States)

Li, Su; Wang, Jinghan; Yang, Qian; Naveed Anwar, Muhammad; Yu, Shaoxiong; Qiu, Hua-Ji

2017-07-05

Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is one of the most devastating epizootic diseases of pigs in many countries. Viruses are small intracellular parasites and thus rely on the cellular factors for replication. Fundamental aspects of CSFV-host interactions have been well described, such as factors contributing to viral attachment, modulation of genomic replication and translation, antagonism of innate immunity, and inhibition of cell apoptosis. However, those host factors that participate in the viral entry, assembly, and release largely remain to be elucidated. In this review, we summarize recent progress in the virus-host interactions involved in the life cycle of CSFV and analyze the potential mechanisms of viral entry, assembly, and release. We conclude with future perspectives and highlight areas that require further understanding.

Mutational analysis of the hypervariable region of hepatitis e virus reveals its involvement in the efficiency of viral RNA replication.

Science.gov (United States)

Pudupakam, R S; Kenney, Scott P; Córdoba, Laura; Huang, Yao-Wei; Dryman, Barbara A; Leroith, Tanya; Pierson, F William; Meng, Xiang-Jin

2011-10-01

The RNA genome of the hepatitis E virus (HEV) contains a hypervariable region (HVR) in ORF1 that tolerates small deletions with respect to infectivity. To further investigate the role of the HVR in HEV replication, we constructed a panel of mutants with overlapping deletions in the N-terminal, central, and C-terminal regions of the HVR by using a genotype 1 human HEV luciferase replicon and analyzed the effects of deletions on viral RNA replication in Huh7 cells. We found that the replication levels of the HVR deletion mutants were markedly reduced in Huh7 cells, suggesting a role of the HVR in viral replication efficiency. To further verify the results, we constructed HVR deletion mutants by using a genetically divergent, nonmammalian avian HEV, and similar effects on viral replication efficiency were observed when the avian HEV mutants were tested in LMH cells. Furthermore, the impact of complete HVR deletion on virus infectivity was tested in chickens, using an avian HEV mutant with a complete HVR deletion. Although the deletion mutant was still replication competent in LMH cells, the complete HVR deletion resulted in a loss of avian HEV infectivity in chickens. Since the HVR exhibits extensive variations in sequence and length among different HEV genotypes, we further examined the interchangeability of HVRs and demonstrated that HVR sequences are functionally exchangeable between HEV genotypes with regard to viral replication and infectivity in vitro, although genotype-specific HVR differences in replication efficiency were observed. The results showed that although the HVR tolerates small deletions with regard to infectivity, it may interact with viral and host factors to modulate the efficiency of HEV replication.

Regulated Electric Drainage and its Interference with Track Circuits

Directory of Open Access Journals (Sweden)

Vaclav Kolar

2018-01-01

Full Text Available Electric drainage is a power electronic device used to protect underground metal devices (such as piping from the corrosive effects of stray currents. Stray currents are usually caused by DC electric traction, such as trams or railways. In places where stray currents leave the underground device and return into rails, they cause significant electrochemical corrosion of buried devices. The principle of electric drainage is based on electrical connection between the underground device and electric traction rails, which ensures that current flows through this connection, instead of flowing into the ground. Nowadays, the most widely used type is regulated electric drainage, where current is regulated by means of Pulse Width Modulation (PWM. Because of this modulation, current flowing through the drainage contains harmonic components with different frequencies. In modern railways, track circuits are often used as an important part of the track security system. For safe operation, it is necessary to ensure that frequencies generated by the drainage do not interfere with track circuits. This paper describes the design of a regulated drainage control system, with regard to its compatibility with track circuits and this paper contains related computer simulations and discussion of the results

Cognitive-motor dual-task interference modulates mediolateral dynamic stability during gait in post-stroke individuals.

Science.gov (United States)

Tisserand, R; Armand, S; Allali, G; Schnider, A; Baillieul, S

2018-04-01

Gait asymmetry and dynamic balance impairments observed in post-stroke individuals increase their risk of fall. Moreover, walking while performing a cognitive task (i.e. dual-task) disturbs the control of balance in post-stroke individuals. Here we investigated the mediolateral dynamic stability in twenty-two community-dwelling participants (12 post-strokes and 10 healthy controls) while walking in single-task (normal gait) and four different dual-tasks (cognitive-motor interference). Positions of the extrapolated center of mass and mediolateral widths of both margin of stability and base of support were extracted from 35 marker trajectories. Post-stroke participants presented larger margin of stability and base of support than controls during single-task (both p dual-task was found between groups. In post-stroke participants, dual-task induced slight modification of the mediolateral stability strategy, as the margin of stability was not different between the two limbs at foot-strike, and significantly reduced the performance in every cognitive task. Post-stroke participants increased their dynamic stability in the frontal plane in single-task by extending their base of support and mainly relying on their non-paretic limb. Under cognitive-motor interference (dual-task), post-stroke participants prioritized dynamic stability over cognitive performance to ensure a safe locomotion. Thus, rehabilitation programs should consider both dynamic balance and dual-task training, even at a chronic delay following stroke, to reduce the risk of fall in post-stroke individuals. Copyright © 2018 Elsevier B.V. All rights reserved.

Replication-deficient mutant Herpes Simplex Virus-1 targets professional antigen presenting cells and induces efficient CD4+ T helper responses.

Science.gov (United States)

Fiorentini, Simona; Marconi, Peggy; Avolio, Manuela; Marini, Elena; Garrafa, Emirena; Caracciolo, Sonia; Rossi, Daniele; Bozac, Alexandra; Becker, Pablo D; Gentili, Francesca; Facchetti, Fabio; Guzman, Carlos A; Manservigi, Roberto; Caruso, Arnaldo

2007-07-01

Both neutralizing antibodies and cytotoxic T-cells are necessary to control a viral infection. However, vigorous T helper responses are essential for their elicitation and maintenance. Here we show that a recombinant replication-deficient Herpes Simplex Virus (HSV)-1 vector encoding the Human Immunodeficiency Virus (HIV)-1 matrix protein p17 (T0-p17) was capable of infecting professional antigen presenting cells (APCs) in vitro and in vivo. The injection of T0-p17 in the mouse dermis generated a strong p17-specific CD4+ T helper response preceding both p17-specific humoral and effector T cell responses. Moreover, we show that T0-p17 infection did not interfere with the endogenous processing of the transgene encoded antigen, since infected APCs were able to evoke a strong recall response in vitro. Our results demonstrate that replication-deficient HSV vectors can be appealing candidates for the development of vaccines able to trigger T helper responses.

The Hepatitis B Virus (HBV) HBx Protein Activates AKT To Simultaneously Regulate HBV Replication and Hepatocyte Survival

Science.gov (United States)

Rawat, Siddhartha

2014-01-01

ABSTRACT Chronic infection with hepatitis B virus (HBV) is a risk factor for developing liver diseases such as hepatocellular carcinoma (HCC). HBx is a multifunctional protein encoded by the HBV genome; HBx stimulates HBV replication and is thought to play an important role in the development of HBV-associated HCC. HBx can activate the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway in some cell lines; however, whether HBx regulates PI3K/AKT signaling in normal hepatocytes has not been evaluated. In studies described here, we assessed HBx activation of PI3K/AKT signaling in an ex vivo model of cultured primary hepatocytes and determined how this HBx activity affects HBV replication. We report that HBx activates AKT in primary hepatocytes and that the activation of AKT decreases HBV replication and HBV mRNA and core protein levels. We show that the transcription factor hepatocyte nuclear factor 4α (HNF4α) is a target of HBx-regulated AKT, and we link HNF4α to HBx-regulated AKT modulation of HBV transcription and replication. Although we and others have shown that HBx stimulates and is likely required for HBV replication, we now report that HBx also activates signals that can diminish the overall level of HBV replication. While this may seem counterintuitive, we show that an important effect of HBx activation of AKT is inhibition of apoptosis. Consequently, our studies suggest that HBx balances HBV replication and cell survival by stimulating signaling pathways that enhance hepatocyte survival at the expense of higher levels of HBV replication. IMPORTANCE Chronic hepatitis B virus (HBV) infection is a common cause of the development of liver cancer. Regulation of cell signaling pathways by the HBV HBx protein is thought to influence the development of HBV-associated liver cancer. HBx stimulates, and may be essential for, HBV replication. We show that HBx activates AKT in hepatocytes to reduce HBV replication. While this seems contradictory to an

Surface microstructure replication in injection molding

DEFF Research Database (Denmark)

Theilade, Uffe Arlø; Hansen, Hans Nørgaard

2006-01-01

topography is transcribed onto the plastic part through complex mechanisms. This replication, however, is not perfect, and the replication quality depends on the plastic material properties, the topography itself, and the process conditions. This paper describes and discusses an investigation of injection...... molding of surface microstructures. The fundamental problem of surface microstructure replication has been studied. The research is based on specific microstructures as found in lab-on-a-chip products and on rough surfaces generated from EDM (electro discharge machining) mold cavities. Emphasis is put...... on the ability to replicate surface microstructures under normal injection-molding conditions, i.e., with commodity materials within typical process windows. It was found that within typical process windows the replication quality depends significantly on several process parameters, and especially the mold...

Quantum eraser for three-slit interference

Indian Academy of Sciences (India)

Naveed Ahmad Shah

2017-11-09

Nov 9, 2017 ... Abstract. It is well known that in a two-slit interference experiment, if the information, on which of the two paths the particle followed, is stored in a quantum path detector, the interference is destroyed. However, in a set-up where this path information is 'erased', the interference can reappear. Such a set-up is ...

Activation of human herpesvirus replication by apoptosis.

Science.gov (United States)

Prasad, Alka; Remick, Jill; Zeichner, Steven L

2013-10-01

A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance.

RNA interference-based resistance against a legume mastrevirus

Directory of Open Access Journals (Sweden)

Mansoor Shahid

2011-11-01

Full Text Available Abstract Background RNA interference (RNAi is a homology-dependant gene silencing mechanism and has been widely used to engineer resistance in plants against RNA viruses. However, its usefulness in delivering resistance against plant DNA viruses belonging to family Geminiviridae is still being debated. Although the RNAi approach has been shown, using a transient assay, to be useful in countering monocotyledonous plant-infecting geminiviruses of the genus Mastrevirus, it has yet to be investigated as a means of delivering resistance to dicot-infecting mastreviruses. Chickpea chlorotic dwarf Pakistan virus (CpCDPKV is a legume-infecting mastrevirus that affects chickpea and other leguminous crops in Pakistan. Results Here a hairpin (hpRNAi construct containing sequences encompassing part of replication-associated protein gene, intergenic region and part of the movement protein gene of CpCDPKV under the control of the Cauliflower mosaic virus 35S promoter has been produced and stably transformed into Nicotiana benthamiana. Plants harboring the hairpin construct were challenged with CpCDPKV. All non-transgenic N. benthamiana plants developed symptoms of CpCDPKV infection within two weeks post-inoculation. In contrast, none of the inoculated transgenic plants showed symptoms of infection and no viral DNA could be detected by Southern hybridization. A real-time quantitative PCR analysis identified very low-level accumulation of viral DNA in the inoculated transgenic plants. Conclusions The results presented show that the RNAi-based resistance strategy is useful in protecting plants from a dicot-infecting mastrevirus. The very low levels of virus detected in plant tissue of transgenic plants distal to the inoculation site suggest that virus movement and/or viral replication was impaired leading to plants that showed no discernible signs of virus infection.

Intrinsically stable phase-modulated polarization encoding system for quantum key distribution

Energy Technology Data Exchange (ETDEWEB)

Liu Xiaobao [Laboratory of Photonic Information Technology, School for Information and Optoelectronic Science and Engineering, South China Normal University, Guangzhou 510006 (China); Liao Changjun [Laboratory of Photonic Information Technology, School for Information and Optoelectronic Science and Engineering, South China Normal University, Guangzhou 510006 (China)], E-mail: chliao@scnu.edu.cn; Mi Jinglong; Wang Jindong; Liu Songhao [Laboratory of Photonic Information Technology, School for Information and Optoelectronic Science and Engineering, South China Normal University, Guangzhou 510006 (China)

2008-12-22

We demonstrate experimentally an intrinsically stable polarization coding and decoding system composed of optical-fiber Sagnac interferometers with integrated phase modulators for quantum key distribution. An interference visibility of 98.35% can be kept longtime during the experiment without any efforts of active compensation for coding all four desired polarization states.

Electromagnetic interference: a radiant future!

NARCIS (Netherlands)

Leferink, Frank Bernardus Johannes

2015-01-01

Although Electromagnetic Interference and Electromagnetic Compatibility are well established domains, the introduction of new technologies results in new challenges. Changes in both measurement techniques, and technological trends resulting in new types of interference are described. These are the

Interference between electric and magnetic concepts in introductory physics

Directory of Open Access Journals (Sweden)

Thomas M. Scaife

2011-03-01

Full Text Available We investigate student confusion of concepts of electric and magnetic force. At various times during a traditional university-level course, we administered a series of simple questions about the direction of force on a charged particle moving through either an electric or a magnetic field. We find that after electric force instruction but before magnetic force instruction most students answer electric force questions correctly, and we replicate well-known results that many students incorrectly answer that magnetic forces are in the same direction as the magnetic field. After magnetic force instruction, most students answer magnetic force questions correctly, but surprisingly many students incorrectly answer that electric forces are perpendicular to electric fields, as would happen if a student confused electric forces with magnetic forces. As a further indication of interference between electric and magnetic concepts, we also find that students’ responses depend on whether electric or magnetic force questions are posed first, and this effect depends on whether electric or magnetic force was most recently taught.

Auditory and motor imagery modulate learning in music performance

Directory of Open Access Journals (Sweden)

Rachel M. Brown

2013-07-01

Full Text Available Skilled performers such as athletes or musicians can improve their performance by imagining the actions or sensory outcomes associated with their skill. Performers vary widely in their auditory and motor imagery abilities, and these individual differences influence sensorimotor learning. It is unknown whether imagery abilities influence both memory encoding and retrieval. We examined how auditory and motor imagery abilities influence musicians’ encoding (during Learning, as they practiced novel melodies, and retrieval (during Recall of those melodies. Pianists learned melodies by listening without performing (auditory learning or performing without sound (motor learning; following Learning, pianists performed the melodies from memory with auditory feedback (Recall. During either Learning (Experiment 1 or Recall (Experiment 2, pianists experienced either auditory interference, motor interference, or no interference. Pitch accuracy (percentage of correct pitches produced and temporal regularity (variability of quarter-note interonset intervals were measured at Recall. Independent tests measured auditory and motor imagery skills. Pianists’ pitch accuracy was higher following auditory learning than following motor learning and lower in motor interference conditions (Experiments 1 and 2. Both auditory and motor imagery skills improved pitch accuracy overall. Auditory imagery skills modulated pitch accuracy encoding (Experiment 1: Higher auditory imagery skill corresponded to higher pitch accuracy following auditory learning with auditory or motor interference, and following motor learning with motor or no interference. These findings suggest that auditory imagery abilities decrease vulnerability to interference and compensate for missing auditory feedback at encoding. Auditory imagery skills also influenced temporal regularity at retrieval (Experiment 2: Higher auditory imagery skill predicted greater temporal regularity during Recall in the

Outage Analysis of Mixed Underlay Cognitive RF MIMO and FSO Relaying with Interference Reduction

KAUST Repository

Al-Qahtani, Fawaz S.; El-Malek, Ahmed H. Abd; Ansari, Imran S.; Radaydeh, Redha Mahmoud Mesleh; Zummo, Salam A.

2017-01-01

In this paper, we study the outage performance of multiuser mixed underlay radio frequency (RF)/multidestinations free-space optical (FSO) links. For RF links, we consider a secondary network with multiple users that can communicate with multiple destinations through a relaying node. The relay is equipped with an antenna array at the RF side, and it uses the amplify-and-forward (AF) protocol. The primary users (PUs) are equipped with multiple antennas at transmit and receive nodes. The RF link is subjected to the aggregate PUs interference effect on the secondary network. To reduce the effect of PUs interference on secondary network at the relay node, two interference cancellation (IC) schemes are adopted, which vary in terms of complexity and achieved performance. On the other hand, the multidestination FSO links can be exploited to further enhance the quality of the second hop, and their associated channel models account for pointing errors, intensity modulation/direct detection, and heterodyne detection. For the aforementioned system model, we obtain exact and asymptotic closed-form expressions for the end-to-end outage probability. To further enhance system performance, optimal power allocation between the two hops is obtained based on the derived asymptotic outage probability expressions.

Outage Analysis of Mixed Underlay Cognitive RF MIMO and FSO Relaying with Interference Reduction

KAUST Repository

Al-Qahtani, Fawaz S.

2017-03-22

In this paper, we study the outage performance of multiuser mixed underlay radio frequency (RF)/multidestinations free-space optical (FSO) links. For RF links, we consider a secondary network with multiple users that can communicate with multiple destinations through a relaying node. The relay is equipped with an antenna array at the RF side, and it uses the amplify-and-forward (AF) protocol. The primary users (PUs) are equipped with multiple antennas at transmit and receive nodes. The RF link is subjected to the aggregate PUs interference effect on the secondary network. To reduce the effect of PUs interference on secondary network at the relay node, two interference cancellation (IC) schemes are adopted, which vary in terms of complexity and achieved performance. On the other hand, the multidestination FSO links can be exploited to further enhance the quality of the second hop, and their associated channel models account for pointing errors, intensity modulation/direct detection, and heterodyne detection. For the aforementioned system model, we obtain exact and asymptotic closed-form expressions for the end-to-end outage probability. To further enhance system performance, optimal power allocation between the two hops is obtained based on the derived asymptotic outage probability expressions.

Evolution of Replication Machines

Science.gov (United States)

Yao, Nina Y.; O'Donnell, Mike E.

2016-01-01

The machines that decode and regulate genetic information require the translation, transcription and replication pathways essential to all living cells. Thus, it might be expected that all cells share the same basic machinery for these pathways that were inherited from the primordial ancestor cell from which they evolved. A clear example of this is found in the translation machinery that converts RNA sequence to protein. The translation process requires numerous structural and catalytic RNAs and proteins, the central factors of which are homologous in all three domains of life, bacteria, archaea and eukarya. Likewise, the central actor in transcription, RNA polymerase, shows homology among the catalytic subunits in bacteria, archaea and eukarya. In contrast, while some “gears” of the genome replication machinery are homologous in all domains of life, most components of the replication machine appear to be unrelated between bacteria and those of archaea and eukarya. This review will compare and contrast the central proteins of the “replisome” machines that duplicate DNA in bacteria, archaea and eukarya, with an eye to understanding the issues surrounding the evolution of the DNA replication apparatus. PMID:27160337

DNA replication origins—where do we begin?

Science.gov (United States)

Prioleau, Marie-Noëlle; MacAlpine, David M.

2016-01-01

For more than three decades, investigators have sought to identify the precise locations where DNA replication initiates in mammalian genomes. The development of molecular and biochemical approaches to identify start sites of DNA replication (origins) based on the presence of defining and characteristic replication intermediates at specific loci led to the identification of only a handful of mammalian replication origins. The limited number of identified origins prevented a comprehensive and exhaustive search for conserved genomic features that were capable of specifying origins of DNA replication. More recently, the adaptation of origin-mapping assays to genome-wide approaches has led to the identification of tens of thousands of replication origins throughout mammalian genomes, providing an unprecedented opportunity to identify both genetic and epigenetic features that define and regulate their distribution and utilization. Here we summarize recent advances in our understanding of how primary sequence, chromatin environment, and nuclear architecture contribute to the dynamic selection and activation of replication origins across diverse cell types and developmental stages. PMID:27542827

HBV subgenotypes F1b and F4 replication induces an incomplete autophagic process in hepatocytes: Role of BCP and preCore mutations.

Science.gov (United States)

Elizalde, María Mercedes; Pérez, Paula Soledad; Sevic, Ina; Grasso, Daniel; Ropolo, Alejandro; Barbini, Luciana; Campos, Rodolfo Héctor; Vaccaro, María Inés; Flichman, Diego Martín

2018-01-01

Hepatitis B virus (HBV) genotypes and mutants have been associated with differences in clinical and virological characteristics. Autophagy is a cellular process that degrades long-lived proteins and damaged organelles. Viruses have evolved mechanisms to alter this process to survive in host cells. In this work, we studied the modulation of autophagy by the replication of HBV subgenotypes F1b and F4, and the naturally occurring mutants BCP and preCore. HBV subgenotypes F1b and F4 replication induced accumulation of autophagosomes in hepatoma cells. However, no autophagic protein degradation was observed, indicating a blockage of autophagic flux at later stages. This inhibition of autophagy flux might be due to an impairment of lysosomal acidification in hepatoma cells. Moreover, HBV-mediated autophagy modulation was independent of the viral subgenotypes and enhanced in viruses with BCP and preCore naturally occurring mutations. These results contribute to understand the mechanisms by which different HBV variants contribute to the pathogenesis of HBV infections. In addition, this study is the first to describe the role that two highly prevalent naturally occurring mutations exert on the modulation of HBV-induced autophagy.

Early intranuclear replication of African swine fever virus genome modifies the landscape of the host cell nucleus.

Science.gov (United States)

Simões, Margarida; Martins, Carlos; Ferreira, Fernando

2015-12-02

Although African swine fever virus (ASFV) replicates in viral cytoplasmic factories, the presence of viral DNA within the host cell nucleus has been previously reported to be essential for productive infection. Herein, we described, for the first time, the intranuclear distribution patterns of viral DNA replication events, preceding those that occur in the cytoplasmic compartment. Using BrdU pulse-labelling experiments, newly synthesized ASFV genomes were exclusively detected inside the host cell nucleus at the early phase of infection, both in swine monocyte-derived macrophages (MDMs) and Vero cells. From 8hpi onwards, BrdU labelling was only observed in ASFV cytoplasmic factories. Our results also show that ASFV specifically activates the Ataxia Telangiectasia Mutated Rad-3 related (ATR) pathway in ASFV-infected swine MDMs from the early phase of infection, most probably because ASFV genome is recognized as foreign DNA. Morphological changes of promyelocytic leukaemia nuclear bodies (PML-NBs), nuclear speckles and Cajal bodies were also found in ASFV-infected swine MDMs, strongly suggesting the viral modulation of cellular antiviral responses and cellular transcription, respectively. As described for other viral infections, the nuclear reorganization that takes place during ASFV infection may also provide an environment that favours its intranuclear replication events. Altogether, our results contribute for a better understanding of ASFV replication strategies, starting with an essential intranuclear DNA replication phase which induces host nucleus changes towards a successful viral infection. Copyright © 2015 Elsevier B.V. All rights reserved.

Intensity-based fibre-optic sensing system using contrast modulation of subcarrier interference pattern

Science.gov (United States)

Adamovsky, G.; Sherer, T. N.; Maitland, D. J.

1989-01-01

A novel technique to compensate for unwanted intensity losses in a fiber-optic sensing system is described. The technique involves a continuous sinusoidal modulation of the light source intensity at radio frequencies and an intensity sensor placed in an unbalanced interferometer. The system shows high sensitivity and stability.

Emissions of Photonic Crystal Waveguides with Discretely Modulated Surfaces

International Nuclear Information System (INIS)

Dong-Hua, Tang; Li-Xue, Chen; Yan, Liu; Xiu-Dong, Sun; Wei-Qiang, Ding

2009-01-01

Transmission properties of photonic crystal (PC) waveguides with discretely modulated exit surfaces are investigated numerically using the unite-difference time-domain (FDTD) method. Unlike the case of periodically modulated surfaces, where the transmission beam tends to be a single and directional beam, when the exit surfaces are modulated only at several discrete points, the emission power tends to split into multiple and directional beams. We explain this phenomenon using a multiple point source interference model. Based on these results, we propose a 1-to-N beam splitter, and numerically realized high efficiency coupling between a PC sub-wavelength waveguide and three traditional dielectric waveguides with a total efficiency larger than 92%. This simple, easy fabrication, and controllable mechanism may find more potential applications in integrated optical circuits. (fundamental areas of phenomenology(including applications))

Cell-Free and Cell-Based Approaches to Explore the Roles of Host Membranes and Lipids in the Formation of Viral Replication Compartment Induced by Tombusviruses.

Science.gov (United States)

Nagy, Peter D; Pogany, Judit; Xu, Kai

2016-03-03

Plant positive strand RNA viruses are intracellular infectious agents that take advantage of cellular lipids and membranes to support replication and protect viral RNA from degradation by host antiviral responses. In this review, we discuss how Tomato bushy stunt virus (TBSV) co-opts lipid transfer proteins and modulates lipid metabolism and transport to facilitate the assembly of the membrane-bound viral replicase complexes within intricate replication compartments. Identification and characterization of the proviral roles of specific lipids and proteins involved in lipid metabolism based on results from yeast (Saccharomyces cerevisiae) model host and cell-free approaches are discussed. The review also highlights the advantage of using liposomes with chemically defined composition to identify specific lipids required for TBSV replication. Remarkably, all the known steps in TBSV replication are dependent on cellular lipids and co-opted membranes.

An Interference-Aware Traffic-Priority-Based Link Scheduling Algorithm for Interference Mitigation in Multiple Wireless Body Area Networks

Directory of Open Access Journals (Sweden)

Thien T. T. Le

2016-12-01

Full Text Available Currently, wireless body area networks (WBANs are effectively used for health monitoring services. However, in cases where WBANs are densely deployed, interference among WBANs can cause serious degradation of network performance and reliability. Inter-WBAN interference can be reduced by scheduling the communication links of interfering WBANs. In this paper, we propose an interference-aware traffic-priority-based link scheduling (ITLS algorithm to overcome inter-WBAN interference in densely deployed WBANs. First, we model a network with multiple WBANs as an interference graph where node-level interference and traffic priority are taken into account. Second, we formulate link scheduling for multiple WBANs as an optimization model where the objective is to maximize the throughput of the entire network while ensuring the traffic priority of sensor nodes. Finally, we propose the ITLS algorithm for multiple WBANs on the basis of the optimization model. High spatial reuse is also achieved in the proposed ITLS algorithm. The proposed ITLS achieves high spatial reuse while considering traffic priority, packet length, and the number of interfered sensor nodes. Our simulation results show that the proposed ITLS significantly increases spatial reuse and network throughput with lower delay by mitigating inter-WBAN interference.

Chromosomal DNA replication of Vicia faba cells

International Nuclear Information System (INIS)

Ikushima, Takaji

1976-01-01

The chromosomal DNA replication of higher plant cells has been investigated by DNA fiber autoradiography. The nuclear DNA fibers of Vicia root meristematic cells are organized into many tandem arrays of replication units or replicons which exist as clusters with respect to replication. DNA is replicated bidirectionally from the initiation points at the average rate of 0.15 μm/min at 20 0 C, and the average interinitiation interval is about 16 μm. The manner of chromosomal DNA replication in this higher plant is similar to that found in other eukaryotic cells at a subchromosomal level. (auth.)

Fringe counting method for synthetic phase with frequency-modulated laser diodes

International Nuclear Information System (INIS)

Onodera, Ribun; Sakuyama, Munechika; Ishii, Yukihiro

2007-01-01

Fringe counting method with laser diodes (LDs) for displacement measurement has been constructed. Two LDs are frequency modulated by mutually inverted sawtooth currents on an unbalanced two-beam interferometer. The mutually inverted sawtooth-current modulation of LDs produces interference fringe signals with opposite signs for respective wavelengths. The two fringe signals are fed to an electronic mixer to produce a synthetic fringe signal with a reduced sensitivity to the synthetic wavelength. Synthetic fringe pulses derived from the synthetic fringe signal make a fringe counting system possible for faster movement of the tested mirror

Surface micro topography replication in injection moulding

DEFF Research Database (Denmark)

Arlø, Uffe Rolf

Thermoplastic injection moulding is a widely used industrial process that involves surface generation by replication. The surface topography of injection moulded plastic parts can be important for aesthetical or technical reasons. With the emergence of microengineering and nanotechnology additional...... importance of surface topography follows. In general the replication is not perfect and the topography of the plastic part differs from the inverse topography of the mould cavity. It is desirable to be able to control the degree of replication perfection or replication quality. This requires an understanding...... of the physical mechanisms of replication. Such understanding can lead to improved process design and facilitate in-line process quality control with respect to surface properties. The purpose of the project is to identify critical factors that affect topography replication quality and to obtain an understanding...

DNA replication in ultraviolet light irradiated Chinese hamster cells: the nature of replicon inhibition and post-replication repair

International Nuclear Information System (INIS)

Doniger, J.

1978-01-01

DNA replication in ultraviolet light irradiated Chinese hamster cells was studied using techniques of DNA fiber autoradiography and alkaline sucrose sedimentation. Bidirectionally growing replicons were observed in the autoradiograms independent of the irradiation conditions. After a dose of 5 J/m 2 at 254 nm the rate of fork progression was the same as in unirradiated cells, while the rate of replication was reduced by 50%. After a dose of 10J/m 2 the rate of fork progression was reduced 40%, while the replication rate was only 25% of normal. Therefore, at low doses of ultraviolet light irradiation, the inhibition of DNA replication is due to reduction in the number of functioning replicons, while at higher doses the rate of fork progression is also slowed. Those replicons which no longer function after irradiation are blocked in fork movement rather than replicon initiation. After irradiation, pulse label was first incorporated into short nascent strands, the average size of which was approximately equal to the distance between pyrimidine dimers. Under conditions where post-replication repair occurs these short strands were eventually joined into larger pieces. Finally, the data show that slowing post-replication repair with caffeine does not slow fork movement. The results presented here support the post-replication repair model of 'gapped synthesis' and rule out a major role for 'replicative bypass'. (author)

Dual-polarization interference microscopy for advanced quantification of phase associated with the image field.

Science.gov (United States)

Bouchal, Petr; Chmelík, Radim; Bouchal, Zdeněk

2018-02-01

A new concept of dual-polarization spatial light interference microscopy (DPSLIM) is proposed and demonstrated experimentally. The method works with two orthogonally polarized modes in which signal and reference waves are combined to realize the polarization-sensitive phase-shifting, thus allowing advanced reconstruction of the phase associated with the image field. The image phase is reconstructed directly from four polarization encoded interference records by a single step processing. This is a progress compared with common methods, in which the phase of the image field is reconstructed using the optical path difference and the amplitudes of interfering waves, which are calculated in multiple-step processing of the records. The DPSLIM is implemented in a common-path configuration using a spatial light modulator, which is connected to a commercial microscope Nikon E200. The optical performance of the method is demonstrated in experiments using both polystyrene microspheres and live LW13K2 cells.

Dynamics of Escherichia coli Chromosome Segregation during Multifork Replication

DEFF Research Database (Denmark)

Nielsen, Henrik Jørck; Youngren, Brenda; Hansen, Flemming G.

2007-01-01

Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division, the chro......Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division......, the chromosomes contain multiple replication forks and must be segregated while this complex pattern of replication is still ongoing. Here, we show that replication and segregation continue in step, starting at the origin and progressing to the replication terminus. Thus, early-replicated markers on the multiple......-branched chromosomes continue to separate soon after replication to form separate protonucleoids, even though they are not segregated into different daughter cells until later generations. The segregation pattern follows the pattern of chromosome replication and does not follow the cell division cycle. No extensive...

Nonequilibrium Entropic Bounds for Darwinian Replicators

Directory of Open Access Journals (Sweden)

Jordi Piñero

2018-01-01

Full Text Available Life evolved on our planet by means of a combination of Darwinian selection and innovations leading to higher levels of complexity. The emergence and selection of replicating entities is a central problem in prebiotic evolution. Theoretical models have shown how populations of different types of replicating entities exclude or coexist with other classes of replicators. Models are typically kinetic, based on standard replicator equations. On the other hand, the presence of thermodynamical constraints for these systems remain an open question. This is largely due to the lack of a general theory of statistical methods for systems far from equilibrium. Nonetheless, a first approach to this problem has been put forward in a series of novel developements falling under the rubric of the extended second law of thermodynamics. The work presented here is twofold: firstly, we review this theoretical framework and provide a brief description of the three fundamental replicator types in prebiotic evolution: parabolic, malthusian and hyperbolic. Secondly, we employ these previously mentioned techinques to explore how replicators are constrained by thermodynamics. Finally, we comment and discuss where further research should be focused on.

Quantum Interference and Coherence Theory and Experiments

CERN Document Server

Ficek, Zbigniew; Rhodes, William T; Asakura, Toshimitsu; Brenner, Karl-Heinz; Hänsch, Theodor W; Kamiya, Takeshi; Krausz, Ferenc; Monemar, Bo; Venghaus, Herbert; Weber, Horst; Weinfurter, Harald

2005-01-01

For the first time, this book assembles in a single volume accounts of many phenomena involving quantum interference in optical fields and atomic systems. It provides detailed theoretical treatments and experimental analyses of such phenomena as quantum erasure, quantum lithography, multi-atom entanglement, quantum beats, control of decoherence, phase control of quantum interference, coherent population trapping, electromagnetically induced transparency and absorption, lasing without inversion, subluminal and superluminal light propagation, storage of photons, quantum interference in phase space, interference and diffraction of cold atoms, and interference between Bose-Einstein condensates. This book fills a gap in the literature and will be useful to both experimentalists and theoreticians.

Rank-Constrained Beamforming for MIMO Cognitive Interference Channel

Directory of Open Access Journals (Sweden)

Duoying Zhang

2016-01-01

Full Text Available This paper considers the spectrum sharing multiple-input multiple-output (MIMO cognitive interference channel, in which multiple primary users (PUs coexist with multiple secondary users (SUs. Interference alignment (IA approach is introduced that guarantees that secondary users access the licensed spectrum without causing harmful interference to the PUs. A rank-constrained beamforming design is proposed where the rank of the interferences and the desired signals is concerned. The standard interferences metric for the primary link, that is, interference temperature, is investigated and redesigned. The work provides a further improvement that optimizes the dimension of the interferences in the cognitive interference channel, instead of the power of the interference leakage. Due to the nonconvexity of the rank, the developed optimization problems are further approximated as convex form and are solved via choosing the transmitter precoder and receiver subspace iteratively. Numerical results show that the proposed designs can improve the achievable degree of freedom (DoF of the primary links and provide the considerable sum rate for both secondary and primary transmissions under the rank constraints.

Rescue from replication stress during mitosis.

Science.gov (United States)

Fragkos, Michalis; Naim, Valeria

2017-04-03

Genomic instability is a hallmark of cancer and a common feature of human disorders, characterized by growth defects, neurodegeneration, cancer predisposition, and aging. Recent evidence has shown that DNA replication stress is a major driver of genomic instability and tumorigenesis. Cells can undergo mitosis with under-replicated DNA or unresolved DNA structures, and specific pathways are dedicated to resolving these structures during mitosis, suggesting that mitotic rescue from replication stress (MRRS) is a key process influencing genome stability and cellular homeostasis. Deregulation of MRRS following oncogene activation or loss-of-function of caretaker genes may be the cause of chromosomal aberrations that promote cancer initiation and progression. In this review, we discuss the causes and consequences of replication stress, focusing on its persistence in mitosis as well as the mechanisms and factors involved in its resolution, and the potential impact of incomplete replication or aberrant MRRS on tumorigenesis, aging and disease.

Transcription factor genes essential for cell proliferation and replicative lifespan in budding yeast

Energy Technology Data Exchange (ETDEWEB)

Kamei, Yuka; Tai, Akiko; Dakeyama, Shota; Yamamoto, Kaori; Inoue, Yamato; Kishimoto, Yoshifumi; Ohara, Hiroya; Mukai, Yukio, E-mail: y_mukai@nagahama-i-bio.ac.jp

2015-07-31

Many of the lifespan-related genes have been identified in eukaryotes ranging from the yeast to human. However, there is limited information available on the longevity genes that are essential for cell proliferation. Here, we investigated whether the essential genes encoding DNA-binding transcription factors modulated the replicative lifespan of Saccharomyces cerevisiae. Heterozygous diploid knockout strains for FHL1, RAP1, REB1, and MCM1 genes showed significantly short lifespan. {sup 1}H-nuclear magnetic resonance analysis indicated a characteristic metabolic profile in the Δfhl1/FHL1 mutant. These results strongly suggest that FHL1 regulates the transcription of lifespan related metabolic genes. Thus, heterozygous knockout strains could be the potential materials for discovering further novel lifespan genes. - Highlights: • Involvement of yeast TF genes essential for cell growth in lifespan was evaluated. • The essential TF genes, FHL1, RAP1, REB1, and MCM1, regulate replicative lifespan. • Heterozygous deletion of FHL1 changes cellular metabolism related to lifespan.

Personality and Academic Motivation: Replication, Extension, and Replication

Science.gov (United States)

Jones, Martin H.; McMichael, Stephanie N.

2015-01-01

Previous work examines the relationships between personality traits and intrinsic/extrinsic motivation. We replicate and extend previous work to examine how personality may relate to achievement goals, efficacious beliefs, and mindset about intelligence. Approximately 200 undergraduates responded to the survey with a 150 participants replicating…

Mutational Analysis of the Hypervariable Region of Hepatitis E Virus Reveals Its Involvement in the Efficiency of Viral RNA Replication ▿

Science.gov (United States)

Pudupakam, R. S.; Kenney, Scott P.; Córdoba, Laura; Huang, Yao-Wei; Dryman, Barbara A.; LeRoith, Tanya; Pierson, F. William; Meng, Xiang-Jin

2011-01-01

The RNA genome of the hepatitis E virus (HEV) contains a hypervariable region (HVR) in ORF1 that tolerates small deletions with respect to infectivity. To further investigate the role of the HVR in HEV replication, we constructed a panel of mutants with overlapping deletions in the N-terminal, central, and C-terminal regions of the HVR by using a genotype 1 human HEV luciferase replicon and analyzed the effects of deletions on viral RNA replication in Huh7 cells. We found that the replication levels of the HVR deletion mutants were markedly reduced in Huh7 cells, suggesting a role of the HVR in viral replication efficiency. To further verify the results, we constructed HVR deletion mutants by using a genetically divergent, nonmammalian avian HEV, and similar effects on viral replication efficiency were observed when the avian HEV mutants were tested in LMH cells. Furthermore, the impact of complete HVR deletion on virus infectivity was tested in chickens, using an avian HEV mutant with a complete HVR deletion. Although the deletion mutant was still replication competent in LMH cells, the complete HVR deletion resulted in a loss of avian HEV infectivity in chickens. Since the HVR exhibits extensive variations in sequence and length among different HEV genotypes, we further examined the interchangeability of HVRs and demonstrated that HVR sequences are functionally exchangeable between HEV genotypes with regard to viral replication and infectivity in vitro, although genotype-specific HVR differences in replication efficiency were observed. The results showed that although the HVR tolerates small deletions with regard to infectivity, it may interact with viral and host factors to modulate the efficiency of HEV replication. PMID:21775444