Mother-Child Reminiscing and Autobiographical Memory Specificity among Preschool-Age Children

ERIC Educational Resources Information Center

Valentino, Kristin; Nuttall, Amy K.; Comas, Michelle; McDonnell, Christina G.; Piper, Brianna; Thomas, Taylor E.; Fanuele, Suzanne

2014-01-01

Overgeneral memory (OGM) refers to difficulty in retrieving specific autobiographical memories. The tendency to be overgeneral in autobiographical memory recall is more commonly observed among individuals with emotional disorders compared with those without. Despite significant advances in theory and identification of mechanisms that underlie the…

Distinct retroelement classes define evolutionary breakpoints demarcating sites of evolutionary novelty

PubMed Central

Longo, Mark S; Carone, Dawn M; Green, Eric D; O'Neill, Michael J; O'Neill, Rachel J

2009-01-01

Background Large-scale genome rearrangements brought about by chromosome breaks underlie numerous inherited diseases, initiate or promote many cancers and are also associated with karyotype diversification during species evolution. Recent research has shown that these breakpoints are nonrandomly distributed throughout the mammalian genome and many, termed "evolutionary breakpoints" (EB), are specific genomic locations that are "reused" during karyotypic evolution. When the phylogenetic trajectory of orthologous chromosome segments is considered, many of these EB are coincident with ancient centromere activity as well as new centromere formation. While EB have been characterized as repeat-rich regions, it has not been determined whether specific sequences have been retained during evolution that would indicate previous centromere activity or a propensity for new centromere formation. Likewise, the conservation of specific sequence motifs or classes at EBs among divergent mammalian taxa has not been determined. Results To define conserved sequence features of EBs associated with centromere evolution, we performed comparative sequence analysis of more than 4.8 Mb within the tammar wallaby, Macropus eugenii, derived from centromeric regions (CEN), euchromatic regions (EU), and an evolutionary breakpoint (EB) that has undergone convergent breakpoint reuse and past centromere activity in marsupials. We found a dramatic enrichment for long interspersed nucleotide elements (LINE1s) and endogenous retroviruses (ERVs) and a depletion of short interspersed nucleotide elements (SINEs) shared between CEN and EBs. We analyzed the orthologous human EB (14q32.33), known to be associated with translocations in many cancers including multiple myelomas and plasma cell leukemias, and found a conserved distribution of similar repetitive elements. Conclusion Our data indicate that EBs tracked within the class Mammalia harbor sequence features retained since the divergence of marsupials and eutherians that may have predisposed these genomic regions to large-scale chromosomal instability. PMID:19630942

Isoform Specificity of Protein Kinase Cs in Synaptic Plasticity

ERIC Educational Resources Information Center

Sossin, Wayne S.

2007-01-01

Protein kinase Cs (PKCs) are implicated in many forms of synaptic plasticity. However, the specific isoform(s) of PKC that underlie(s) these events are often not known. We have used "Aplysia" as a model system in order to investigate the isoform specificity of PKC actions due to the presence of fewer isoforms and a large number of documented…

Numerical simulation study on the optimization design of the crown shape of PDC drill bit.

PubMed

Ju, Pei; Wang, Zhenquan; Zhai, Yinghu; Su, Dongyu; Zhang, Yunchi; Cao, Zhaohui

The design of bit crown is an important part of polycrystalline diamond compact (PDC) bit design, although predecessors have done a lot of researches on the design principles of PDC bit crown, the study of the law about rock-breaking energy consumption according to different bit crown shape is not very systematic, and the mathematical model of design is over-simplified. In order to analyze the relation between rock-breaking energy consumption and bit crown shape quantificationally, the paper puts forward an idea to take "per revolution-specific rock-breaking work" as objective function, and analyzes the relationship between rock properties, inner cone angle, outer cone arc radius, and per revolution-specific rock-breaking work by means of explicit dynamic finite element method. Results show that the change law between per revolution-specific rock-breaking work and the radius of gyration is similar for rocks with different properties, it is beneficial to decrease rock-breaking energy consumption by decreasing inner cone angle or outer cone arc radius. Of course, we should also consider hydraulic structure and processing technology in the optimization design of PDC bit crown.

Detection of DNA double-strand breaks and chromosome translocations using ligation-mediated PCR and inverse PCR.

PubMed

Singh, Sheetal; Shih, Shyh-Jen; Vaughan, Andrew T M

2014-01-01

Current techniques for examining the global creation and repair of DNA double-strand breaks are restricted in their sensitivity, and such techniques mask any site-dependent variations in breakage and repair rate or fidelity. We present here a system for analyzing the fate of documented DNA breaks, using the MLL gene as an example, through application of ligation-mediated PCR. Here, a simple asymmetric double-stranded DNA adapter molecule is ligated to experimentally induced DNA breaks and subjected to seminested PCR using adapter- and gene-specific primers. The rate of appearance and loss of specific PCR products allows detection of both the break and its repair. Using the additional technique of inverse PCR, the presence of misrepaired products (translocations) can be detected at the same site, providing information on the fidelity of the ligation reaction in intact cells. Such techniques may be adapted for the analysis of DNA breaks and rearrangements introduced into any identifiable genomic location. We have also applied parallel sequencing for the high-throughput analysis of inverse PCR products to facilitate the unbiased recording of all rearrangements located at a specific genomic location.

Declarative and Procedural Memory in Danish Speaking Children with Specific Language Impairment

ERIC Educational Resources Information Center

Lum, Jarrad A. G.; Bleses, Dorthe

2012-01-01

It has been proposed that the language problems in specific language impairment (SLI) arise from basal ganglia abnormalities that lead to impairments with procedural and working memory but not declarative memory. In SLI, this profile of memory functioning has been hypothesized to underlie grammatical impairment but leave lexical knowledge…

Conserved and divergent functions of Pax6 underlie species-specific neurogenic patterns in the developing amniote brain.

PubMed

Yamashita, Wataru; Takahashi, Masanori; Kikkawa, Takako; Gotoh, Hitoshi; Osumi, Noriko; Ono, Katsuhiko; Nomura, Tadashi

2018-04-16

The evolution of unique organ structures is associated with changes in conserved developmental programs. However, characterizing the functional conservation and variation of homologous transcription factors (TFs) that dictate species-specific cellular dynamics has remained elusive. Here, we dissect shared and divergent functions of Pax6 during amniote brain development. Comparative functional analyses revealed that the neurogenic function of Pax6 is highly conserved in the developing mouse and chick pallium, whereas stage-specific binary functions of Pax6 in neurogenesis are unique to mouse neuronal progenitors, consistent with Pax6-dependent temporal regulation of Notch signaling. Furthermore, we identified that Pax6-dependent enhancer activity of Dbx1 is extensively conserved between mammals and chick, although Dbx1 expression in the developing pallium is highly divergent in these species. Our results suggest that spatiotemporal changes in Pax6-dependent regulatory programs contributed to species-specific neurogenic patterns in mammalian and avian lineages, which underlie the morphological divergence of the amniote pallial architectures. © 2018. Published by The Company of Biologists Ltd.

Detection of DNA double-strand breaks and chromosome translocations using ligation-mediated PCR and inverse PCR.

PubMed

Villalobos, Michael J; Betti, Christopher J; Vaughan, Andrew T M

2006-01-01

Current techniques for examining the global creation and repair of DNA double-strand breaks are restricted in their sensitivity, and such techniques mask any site-dependent variations in breakage and repair rate or fidelity. We present here a system for analyzing the fate of documented DNA breaks, using the MLL gene as an example, through application of ligation-mediated PCR. Here, a simple asymmetric double-stranded DNA adapter molecule is ligated to experimentally induced DNA breaks and subjected to seminested PCR using adapter and gene-specific primers. The rate of appearance and loss of specific PCR products allows detection of both the break and its repair. Using the additional technique of inverse PCR, the presence of misrepaired products (translocations) can be detected at the same site, providing information on the fidelity of the ligation reaction in intact cells. Such techniques may be adapted for the analysis of DNA breaks introduced into any identifiable genomic location.

Predicting Homophobic Behavior among Heterosexual Youth: Domain General and Sexual Orientation-Specific Factors at the Individual and Contextual Level

ERIC Educational Resources Information Center

Poteat, V. Paul; DiGiovanni, Craig D.; Scheer, Jillian R.

2013-01-01

As a form of bias-based harassment, homophobic behavior remains prominent in schools. Yet, little attention has been given to factors that underlie it, aside from bullying and sexual prejudice. Thus, we examined multiple domain general (empathy, perspective-taking, classroom respect norms) and sexual orientation-specific factors (sexual…

Hospital visits for gastrointestinal Illness after a major water main break in 2010

EPA Science Inventory

Background/Aim Water main breaks can occur due to the stresses of an aging infrastructure and changing climate. Water main breaks are a public health concern because they can cause pressure transients (specifically, abrupt decreases in water pressure/flow in the pipeline), which ...

Physical Activity Opportunities during the School Day: Classroom Teachers' Perceptions of Using Activity Breaks in the Classroom

ERIC Educational Resources Information Center

McMullen, Jaimie; Kulinna, Pamela; Cothran, Donetta

2014-01-01

The purpose of this study was to explore classroom teachers' perceptions of incorporating physical activity breaks into their classroom and to determine specific features of preferred activity breaks. These perceptions are considered within the conceptual framework of Comprehensive School Physical Activity Program (CSPAP). Twelve elementary and…

Emergent Behavior in the Macro World: Rigidity of Granular Solids

NASA Astrophysics Data System (ADS)

Chakraborty, Bulbul

2015-03-01

Diversity in the natural world emerges from the collective behavior of large numbers of interacting objects. The origin of collectively organized structures over the vast range of length scales from the subatomic to colloidal is the competition between energy and entropy. Thermal motion provides the mechanism for organization by allowing particles to explore the space of configurations. This well-established paradigm of emergent behavior breaks down for collections of macroscopic objects ranging from grains of sand to asteroids. In this macro-world of particulate systems, thermal motion is absent, and mechanical forces are all important. We lack understanding of the basic, unifying principles that underlie the emergence of order in this world. In this talk, I will explore the origin of rigidity of granular solids, and present a new paradigm for emergence of order in these athermal systems. This work has been supported by NSF-DMR 1409093 and by the W. M. Keck foundation

Perceptual Processing Affects Conceptual Processing

ERIC Educational Resources Information Center

van Dantzig, Saskia; Pecher, Diane; Zeelenberg, Rene; Barsalou, Lawrence W.

2008-01-01

According to the Perceptual Symbols Theory of cognition (Barsalou, 1999), modality-specific simulations underlie the representation of concepts. A strong prediction of this view is that perceptual processing affects conceptual processing. In this study, participants performed a perceptual detection task and a conceptual property-verification task…

Rule breaking mediates the developmental association between GABRA2 and adolescent substance abuse.

PubMed

Trucco, Elisa M; Villafuerte, Sandra; Heitzeg, Mary M; Burmeister, Margit; Zucker, Robert A

2014-12-01

This study's primary aim was to examine age-specific associations between GABRA2, rule breaking, problematic alcohol use, and substance abuse symptomatology. The secondary aim was to examine the extent to which rule breaking mediates the GABRA2-substance abuse relationship. A sample (n = 518) of primarily male (70.9%) and White (88.8%) adolescents from the Michigan Longitudinal Study was assessed from ages 11-18. Age-specific effects of GABRA2 on rule breaking, problematic alcohol use, and substance abuse symptomatology were examined using nested path models. The role of rule breaking as a mediator in the association between GABRA2 and substance abuse outcomes was tested using prospective cross-lagged path models. GABRA2 is significantly (p < 0.05) associated with rule breaking in mid- to late-adolescence, but not substance abuse symptomatology across adolescence. GABRA2 effects on problematic alcohol use and substance abuse symptomatology operate largely (45.3% and 71.1%, respectively, p < 0.05) via rule breaking in midadolescence. GABRA2 represents an early risk factor for an externalizing pathway to the development of problematic alcohol and drug use. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

The influence of self-relevant materials on working memory in dysphoric undergraduates.

PubMed

Dai, Qin; Rahman, Shaoon; Lau, Becky; Sook Kim, Hyang; Deldin, Patricia

2015-10-30

Difficulties in updating working memory (WM) may underlie problems with regulating emotions that contribute to depression. To examine the ability of updating affective materials in WM, 33 dysphoric and 34 non-dysphoric participants were asked to evaluate the self-descriptiveness of emotional adjectives and provide answers to self-relevant questions. Within 3-7 days, they completed a two-back task with a series of self-irrelevant or self-relevant emotional words (they had generated previously) and four conditions (match-set, break-set, perseveration-set, and no-set). After the WM task, an unexpected recall task was administered; controls recalled more positive self-relevant words and intrusions while dysphoric participants recalled more negative self-relevant words and intrusions. In break-set trials of the two-back task, dysphoric individuals showed slower response to self-relevant words regardless of valence. In the match-set and perseveration-set trials, dysphoric participants showed delayed response to self-related negative words. Moreover, longer reaction times for self-relevant negative words were correlated with higher rumination and worse depression. The results suggest that dysphoric undergraduates are interfered more by and have a better memory of self-relevant negative stimuli in WM, which is closely correlated with rumination. This study is among the first to confirm the potential mechanism that could underwrite the involvement of self-schema in effectively regulating negative affect. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Item Difficulty Modeling of Paragraph Comprehension Items

ERIC Educational Resources Information Center

Gorin, Joanna S.; Embretson, Susan E.

2006-01-01

Recent assessment research joining cognitive psychology and psychometric theory has introduced a new technology, item generation. In algorithmic item generation, items are systematically created based on specific combinations of features that underlie the processing required to correctly solve a problem. Reading comprehension items have been more…

Impaired Statistical Learning in Developmental Dyslexia

ERIC Educational Resources Information Center

Gabay, Yafit; Thiessen, Erik D.; Holt, Lori L.

2015-01-01

Purpose: Developmental dyslexia (DD) is commonly thought to arise from phonological impairments. However, an emerging perspective is that a more general procedural learning deficit, not specific to phonological processing, may underlie DD. The current study examined if individuals with DD are capable of extracting statistical regularities across…

Molecular shifts in limb identity underlie development of feathered feet in two domestic avian species

PubMed Central

Domyan, Eric T; Kronenberg, Zev; Infante, Carlos R; Vickrey, Anna I; Stringham, Sydney A; Bruders, Rebecca; Guernsey, Michael W; Park, Sungdae; Payne, Jason; Beckstead, Robert B; Kardon, Gabrielle; Menke, Douglas B; Yandell, Mark; Shapiro, Michael D

2016-01-01

Birds display remarkable diversity in the distribution and morphology of scales and feathers on their feet, yet the genetic and developmental mechanisms governing this diversity remain unknown. Domestic pigeons have striking variation in foot feathering within a single species, providing a tractable model to investigate the molecular basis of skin appendage differences. We found that feathered feet in pigeons result from a partial transformation from hindlimb to forelimb identity mediated by cis-regulatory changes in the genes encoding the hindlimb-specific transcription factor Pitx1 and forelimb-specific transcription factor Tbx5. We also found that ectopic expression of Tbx5 is associated with foot feathers in chickens, suggesting similar molecular pathways underlie phenotypic convergence between these two species. These results show how changes in expression of regional patterning genes can generate localized changes in organ fate and morphology, and provide viable molecular mechanisms for diversity in hindlimb scale and feather distribution. DOI: http://dx.doi.org/10.7554/eLife.12115.001 PMID:26977633

Break-even zones for cable yarding by log size

Treesearch

Chris B. LeDoux

1984-01-01

The use of cable logging to extract small pieces of residue wood may result in low rates of production and a high cost per unit of wood produced. However, the logging manager can improve yarding productivity and break-even in cable residue removal operations by using the proper planning techniques. In this study, break-even zones for specific young-growth stands were...

Preliminary examination of spring break alcohol use and related consequences.

PubMed

Lee, Christine M; Lewis, Melissa A; Neighbors, Clayton

2009-12-01

The authors examined the extent to which college student drinkers are at risk for experiencing negative alcohol-related consequences during Spring Break. A sample of first-year college student drinkers (N = 726) participated by completing an online survey assessing typical drinking, as well as Spring Break drinking and related consequences. Findings suggest Spring Break drinking was positively associated with alcohol-related consequences during Spring Break, even after controlling for sex and typical drinking. Furthermore, results indicated that typical drinking moderated the relationship between Spring Break drinking and expected zero-values (i.e., not reporting any Spring Break consequences), such that the association between Spring Break drinking and the likelihood of being a zero-score was less evident for those who are typically lighter drinkers. Identifying and examining temporal and contextually relevant events and associated drinking is critical for understanding and ultimately preventing extreme drinking and associated consequences associated with specific events like Spring Break, which place many students at high risk for experiencing acute harm. Copyright 2009 APA

Evidence for network evolution in an arabidopsis interactome map

USDA-ARS?s Scientific Manuscript database

Plants have unique features that evolved in response to their environments and ecosystems. A full account of the complex cellular networks that underlie plant-specific functions is still missing. We describe a proteome-wide binary protein-protein interaction map for the interactome network of the pl...

The Influence of Working Memory Load on Semantic Priming

ERIC Educational Resources Information Center

Heyman, Tom; Van Rensbergen, Bram; Storms, Gert; Hutchison, Keith A.; De Deyne, Simon

2015-01-01

The present research examines the nature of the different processes that have been proposed to underlie semantic priming. Specifically, it has been argued that priming arises as a result of "automatic target activation" and/or the use of strategies like prospective "expectancy generation" and "retrospective semantic…

Working Memory and Language Learning: A Review

ERIC Educational Resources Information Center

Archibald, Lisa M. D.

2017-01-01

Children with speech, language, and communication needs (SLCN) form a highly heterogeneous group, including those with an unexplained delay in language development known as specific language impairment (SLI). There is growing recognition that multiple mechanisms underlie the range of profiles observed in these children. Broadly speaking, both the…

Effects of chromatin decondensation on alternative NHEJ.

PubMed

Moscariello, Mario; Iliakis, George

2013-11-01

In cells of higher eukaryotes, repair of DNA double strand breaks (DSBs) utilizes different forms of potentially error-prone non-homologous end joining (NHEJ): canonical DNA-PK-dependent (C-NHEJ) and alternative backup pathways (A-NHEJ). In contrast to C-NHEJ, A-NHEJ shows pronounced efficiency fluctuations throughout the cell cycle and is severely compromised as cells cease proliferating and enter the plateau phase (Windhofer et al., 2007 [23]). The molecular mechanisms underpinning this response remain unknown but changes in chromatin structure are prime candidate-A-NHEJ-modulators. Since parameters beyond chromatin acetylation appear to determine A-NHEJ efficiency (Manova et al., 2012 [42,76]), we study here the role of chromatin decondensation mediated either by treatment with 5'-aza-2'-deoxycytidine (AzadC) or growth in hypotonic conditions, on A-NHEJ. We report that both treatments have no detectable effect on C-NHEJ but provoke, specifically for A-NHEJ, cell-growth-dependent effects. These results uncover for the first time a link between A-NHEJ and chromatin organization and provide means for understanding the regulatory mechanisms underpinning the growth-state dependency of A-NHEJ. A-NHEJ is implicated in the formation of chromosomal translocations and in chromosome fusions that underlie genomic instability and carcinogenesis. The observations reported here may therefore contribute to the development of drug-based A-NHEJ suppression-strategies aiming at optimizing cancer treatment outcomes and possibly also at suppressing carcinogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

Parent Emotion Representations and the Socialization of Emotion Regulation in the Family

ERIC Educational Resources Information Center

Meyer, Sara; Raikes, H. Abigail; Virmani, Elita A.; Waters, Sara; Thompson, Ross A.

2014-01-01

There is considerable knowledge of parental socialization processes that directly and indirectly influence the development of children's emotion self-regulation, but little understanding of the specific beliefs and values that underlie parents' socialization approaches. This study examined multiple aspects of parents' self-reported…

Age-Related Changes in Decision Making: Comparing Informed and Noninformed Situations

ERIC Educational Resources Information Center

Van Duijvenvoorde, Anna C. K.; Jansen, Brenda R. J.; Bredman, Joren C.; Huizenga, Hilde M.

2012-01-01

Advantageous decision making progressively develops into early adulthood, most specifically in complex and motivationally salient decision situations in which direct feedback on gains and losses is provided (Figner & Weber, 2011). However, the factors that underlie this developmental improvement in decision making are still not well understood.…

Managing Work and Family: Do Control Strategies Help?

ERIC Educational Resources Information Center

Versey, H. Shellae

2015-01-01

How can we effectively manage competing obligations from work and family without becoming overwhelmed? This question inspires the current study by examining control strategies that may facilitate better work-life balance, with a specific focus on the role of lowered aspirations and positive reappraisals, attitudes that underlie adaptive coping…

Evidence-Based Kernels: Fundamental Units of Behavioral Influence

ERIC Educational Resources Information Center

Embry, Dennis D.; Biglan, Anthony

2008-01-01

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior-influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of…

Sex on the beach: the influence of social norms and trip companion on spring break sexual behavior.

PubMed

Lewis, Melissa A; Patrick, Megan E; Mittmann, Angela; Kaysen, Debra L

2014-06-01

Spring Break trips are associated with heavy drinking and with risky sexual behavior (e.g., unprotected sex, multiple partners, unwanted sexual contact), especially for those students who go on trips with friends. The present study adds to this growing event-specific risk literature by examining Spring Break-specific normative perceptions of sexual risk behavior and the role that these perceptions and taking a trip with a friend or with a romantic partner have on Spring Break sexual behavior. College students (N = 1,540; 53.9 % female) were asked to report descriptive normative perceptions of sex with casual partners, drinking prior to sex, number of drinks prior to sex, and condom use as well as their own Spring Break drinking and sexual behaviors. Students perceived the typical same-sex student to have engaged in more frequent sexual behavior for all outcomes than students' own self-reported sexual behavior. Furthermore, results revealed that these perceptions were positively associated with behavior. The choice of travel companion (friend(s) versus romantic partner) also differentially predicted sexual behaviors. Results suggested that intervention efforts aimed at reducing risks for Spring Break trip-takers may be strongest when they incorporate corrective normative information and target those traveling with friends.

Sex on the Beach: The Influence of Social Norms and Trip Companion on Spring Break Sexual Behavior

PubMed Central

Lewis, Melissa A.; Patrick, Megan E.; Mittmann, Angela; Kaysen, Debra L.

2014-01-01

Spring Break trips are associated with heavy drinking and with risky sexual behavior (e.g., unprotected sex, multiple partners, unwanted sexual contact), especially for those students who go on trips with friends. The present study adds to this growing event-specific risk literature by examining Spring Break-specific normative perceptions of sexual risk behavior and the role that these perceptions and taking a trip with a friend or with a romantic partner have on Spring Break sexual behavior. College students (N = 1,540; 53.9% female) were asked to report descriptive normative perceptions of sex with casual partners, drinking prior to sex, number of drinks prior to sex, and condom use as well as their own Spring Break drinking and sexual behaviors. Students perceived the typical same-sex student to have engaged in more frequent sexual behavior for all outcomes than students’ own self-reported sexual behavior. Furthermore, results revealed that these perceptions were positively associated with behavior. The choice of travel companion (friend(s) vs. romantic partner) also deferentially predicted sexual behaviors. Results suggested that intervention efforts aimed at reducing risks for Spring Break trip-takers may be strongest when they incorporate corrective normative information and target those traveling with friends. PMID:24464322

Splitting the mind within the individual, nation and economy: reflections on the struggle for integration in post-war Germany.

PubMed

Plänkers, Tomas

2015-02-01

With respect to theorisations of psychical splitting, this paper explores the psychical mechanisms that underlie different forms of social splitting. The paper first outlines Freud's and Kleins different theorisations of the psychical mechanisms of splitting, where the good is split from the bad, the inside split from the outside, and the painful disavowed. I then consider the psychical mechanisms of splitting that underlie ideological supports of certain social systems, specifically that of National Socialist Germany, East Germany during the Cold War period, and neoliberal capitalism. Here, I consider ideological splits between good and evil, the relation between external and internal splits, the relation between geographical, social and internal splitting, as well as splitting as disavowal of the other. Copyright © 2015 Institute of Psychoanalysis.

Breaking bad news in cancer patients.

PubMed

Konstantis, Apostolos; Exiara, Triada

2015-01-01

In a regional hospital, many patients are newly diagnosed with cancer. Breaking the bad news in these patients and their relatives is a tough task. Many doctors are not experienced in talking to patients about death or death-related diseases. In recent years, there have been great efforts to change the current situation. The aim of this study was to investigate the experience and education of medical personnel in breaking bad news in a secondary hospital. 59 doctors from General Hospital of Komotini, Greece were included in the study. All the doctors were in clinical specialties that treated cancer patients. A brief questionnaire was developed based on current guidelines such as Baile/SPIKES framework and the ABCDE mnemonic. Residents are involved in delivering bad news less frequently than specialists. Only 21 doctors (35.59%) had specific training on breaking bad news. 20 doctors (33.90%) were aware of the available techniques and protocols on breaking bad news. 47 doctors (79.66%) had a consistent plan for breaking bad news. 57 (96.61%) delivered bad news in a quiet place, 53 (89.83%) ensured no interruptions and enough time, 53 (89.83%) used simple words and 54 (91.53%) checked for understanding and did not rush through the news. 46 doctors (77.97%) allowed relatives to determine patient's knowledge about the disease. There were low rates of specific training in breaking bad news. However, the selected location, the physician's speech and their plan were according to current guidelines.

Correlates of children’s time-specific physical activity: A review of the literature

PubMed Central

2012-01-01

Assessment of correlates of physical activity occurring at different times of the day, locations and contexts, is imperative to understanding children’s physical activity behaviour. The purpose of this review was to identify the correlates of children’s physical activity (aged 8–14 years) occurring during the school break time and after-school periods. A review was conducted of the peer-reviewed literature, published between 1990 and January 2011. A total of 22 studies (12 school break time studies, 10 after-school studies) were included in the review. Across the 22 studies, 17 studies were cross-sectional and five studies were interventions. In the school break time studies, 39 potential correlates were identified, of which gender and age were consistently associated with school break time physical activity in two or more studies, and family affluence, access to a gym, access to four or more physical activity programs and the condition of a playing field were all associated with school break time physical activity in only one study. Access to loose and fixed equipment, playground markings, size of and access to play space and the length of school break time were all positively associated with changes in school break time physical activity in intervention studies. Thirty-six potential correlates of after-school physical activity were identified. Gender (with boys more active), younger age, lower body mass index (for females), lower TV viewing/playing video games, and greater access to facilities were associated with higher levels of after-school physical activity in two or more studies. Parent supervision was negatively associated with females’ after-school physical activity in one study. This review has revealed a relatively small number of studies investigating the school break time and after-school periods in the specified age range and only a few correlates have demonstrated a consistent association with physical activity. This highlights the infancy of this area and a need for further investigation into time-specific physical activity behaviour so that interventions designed for these specific periods can target the important correlates. PMID:22546218

Quantitative Differences in Salivary Pathogen Load during Tick Transmission Underlie Strain-Specific Variation in Transmission Efficiency of Anaplasma marginale

USDA-ARS?s Scientific Manuscript database

The relative fitness of arthropod-borne pathogens within the vector can be a major determinant of pathogen prevalence within the mammalian host population. Strains of the tick-borne rickettsia Anaplasma marginale differ markedly in transmission efficiency with consequent impact on pathogen strain st...

Teaching social justice using a pedagogy of engagement.

PubMed

Belknap, Ruth Ann

2008-01-01

Teaching an undergraduate level diversity course with a health focus requires specific teaching methods. A pedagogy of engagement provides an effective strategy for exploring issues of race, class, gender, and structural inequalities that underlie health disparities. Engagement learning enhances understanding of theories of oppression and liberation presented in the course and highlights social justice issues.

Response-Specific Sex Difference in the Retention of Fear Extinction

ERIC Educational Resources Information Center

Voulo, Meagan E.; Parsons, Ryan G.

2017-01-01

Fear conditioning studies in rodents allow us to assess vulnerability factors which might underlie fear-based psychopathology such as post-traumatic stress disorder (PTSD). Despite PTSD being more prevalent in females than males, very few fear conditioning studies in rodents have tested females. Our study assessed fear conditioning and extinction…

Talker Differences in Clear and Conversational Speech: Acoustic Characteristics of Vowels

ERIC Educational Resources Information Center

Ferguson, Sarah Hargus; Kewley-Port, Diane

2007-01-01

Purpose: To determine the specific acoustic changes that underlie improved vowel intelligibility in clear speech. Method: Seven acoustic metrics were measured for conversational and clear vowels produced by 12 talkers--6 who previously were found (S. H. Ferguson, 2004) to produce a large clear speech vowel intelligibility effect for listeners with…

Early Tracking or Finally Leaving? Determinants of Early Study Success in First-Year University Students

ERIC Educational Resources Information Center

Brouwer, Jasperina; Jansen, Ellen; Hofman, Adriaan; Flache, Andreas

2016-01-01

Two theoretical approaches underlie this investigation of the determinants of early study success among first-year university students. Specifically, to extend Walberg's educational productivity model, this study draws on the expectancy-value theory of achievement motivation in a contemporary university context. The survey data came from 407…

Disaggregating tropical disease prevalence by climatic and vegetative zones within tropical west Africa

Treesearch

Carl S. Beckley; Salisu Shaban; Guy H. Palmer; Andrew T. Hudak; Susan M. Noh; James E. Futse

2016-01-01

Tropical infectious disease prevalence is dependent on many socio-cultural determinants. However, rainfall and temperature frequently underlie overall prevalence, particularly for vector-borne diseases. As a result these diseases have increased prevalence in tropical as compared to temperate regions. Specific to tropical Africa, the tendency to incorrectly...

Ability Related Differences in Schema-Guided Text Processing.

ERIC Educational Resources Information Center

Derry, Sharon J.

A study using a biasing paradigm examined four hypotheses regarding specific mechanisms thought to underlie the Assimilation-plus-Correction (A-C) theory of schema-text interactions. According to this theory, the ideas implied by a schema (type-1 ideas) are thought to be assimilated and obscured, while those ideas representing novel information…

Declarative Memory Consolidation: Mechanisms Acting during Human Sleep

ERIC Educational Resources Information Center

Gais, Steffen; Born, Jan

2004-01-01

Of late, an increasing number of studies have shown a strong relationship between sleep and memory. Here we summarize a series of our own studies in humans supporting a beneficial influence of slow-wave sleep (SWS) on declarative memory formation, and try to identify some mechanisms that might underlie this influence. Specifically, these…

Differential Effects of Music and Video Gaming During Breaks on Auditory and Visual Learning.

PubMed

Liu, Shuyan; Kuschpel, Maxim S; Schad, Daniel J; Heinz, Andreas; Rapp, Michael A

2015-11-01

The interruption of learning processes by breaks filled with diverse activities is common in everyday life. This study investigated the effects of active computer gaming and passive relaxation (rest and music) breaks on auditory versus visual memory performance. Young adults were exposed to breaks involving (a) open eyes resting, (b) listening to music, and (c) playing a video game, immediately after memorizing auditory versus visual stimuli. To assess learning performance, words were recalled directly after the break (an 8:30 minute delay) and were recalled and recognized again after 7 days. Based on linear mixed-effects modeling, it was found that playing the Angry Birds video game during a short learning break impaired long-term retrieval in auditory learning but enhanced long-term retrieval in visual learning compared with the music and rest conditions. These differential effects of video games on visual versus auditory learning suggest specific interference of common break activities on learning.

Breaking Up is Hard to do: The Impact of Unmarried Relationship Dissolution on Mental Health and Life Satisfaction

PubMed Central

Rhoades, Galena K.; Kamp Dush, Claire M.; Atkins, David C.; Stanley, Scott M.; Markman, Howard J.

2011-01-01

This study was the first to examine the impact of unmarried relationship break-up on psychological distress and life satisfaction using a within-subjects design. Among unmarried 18 to 35-year olds (N = 1295), 36.5% had one or more break-ups over a 20-month period. Experiencing a break-up was associated with an increase in psychological distress and a decline in life satisfaction (from pre- to post-dissolution). In addition, several characteristics of the relationship or of the break-up were associated with the magnitude of the changes in life satisfaction following a break-up. Specifically, having been cohabiting and having had plans for marriage were associated with larger declines in life satisfaction while having begun to date someone new was associated with smaller declines. Interestingly, having higher relationship quality at the previous wave was associated with smaller declines in life satisfaction following a break-up. No relationship or break-up characteristics were significantly associated with the magnitude of changes in psychological distress after a break-up. Existing theories are used to explain the results. Implications for clinical work and future research on unmarried relationships are also discussed. PMID:21517174

CYBERSUSY A new mechanism for supersymmetry breaking in models like the Supersymmetric Standard Model (SSM):

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dixon, John A.

2010-02-10

The SUSY breaking in Cybersusy is proportional to the VEV that breaks the gauge symmetry SU(2)xU(1) down to U(1), and it is rather specific to models like the SSM. Assuming full breaking, as explained below, for the leptons, Cybersusy predicts a spectrum of SUSY breaking that is in accord with experimental results so far. In particular, for the choice of parameters below, Cybersusy predicts that the lowest mass superpartner for the charged leptons is a charged vector boson lepton (the Velectron), which has a mass of 316 Gev. The Selectron has a mass of 771 Gev for that choice ofmore » parameters. The theory also leads to a zero cosmological constant after SUSY breaking. The mechanism generates equations that restrict models like the SSM. This version of this paper incorporates recent results and changes discovered subsequent to the talk.« less

Reanalysis of RNA-Sequencing Data Reveals Several Additional Fusion Genes with Multiple Isoforms

PubMed Central

Kangaspeska, Sara; Hultsch, Susanne; Edgren, Henrik; Nicorici, Daniel; Murumägi, Astrid; Kallioniemi, Olli

2012-01-01

RNA-sequencing and tailored bioinformatic methodologies have paved the way for identification of expressed fusion genes from the chaotic genomes of solid tumors. We have recently successfully exploited RNA-sequencing for the discovery of 24 novel fusion genes in breast cancer. Here, we demonstrate the importance of continuous optimization of the bioinformatic methodology for this purpose, and report the discovery and experimental validation of 13 additional fusion genes from the same samples. Integration of copy number profiling with the RNA-sequencing results revealed that the majority of the gene fusions were promoter-donating events that occurred at copy number transition points or involved high-level DNA-amplifications. Sequencing of genomic fusion break points confirmed that DNA-level rearrangements underlie selected fusion transcripts. Furthermore, a significant portion (>60%) of the fusion genes were alternatively spliced. This illustrates the importance of reanalyzing sequencing data as gene definitions change and bioinformatic methods improve, and highlights the previously unforeseen isoform diversity among fusion transcripts. PMID:23119097

Reanalysis of RNA-sequencing data reveals several additional fusion genes with multiple isoforms.

PubMed

Kangaspeska, Sara; Hultsch, Susanne; Edgren, Henrik; Nicorici, Daniel; Murumägi, Astrid; Kallioniemi, Olli

2012-01-01

RNA-sequencing and tailored bioinformatic methodologies have paved the way for identification of expressed fusion genes from the chaotic genomes of solid tumors. We have recently successfully exploited RNA-sequencing for the discovery of 24 novel fusion genes in breast cancer. Here, we demonstrate the importance of continuous optimization of the bioinformatic methodology for this purpose, and report the discovery and experimental validation of 13 additional fusion genes from the same samples. Integration of copy number profiling with the RNA-sequencing results revealed that the majority of the gene fusions were promoter-donating events that occurred at copy number transition points or involved high-level DNA-amplifications. Sequencing of genomic fusion break points confirmed that DNA-level rearrangements underlie selected fusion transcripts. Furthermore, a significant portion (>60%) of the fusion genes were alternatively spliced. This illustrates the importance of reanalyzing sequencing data as gene definitions change and bioinformatic methods improve, and highlights the previously unforeseen isoform diversity among fusion transcripts.

Scroll wave dynamics in a three-dimensional cardiac tissue model: roles of restitution, thickness, and fiber rotation.

PubMed Central

Qu, Z; Kil, J; Xie, F; Garfinkel, A; Weiss, J N

2000-01-01

Scroll wave (vortex) breakup is hypothesized to underlie ventricular fibrillation, the leading cause of sudden cardiac death. We simulated scroll wave behaviors in a three-dimensional cardiac tissue model, using phase I of the Luo-Rudy (LR1) action potential model. The effects of action potential duration (APD) restitution, tissue thickness, filament twist, and fiber rotation were studied. We found that APD restitution is the major determinant of scroll wave behavior and that instabilities arising from APD restitution are the main determinants of scroll wave breakup in this cardiac model. We did not see a "thickness-induced instability" in the LR1 model, but a minimum thickness is required for scroll breakup in the presence of fiber rotation. The major effect of fiber rotation is to maintain twist in a scroll wave, promoting filament bending and thus scroll breakup. In addition, fiber rotation induces curvature in the scroll wave, which weakens conduction and further facilitates wave break. PMID:10827961

Vortex arrays and ciliary tangles underlie the feeding-swimming tradeoff in starfish larvae

NASA Astrophysics Data System (ADS)

Gilpin, William; Prakash, Vivek N.; Prakash, Manu

2016-11-01

Many marine invertebrates have larval stages covered in linear arrays of beating cilia, which propel the animal while simultaneously entraining planktonic prey. These bands are strongly conserved across taxa spanning four major superphyla, and they are responsible for the unusual morphologies of many invertebrates. However, few studies have investigated their underlying hydrodynamics. Here, we study the ciliary bands of starfish larvae, and discover a beautiful pattern of slowly-evolving vortices that surrounds the swimming animals. Closer inspection of the bands reveals unusual ciliary "tangles" analogous to topological defects that break-up and re-form as the animal adjusts its swimming stroke. Quantitative experiments and modeling demonstrate that these vortices create a physical tradeoff between feeding and swimming in heterogenous environments, which manifests as distinct flow patterns or "eigenstrokes" representing each behavior-potentially implicating neuronal control of cilia. This quantitative interplay between larval form and hydrodynamic function generalizes to other invertebrates, and illustrates the potential effects of active boundary conditions in other biological and synthetic systems.

Therapeutic genome engineering via CRISPR-Cas systems.

PubMed

Moreno, Ana M; Mali, Prashant

2017-07-01

Differences in genomes underlie most organismal diversity, and aberrations in genomes underlie many disease states. With the growing knowledge of the genetic and pathogenic basis of human disease, development of safe and efficient platforms for genome and epigenome engineering will transform our ability to therapeutically target human diseases and also potentially engineer disease resistance. In this regard, the recent advent of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) RNA-guided nuclease systems have transformed our ability to target nucleic acids. Here we review therapeutic genome engineering applications with a specific focus on the CRISPR-Cas toolsets. We summarize past and current work, and also outline key challenges and future directions. WIREs Syst Biol Med 2017, 9:e1380. doi: 10.1002/wsbm.1380 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Sensorimotor simulations underlie conceptual representations: modality-specific effects of prior activation.

PubMed

Pecher, Diane; Zeelenberg, René; Barsalou, Lawrence W

2004-02-01

According to the perceptual symbols theory (Barsalou, 1999), sensorimotor simulations underlie the representation of concepts. Simulations are componential in the sense that they vary with the context in which the concept is presented. In the present study, we investigated whether representations are affected by recent experiences with a concept. Concept names (e.g., APPLE) were presented twice in a property verification task with a different property on each occasion. The two properties were either from the same perceptual modality (e.g., green, shiny) or from different modalities (e.g., tart, shiny). All stimuli were words. There was a lag of several intervening trials between the first and second presentation. Verification times and error rates for the second presentation of the concept were higher if the properties were from different modalities than if they were from the same modality.

Validation and Comparison of Accelerometers Worn on the Hip, Thigh, and Wrists for Measuring Physical Activity and Sedentary Behavior.

PubMed

Montoye, Alexander H K; Pivarnik, James M; Mudd, Lanay M; Biswas, Subir; Pfeiffer, Karin A

2016-01-01

Recent evidence suggests that physical activity (PA) and sedentary behavior (SB) exert independent effects on health. Therefore, measurement methods that can accurately assess both constructs are needed. To compare the accuracy of accelerometers placed on the hip, thigh, and wrists, coupled with machine learning models, for measurement of PA intensity category (SB, light-intensity PA [LPA], and moderate- to vigorous-intensity PA [MVPA]) and breaks in SB. Forty young adults (21 female; age 22.0 ± 4.2 years) participated in a 90-minute semi-structured protocol, performing 13 activities (three sedentary, 10 non-sedentary) for 3-10 minutes each. Participants chose activity order, duration, and intensity. Direct observation (DO) was used as a criterion measure of PA intensity category, and transitions from SB to a non-sedentary activity were breaks in SB. Participants wore four accelerometers (right hip, right thigh, and both wrists), and a machine learning model was created for each accelerometer to predict PA intensity category. Sensitivity and specificity for PA intensity category classification were calculated and compared across accelerometers using repeated measures analysis of variance, and the number of breaks in SB was compared using repeated measures analysis of variance. Sensitivity and specificity values for the thigh-worn accelerometer were higher than for wrist- or hip-worn accelerometers, > 99% for all PA intensity categories. Sensitivity and specificity for the hip-worn accelerometer were 87-95% and 93-97%. The left wrist-worn accelerometer had sensitivities and specificities of > 97% for SB and LPA and 91-95% for MVPA, whereas the right wrist-worn accelerometer had sensitivities and specificities of 93-99% for SB and LPA but 67-84% for MVPA. The thigh-worn accelerometer had high accuracy for breaks in SB; all other accelerometers overestimated breaks in SB. Coupled with machine learning modeling, the thigh-worn accelerometer should be considered when objectively assessing PA and SB.

Epigenetic events underlie the pathogenesis of sinonasal papillomas.

PubMed

Stephen, Josena K; Vaught, Lori E; Chen, Kang M; Sethi, Seema; Shah, Veena; Benninger, Michael S; Gardner, Glendon M; Schweitzer, Vanessa G; Khan, Mumtaz; Worsham, Maria J

2007-10-01

Benign inverted papillomas have been reported as monoclonal but lacking common genetic alterations identified in squamous cell carcinoma of the head and neck. Epigenetic changes alter the heritable state of gene expression and chromatin organization without change in DNA sequence. We investigated whether epigenetic events of aberrant promoter hypermethylation in genes known to be involved in squamous head and neck cancer underlie the pathogenesis of sinonasal papillomas. Ten formalin-fixed paraffin DNA samples from three inverted papilloma cases, two exophytic (everted) papilloma cases, and two cases with inverted and exophytic components were studied. DNA was obtained from microdissected areas of normal and papilloma areas and examined using a panel of 41 gene probes, designed to interrogate 35 unique genes for aberrant methylation status (22 genes) using the methylation-specific multiplex-ligation-specific polymerase assay. Methylation-specific PCR was employed to confirm aberrant methylation detected by the methylation-specific multiplex-ligation-specific polymerase assay. All seven cases indicated at least one epigenetic event of aberrant promoter hypermethylation. The CDKN2B gene was a consistent target of aberrant methylation in six of seven cases. Methylation-specific PCR confirmed hypermethylation of CDKN2B. Recurrent biopsies from two inverted papilloma cases had common epigenetic events. Promoter hypermethylation of CDKN2B was a consistent epigenetic event. Common epigenetic alterations in recurrent biopsies underscore a monoclonal origin for these lesions. Epigenetic events contribute to the underlying pathogenesis of benign inverted and exophytic papillomas. As a consistent target of aberrant promoter hypermethylation, CDKN2B may serve as an important epigenetic biomarker for gene reactivation studies.

Applying Prevention and Positive Youth Development Theory to Predict Depressive Symptoms among Young People

ERIC Educational Resources Information Center

Olson, Jonathan R.; Goddard, H. Wallace

2015-01-01

The purpose of this study was to identify predictors of depressive symptoms among adolescents using concepts drawn from two theoretical models that underlie popular youth-focused programs. Specifically, we assessed the degree to which family-level risk factors increase the likelihood of depressive symptoms, and the degree to which community and/or…

Using Focus Groups to Study ALN Faculty Motivation

ERIC Educational Resources Information Center

Hiltz, Starr Roxanne; Shea, Peter; Kim, Eunhee

2007-01-01

What are the most significant factors that motivate and inhibit faculty with regard to teaching in online environments? And what are the specific kinds of experiences that underlie and explain the importance of these factors? One goal of this study was to add to understanding of these issues, but the primary purpose of this study is determining…

Using Focus Groups to Study ALN Faculty Motivation

ERIC Educational Resources Information Center

Hiltz, Starr Roxanne; Shea, Peter; Kim, Eunhee

2010-01-01

What are the most significant factors that motivate and inhibit faculty with regard to teaching in online environments? And what are the specific kinds of experiences that underlie and explain the importance of these factors? One goal of this study was to add to understanding of these issues, but the primary purpose of this study is determining…

Remembering Kinds: New Evidence that Categories are Privileged in Children's Thinking

ERIC Educational Resources Information Center

Cimpian, Andrei; Erickson, Lucy C.

2012-01-01

What are the representations and learning mechanisms that underlie conceptual development? The present research provides evidence in favor of the claim that this process is guided by an early-emerging predisposition to think and learn about abstract kinds. Specifically, three studies (N=192) demonstrated that 4- to 7-year-old children have better…

Moderation of Cognitive-Achievement Relations for Children with Specific Learning Disabilities: A Multi-Group Latent Variable Analysis Using CHC Theory

ERIC Educational Resources Information Center

Niileksela, Christopher R.

2012-01-01

Recent advances in the understanding of the relations between cognitive abilities and academic skills have helped shape a better understanding of which cognitive processes may underlie different types of SLD (Flanagan, Fiorello, & Ortiz, 2010). Similarities and differences in cognitive-achievement relations for children with and without SLDs…

Families of phosphoinositide-specific phospholipase C: structure and function.

PubMed

Katan, M

1998-12-08

A large number of extracellular signals stimulate hydrolysis of phosphatidylinositol 4,5-bisphosphate by phosphoinositide-specific phospholipase C (PI-PLC). PI-PLC isozymes have been found in a broad spectrum of organisms and although they have common catalytic properties, their regulation involves different signalling pathways. A number of recent studies provided an insight into domain organisation of PI-PLC isozymes and contributed towards better understanding of the structural basis for catalysis, cellular localisation and molecular changes that could underlie the process of their activation.

Analysis of unrejoined chromosomal breakage in human fibroblast cells exposed to low- and high-LET radiation

NASA Technical Reports Server (NTRS)

Wu, Honglu; Furusawa, Yoshiya; George, Kerry; Kawata, Tetsuya; Cucinotta, Francis A.

2002-01-01

Reported studies of DNA breakage induced by radiation of various qualities have generally shown a higher fraction of unrejoined residual breaks after high-LET exposure. This observation is supported by the argument that high-LET radiation induced DNA breaks that are more complex in nature and, thus, less likely to be repaired. In most cases the doses used in these studies were very high. We have studied unrejoined chromosome breaks by analyzing chromosome aberrations using a fluorescence in situ hybridization (FISH) technique with a combination of whole chromosome specific probes and probes specific for the telomere region of the chromosomes. Confluent human fibroblast cells (AG1522) were irradiated with gamma rays, 490 MeV/nucleon Si, or with Fe ions at either 200 and 500 MeV/nucleon, and were allowed to repair at 37 degrees C for 24 hours after exposure. A chemically induced premature chromosome condensation (PCC) technique was used to condense chromosomes in the G2 phase of the cell cycle. Results showed that the frequency of unrejoined chromosome breaks was higher after high-LET radiation, and the ratio of unrejoined to misrejoined chromosome breaks increased steadily with LET up a peak value at 440 keV/microm.

Evidence for non-conservative current-induced forces in the breaking of Au and Pt atomic chains.

PubMed

Sabater, Carlos; Untiedt, Carlos; van Ruitenbeek, Jan M

2015-01-01

This experimental work aims at probing current-induced forces at the atomic scale. Specifically it addresses predictions in recent work regarding the appearance of run-away modes as a result of a combined effect of the non-conservative wind force and a 'Berry force'. The systems we consider here are atomic chains of Au and Pt atoms, for which we investigate the distribution of break down voltage values. We observe two distinct modes of breaking for Au atomic chains. The breaking at high voltage appears to behave as expected for regular break down by thermal excitation due to Joule heating. However, there is a low-voltage breaking mode that has characteristics expected for the mechanism of current-induced forces. Although a full comparison would require more detailed information on the individual atomic configurations, the systems we consider are very similar to those considered in recent model calculations and the comparison between experiment and theory is very encouraging for the interpretation we propose.

Evidence for non-conservative current-induced forces in the breaking of Au and Pt atomic chains

PubMed Central

Sabater, Carlos; Untiedt, Carlos

2015-01-01

Summary This experimental work aims at probing current-induced forces at the atomic scale. Specifically it addresses predictions in recent work regarding the appearance of run-away modes as a result of a combined effect of the non-conservative wind force and a ‘Berry force’. The systems we consider here are atomic chains of Au and Pt atoms, for which we investigate the distribution of break down voltage values. We observe two distinct modes of breaking for Au atomic chains. The breaking at high voltage appears to behave as expected for regular break down by thermal excitation due to Joule heating. However, there is a low-voltage breaking mode that has characteristics expected for the mechanism of current-induced forces. Although a full comparison would require more detailed information on the individual atomic configurations, the systems we consider are very similar to those considered in recent model calculations and the comparison between experiment and theory is very encouraging for the interpretation we propose. PMID:26734525

Callous-unemotional traits and empathy deficits: Mediating effects of affective perspective-taking and facial emotion recognition.

PubMed

Lui, Joyce H L; Barry, Christopher T; Sacco, Donald F

2016-09-01

Although empathy deficits are thought to be associated with callous-unemotional (CU) traits, findings remain equivocal and little is known about what specific abilities may underlie these purported deficits. Affective perspective-taking (APT) and facial emotion recognition may be implicated, given their independent associations with both empathy and CU traits. The current study examined how CU traits relate to cognitive and affective empathy and whether APT and facial emotion recognition mediate these relations. Participants were 103 adolescents (70 males) aged 16-18 attending a residential programme. CU traits were negatively associated with cognitive and affective empathy to a similar degree. The association between CU traits and affective empathy was partially mediated by APT. Results suggest that assessing mechanisms that may underlie empathic deficits, such as perspective-taking, may be important for youth with CU traits and may inform targets of intervention.

Traces of Lorentz symmetry breaking in a hydrogen atom at ground state

NASA Astrophysics Data System (ADS)

Borges, L. H. C.; Barone, F. A.

2016-02-01

Some traces of a specific Lorentz symmetry breaking scenario in the ground state of the hydrogen atom are investigated. We use standard Rayleigh-Schrödinger perturbation theory in order to obtain the corrections to the ground state energy and the wave function. It is shown that an induced four-pole moment arises, due to the Lorentz symmetry breaking. The model considered is the one studied in Borges et al. (Eur Phys J C 74:2937, 2014), where the Lorentz symmetry is broken in the electromagnetic sector.

Electrophysiological Evidence for the Influence of Unitization on the Processes Engaged During Episodic Retrieval: Enhancing Familiarity Based Remembering

ERIC Educational Resources Information Center

Rhodes, Sinead M.; Donaldson, David I.

2007-01-01

Episodic memory depends upon multiple dissociable retrieval processes. Here we investigated the degree to which the processes engaged during successful retrieval are dependent on the properties of the representations that underlie memory for an event. Specifically we examined whether the individual elements of an event can, under some conditions,…

Detection of Q-Matrix Misspecification Using Two Criteria for Validation of Cognitive Structures under the Least Squares Distance Model

ERIC Educational Resources Information Center

Romero, Sonia J.; Ordoñez, Xavier G.; Ponsoda, Vincente; Revuelta, Javier

2014-01-01

Cognitive Diagnostic Models (CDMs) aim to provide information about the degree to which individuals have mastered specific attributes that underlie the success of these individuals on test items. The Q-matrix is a key element in the application of CDMs, because contains links item-attributes representing the cognitive structure proposed for solve…

Significance of multiple neurochemicals that regulate respiration.

PubMed

Pilowsky, Paul M; Sun, Qi-Jian; Lonergan, Tina; Makeham, John M; Seyedabadi, Maryam; Verner, Todd A; Goodchild, Ann K

2008-01-01

Current efforts to characterize the neuronal mechanisms that underlie automatic breathing generally adopt a 'minimalist' approach. In this review, we survey three of the many neurochemicals that are known to be present in raphe neurons and may be involved in respiration. Specifically, we ask the question, 'Is the minimalist approach consistent with the large number of neuronal types and neurochemicals found in respiratory centres'?

Cellular dynamical mechanisms for encoding the time and place of events along spatiotemporal trajectories in episodic memory.

PubMed

Hasselmo, Michael E; Giocomo, Lisa M; Brandon, Mark P; Yoshida, Motoharu

2010-12-31

Understanding the mechanisms of episodic memory requires linking behavioral data and lesion effects to data on the dynamics of cellular membrane potentials and population interactions within brain regions. Linking behavior to specific membrane channels and neurochemicals has implications for therapeutic applications. Lesions of the hippocampus, entorhinal cortex and subcortical nuclei impair episodic memory function in humans and animals, and unit recording data from these regions in behaving animals indicate episodic memory processes. Intracellular recording in these regions demonstrates specific cellular properties including resonance, membrane potential oscillations and bistable persistent spiking that could underlie the encoding and retrieval of episodic trajectories. A model presented here shows how intrinsic dynamical properties of neurons could mediate the encoding of episodic memories as complex spatiotemporal trajectories. The dynamics of neurons allow encoding and retrieval of unique episodic trajectories in multiple continuous dimensions including temporal intervals, personal location, the spatial coordinates and sensory features of perceived objects and generated actions, and associations between these elements. The model also addresses how cellular dynamics could underlie unit firing data suggesting mechanisms for coding continuous dimensions of space, time, sensation and action. Copyright © 2010 Elsevier B.V. All rights reserved.

Cellular dynamical mechanisms for encoding the time and place of events along spatiotemporal trajectories in episodic memory

PubMed Central

Hasselmo, Michael E.; Giocomo, Lisa M.; Yoshida, Motoharu

2010-01-01

Understanding the mechanisms of episodic memory requires linking behavioural data and lesion effects to data on the dynamics of cellular membrane potentials and population interactions within these brain regions. Linking behavior to specific membrane channels and neurochemicals has implications for therapeutic applications. Lesions of the hippocampus, entorhinal cortex and subcortical nuclei impair episodic memory function in humans and animals, and unit recording data from these regions in behaving animals indicate episodic memory processes. Intracellular recording in these regions demonstrates specific cellular properties including resonance, membrane potential oscillations and bistable persistent spiking that could underlie the encoding and retrieval of episodic trajectories. A model presented here shows how intrinsic dynamical properties of neurons could mediate the encoding of episodic memories as complex spatiotemporal trajectories. The dynamics of neurons allow encoding and retrieval of unique episodic trajectories in multiple continuous dimensions including temporal intervals, personal location, the spatial coordinates and sensory features of perceived objects and generated actions, and associations between these elements. The model also addresses how cellular dynamics could underlie unit firing data suggesting mechanisms for coding continuous dimensions of space, time, sensation and action. PMID:20018213

Conformer-specific microwave spectroscopy of 3-phenylpropionitrile by strong field coherence breaking

NASA Astrophysics Data System (ADS)

Fritz, Sean M.; Hernandez-Castillo, A. O.; Abeysekera, Chamara; Hays, Brian M.; Zwier, Timothy S.

2018-07-01

Strong field coherence breaking (SFCB) was used with a chirped-pulse Fourier Transform microwave spectrometer to obtain conformer-specific rotational spectra of 3-phenylpropionitrile in the 8-18 GHz region. Transitions belonging to anti and gauche conformers were identified and assigned and accurate experimental rotational constants were determined to provide insight to the molecular structure. Experimental rotational transitions provided relative abundances in the supersonic expansion. A modified line picking scheme was developed in the process to modulate more transitions and improve the overall efficiency of the SFCB multiple selective excitation technique.

Targeting SOD1 induces synthetic lethal killing in BLM- and CHEK2-deficient colorectal cancer cells

PubMed Central

Sajesh, Babu V.; McManus, Kirk J.

2015-01-01

Cancer is a major cause of death throughout the world, and there is a large need for better and more personalized approaches to combat the disease. Over the past decade, synthetic lethal approaches have been developed that are designed to exploit the aberrant molecular origins (i.e. defective genes) that underlie tumorigenesis. BLM and CHEK2 are two evolutionarily conserved genes that are somatically altered in a number of tumor types. Both proteins normally function in preserving genome stability through facilitating the accurate repair of DNA double strand breaks. Thus, uncovering synthetic lethal interactors of BLM and CHEK2 will identify novel candidate drug targets and lead chemical compounds. Here we identify an evolutionarily conserved synthetic lethal interaction between SOD1 and both BLM and CHEK2 in two distinct cell models. Using quantitative imaging microscopy, real-time cellular analyses, colony formation and tumor spheroid models we show that SOD1 silencing and inhibition (ATTM and LCS-1 treatments), or the induction of reactive oxygen species (2ME2 treatment) induces selective killing within BLM- and CHEK2-deficient cells relative to controls. We further show that increases in reactive oxygen species follow SOD1 silencing and inhibition that are associated with the persistence of DNA double strand breaks, and increases in apoptosis. Collectively, these data identify SOD1 as a novel candidate drug target in BLM and CHEK2 cancer contexts, and further suggest that 2ME2, ATTM and LCS-1 are lead therapeutic compounds warranting further pre-clinical study. PMID:26318585

Targeting SOD1 induces synthetic lethal killing in BLM- and CHEK2-deficient colorectal cancer cells.

PubMed

Sajesh, Babu V; McManus, Kirk J

2015-09-29

Cancer is a major cause of death throughout the world, and there is a large need for better and more personalized approaches to combat the disease. Over the past decade, synthetic lethal approaches have been developed that are designed to exploit the aberrant molecular origins (i.e. defective genes) that underlie tumorigenesis. BLM and CHEK2 are two evolutionarily conserved genes that are somatically altered in a number of tumor types. Both proteins normally function in preserving genome stability through facilitating the accurate repair of DNA double strand breaks. Thus, uncovering synthetic lethal interactors of BLM and CHEK2 will identify novel candidate drug targets and lead chemical compounds. Here we identify an evolutionarily conserved synthetic lethal interaction between SOD1 and both BLM and CHEK2 in two distinct cell models. Using quantitative imaging microscopy, real-time cellular analyses, colony formation and tumor spheroid models we show that SOD1 silencing and inhibition (ATTM and LCS-1 treatments), or the induction of reactive oxygen species (2ME2 treatment) induces selective killing within BLM- and CHEK2-deficient cells relative to controls. We further show that increases in reactive oxygen species follow SOD1 silencing and inhibition that are associated with the persistence of DNA double strand breaks, and increases in apoptosis. Collectively, these data identify SOD1 as a novel candidate drug target in BLM and CHEK2 cancer contexts, and further suggest that 2ME2, ATTM and LCS-1 are lead therapeutic compounds warranting further pre-clinical study.

Effect of vacuum arc cathode spot distribution on breaking capacity of the arc-extinguishing chamber

NASA Astrophysics Data System (ADS)

Ding, Can; Yuan, Zhao; He, Junjia

2017-10-01

A DC circuit breaker performs a key function in breaking an intermediate-frequency (IF) current since breaking a pure IF current is equivalent to breaking a very small DC with a reverse IF current. In this study, it is found that cathode spots show a ring-shaped distribution at 2000 Hz. An arc with an uneven distribution of cathode spots has been simulated. The simulation results show that the distribution of cathode spots significantly affect the microparameter distribution of arc plasma. The current distribution on the anode side differs from that on the cathode side under the total radial electric field. Specifically, the anode current distribution is both uneven and concentrated. The applied axial magnetic field, which cannot reduce the concentrated anode current distribution effectively, might increase the concentration of the anode current. Finally, the uneven distribution of cathode spots reduces the breaking capacity of the arc-extinguishing chamber.

[Breaking bad news in oncology: the Belgian experience].

PubMed

Delevallez, F; Lienard, A; Gibon, A-S; Razavi, D

2014-10-01

Breaking bad news is a complex and frequent clinical task for physicians working in oncology. It can have a negative impact on patients and their relatives who are often present during breaking bad news consultations. Many factors influence how the delivery of bad news will be experienced especially the communication skills used by physicians. A three-phase process (post-delivery phase, delivery phase, pre-delivery phase) has been developed to help physician to handle this task more effectively. Communication skills and specific breaking bad news training programs are both necessary and effective. A recent study conducted in Belgium has shown their impact on the time allocated to each of the three phases of this process, on the communication skills used, on the inclusion of the relative in the consultation and on physicians' physiological arousal. These results underscore the importance of promoting intensive communication skills and breaking bad news training programs for health care professionals.

Protective effects of buckwheat honey on DNA damage induced by hydroxyl radicals.

PubMed

Zhou, Juan; Li, Peng; Cheng, Ni; Gao, Hui; Wang, Bini; Wei, Yahui; Cao, Wei

2012-08-01

To understand the antioxidant properties of buckwheat honeys, we investigated their antioxidant effects on hydroxyl radical-induced DNA breaks in the non-site-specific and site-specific systems, the physicochemical properties, antioxidant activities (1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical scavenging activity, chelating, and reducing power assays), total phenolic content and individual phenolic acids were also determined. Total phenolic content of buckwheat honeys ranged from 774 to 1694 mg PA/kg, and p-hydroxybenzoic and p-coumaric acids proved to be the main components in buckwheat honeys. All the buckwheat honey samples possess stronger capability to protect DNA in the non-site-specific systems than in the site-specific systems from being damaged by hydroxyl radicals. In the non-site-specific and site-specific system, buckwheat honeys samples prevented ()OH-induced DNA breaks by 21-78% and 5-31% over control value, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Site- and strand-specific nicking of DNA by fusion proteins derived from MutH and I-SceI or TALE repeats.

PubMed

Gabsalilow, Lilia; Schierling, Benno; Friedhoff, Peter; Pingoud, Alfred; Wende, Wolfgang

2013-04-01

Targeted genome engineering requires nucleases that introduce a highly specific double-strand break in the genome that is either processed by homology-directed repair in the presence of a homologous repair template or by non-homologous end-joining (NHEJ) that usually results in insertions or deletions. The error-prone NHEJ can be efficiently suppressed by 'nickases' that produce a single-strand break rather than a double-strand break. Highly specific nickases have been produced by engineering of homing endonucleases and more recently by modifying zinc finger nucleases (ZFNs) composed of a zinc finger array and the catalytic domain of the restriction endonuclease FokI. These ZF-nickases work as heterodimers in which one subunit has a catalytically inactive FokI domain. We present two different approaches to engineer highly specific nickases; both rely on the sequence-specific nicking activity of the DNA mismatch repair endonuclease MutH which we fused to a DNA-binding module, either a catalytically inactive variant of the homing endonuclease I-SceI or the DNA-binding domain of the TALE protein AvrBs4. The fusion proteins nick strand specifically a bipartite recognition sequence consisting of the MutH and the I-SceI or TALE recognition sequences, respectively, with a more than 1000-fold preference over a stand-alone MutH site. TALE-MutH is a programmable nickase.

Genotoxic assessment in peripheral blood lymphocytes of post-polio individuals using sister chromatid exchange analysis and micronucleus assay.

PubMed

Bhattacharya, Saurabh Kumar; Saraswathy, Radha; Sivakumar, E

2011-07-01

Environmental pollution is a complex issue because of the diversity of anthropogenic agents, both chemical and physical, that have been detected and catalogued. The consequences to biota from exposure to genotoxic agents present an additional problem because of the potential for these agents to produce adverse change at the cellular and organism levels. Past studies in virus have focused on structural damage to the DNA of environmental species that may occur after exposure to genotoxic agents and the use of this information to document exposure and to monitor remediation. In an effort to predict effects at the population, community and ecosystem levels, in the present study, we attempt to characterize damage occurring through genotoxic agents like 5-bromo-2-deoxyuridine, BrdU, using sister chromatid exchange technique and the formation of micronuclei (MN) in the peripheral lymphocytes of the post-polio syndrome sequelae affected by poliovirus. Analysis of structural chromosomal aberrations (CAs) and involvement of the specific chromosome break were pursued in this study. They revealed a significantly higher incidence of CAs (chromatid and chromosome breaks) in patients compared with controls, where the specific chromosome break has emerged as specific. Also, the maximum numbers of breaks were found to be in chromosome 1 at the position 1p36.1. The results also suggest a correlation between CAs and content of MN.

Histone H3 and the histone acetyltransferase Hat1p contribute to DNA double-strand break repair.

PubMed

Qin, Song; Parthun, Mark R

2002-12-01

The modification of newly synthesized histones H3 and H4 by type B histone acetyltransferases has been proposed to play a role in the process of chromatin assembly. The type B histone acetyltransferase Hat1p and specific lysine residues in the histone H3 NH(2)-terminal tail (primarily lysine 14) are redundantly required for telomeric silencing. As many gene products, including other factors involved in chromatin assembly, have been found to participate in both telomeric silencing and DNA damage repair, we tested whether mutations in HAT1 and the histone H3 tail were also sensitive to DNA-damaging agents. Indeed, mutations both in specific lysine residues in the histone H3 tail and in HAT1 resulted in sensitivity to methyl methanesulfonate. The DNA damage sensitivity of the histone H3 and HAT1 mutants was specific for DNA double-strand breaks, as these mutants were sensitive to the induction of an exogenous restriction endonuclease, EcoRI, but not to UV irradiation. While histone H3 mutations had minor effects on nonhomologous end joining, the primary defect in the histone H3 and HAT1 mutants was in the recombinational repair of DNA double-strand breaks. Epistasis analysis indicates that the histone H3 and HAT1 mutants may influence DNA double-strand break repair through Asf1p-dependent chromatin assembly.

Colorimetric detection of UV light-induced single-strand DNA breaks using gold nanoparticles.

PubMed

Kim, Joong Hyun; Chung, Chan Ho; Chung, Bong Hyun

2013-02-21

We developed a colorimetric method to specifically detect single-strand DNA breaks using gold nanoparticles. In our assay, broken DNA cannot stabilize gold nanoparticles to prevent salt-induced aggregation as good as intact DNA can, and this effect can be easily observed with the naked eye as a red-to-purple color change.

75 FR 8139 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses Involving No...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-23

... the large break loss-of-coolant accident (LOCA) analysis methodology with a reference to WCAP-16009-P... required by 10 CFR 50.91(a), the licensee has provided its analysis of the issue of no significant hazards... Section 5.6.5 to incorporate a new large break LOCA analysis methodology. Specifically, the proposed...

49 CFR 178.345-8 - Accident damage protection.

Code of Federal Regulations, 2011 CFR

2011-10-01

... accidental loss of lading. The device must break at no more than 70 percent of the load that would be... major radius of the tank shell. The device must break at no more than 70 percent of the load that would... requirements of this section and the applicable individual specification to minimize the potential for the loss...

49 CFR 178.345-8 - Accident damage protection.

Code of Federal Regulations, 2013 CFR

2013-10-01

... accidental loss of lading. The device must break at no more than 70 percent of the load that would be... major radius of the tank shell. The device must break at no more than 70 percent of the load that would... requirements of this section and the applicable individual specification to minimize the potential for the loss...

49 CFR 178.345-8 - Accident damage protection.

Code of Federal Regulations, 2014 CFR

2014-10-01

... accidental loss of lading. The device must break at no more than 70 percent of the load that would be... major radius of the tank shell. The device must break at no more than 70 percent of the load that would... requirements of this section and the applicable individual specification to minimize the potential for the loss...

49 CFR 178.345-8 - Accident damage protection.

Code of Federal Regulations, 2012 CFR

2012-10-01

... accidental loss of lading. The device must break at no more than 70 percent of the load that would be... major radius of the tank shell. The device must break at no more than 70 percent of the load that would... requirements of this section and the applicable individual specification to minimize the potential for the loss...

Break-even analysis of Medicaid vs fee for service in orthodontic practice: North Carolina as a case study.

PubMed

Murdock, John E; Phillips, Ceib; Beane, Richard; Quinonez, Rocio

2010-03-01

Access to orthodontic services for children enrolled in Medicaid is limited nationwide. Orthodontists cite low fee reimbursement as a significant barrier to Medicaid participation. The purpose of this study was to examine, under a specific set of practice assumptions, the simulated effect on profitability of treating patients covered by Medicaid in orthodontic practices in North Carolina by using a break-even analysis for the 2005 fiscal year. Questionnaires were mailed to 154 orthodontists in active practice in North Carolina. The response rate was 58%. Seventy respondents met the eligibility criteria. Respondents were categorized into 4 groups based on the number of 2005 Medicaid case starts (I, 0; II, 1-5; III, 6-12; IV, 13 or more). By using the aggregated responses for treatment fees, treatment times, and overhead percentages for each group, average per-patient costs were calculated for each group and used in a break-even analysis. Group I accounted for 60% of respondents; group II, 20%; group III, 9%; and group IV, 11%. Assuming that the break-even point had not been reached, the group I practice would have an average estimated loss of $164 per patient whereas groups II, III, and IV would realize average profits from $98 to $256. The break-even point increased slightly in groups I, II, and III after the total number of patients in the patient pool was increased by 5%, assuming that additional patients were enrolled in Medicaid: group I, 203 to 210; group II, 220 to 226; group III, 158 to 160. The break-even point for group IV was 234 patients. Assuming that the break-even point had been reached, all groups were estimated to realize average per-patient profits of $1483 to $1897. Break-even analysis is a basic economic concept applicable to orthodontic practices. Under the specific conditions of this study, the inclusion of 5% of patients enrolled in Medicaid in the active patient pool had minimal effect on the financial break-even point and, assuming that the break-even point had been reached, was unlikely to have a negative financial impact on the practice. 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Limitations associated with managing chronic low back pain.

PubMed

Beland, Paul

2016-04-20

Non-specific chronic low back pain is an occupational hazard for nurses. It may result in persistent and disabling pain for some people. There are many techniques for investigating, assessing and treating chronic low back pain. However, research to support some of these interventions and the assumptions that underlie them is limited. Interventions that may be beneficial are not always available to those who need them. Changes to service provision are required to rectify this situation and provide effective treatment for patients with non-specific chronic low back pain.

Determination and analysis of site-specific 125I decay-induced DNA double-strand break end-group structures.

PubMed

Datta, Kamal; Weinfeld, Michael; Neumann, Ronald D; Winters, Thomas A

2007-02-01

End groups contribute to the structural complexity of radiation-induced DNA double-strand breaks (DSBs). As such, end-group structures may affect a cell's ability to repair DSBs. The 3'-end groups of strand breaks caused by gamma radiation, or oxidative processes, under oxygenated aqueous conditions have been shown to be distributed primarily between 3'-phosphoglycolate and 3'-phosphate, with 5'-phosphate ends in both cases. In this study, end groups of the high-LET-like DSBs caused by 125I decay were investigated. Site-specific DNA double-strand breaks were produced in plasmid pTC27 in the presence or absence of 2 M DMSO by 125I-labeled triplex-forming oligonucleotide targeting. End-group structure was assessed enzymatically as a function of the DSB end to serve as a substrate for ligation and various forms of end labeling. Using this approach, we have demonstrated 3'-hydroxyl (3'-OH) and 3'-phosphate (3'-P) end groups and 5'-ends (> or = 42%) terminated by phosphate. A 32P postlabeling assay failed to detect 3'-phosphoglycolate in a restriction fragment terminated by the 125I-induced DNA double-strand break, and this is likely due to restricted oxygen diffusion during irradiation as a frozen aqueous solution. Even so, end-group structure and relative distribution varied as a function of the free radical scavenging capacity of the irradiation buffer.

Evaluation of two videotape instruction programmes on how to break bad news--for Cantonese-speaking medical students in Hong Kong.

PubMed

Betson, C L; Fielding, R; Wong, G; Chung, S F; Nestel, D F

1997-12-01

To evaluate a culture-specific videotape on how to 'break bad news' and another videotape produced by a western university, and to determine if the language of presentation influenced the students' perceived abilities to execute basic skills. Third year medical students at the Faculty of Medicine, the University of Hong Kong. Longitudinal study with experimental design. Two instructional tapes on breaking bad news; one using Chinese speaking role models and one using English. In both groups, self-efficacy summed scores increased from 26.8 (95% CI = 25.9-27.7) at the pre-test to 29.0 (95% CI = 28.4-29.6). The biggest changes occurred in perceived self-efficacy regarding specific skills. However, students using the Chinese tape rated skills as more useful than those using the English tape. The videotapes were useful in teaching communication skills. Culturally relevant audiovisual materials were more effective.

Nuclear ARP2/3 drives DNA break clustering for homology-directed repair.

PubMed

Schrank, Benjamin R; Aparicio, Tomas; Li, Yinyin; Chang, Wakam; Chait, Brian T; Gundersen, Gregg G; Gottesman, Max E; Gautier, Jean

2018-06-20

DNA double-strand breaks repaired by non-homologous end joining display limited DNA end-processing and chromosomal mobility. By contrast, double-strand breaks undergoing homology-directed repair exhibit extensive processing and enhanced motion. The molecular basis of this movement is unknown. Here, using Xenopus laevis cell-free extracts and mammalian cells, we establish that nuclear actin, WASP, and the actin-nucleating ARP2/3 complex are recruited to damaged chromatin undergoing homology-directed repair. We demonstrate that nuclear actin polymerization is required for the migration of a subset of double-strand breaks into discrete sub-nuclear clusters. Actin-driven movements specifically affect double-strand breaks repaired by homology-directed repair in G2 cell cycle phase; inhibition of actin nucleation impairs DNA end-processing and homology-directed repair. By contrast, ARP2/3 is not enriched at double-strand breaks repaired by non-homologous end joining and does not regulate non-homologous end joining. Our findings establish that nuclear actin-based mobility shapes chromatin organization by generating repair domains that are essential for homology-directed repair in eukaryotic cells.

Indicator saturation: a novel approach to detect multiple breaks in geodetic time series.

NASA Astrophysics Data System (ADS)

Jackson, L. P.; Pretis, F.; Williams, S. D. P.

2016-12-01

Geodetic time series can record long term trends, quasi-periodic signals at a variety of time scales from days to decades, and sudden breaks due to natural or anthropogenic causes. The causes of breaks range from instrument replacement to earthquakes to unknown (i.e. no attributable cause). Furthermore, breaks can be permanent or short-lived and range at least two orders of magnitude in size (mm to 100's mm). To account for this range of possible signal-characteristics requires a flexible time series method that can distinguish between true and false breaks, outliers and time-varying trends. One such method, Indicator Saturation (IS) comes from the field of econometrics where analysing stochastic signals in these terms is a common problem. The IS approach differs from alternative break detection methods by considering every point in the time series as a break until it is demonstrated statistically that it is not. A linear model is constructed with a break function at every point in time, and all but statistically significant breaks are removed through a general-to-specific model selection algorithm for more variables than observations. The IS method is flexible because it allows multiple breaks of different forms (e.g. impulses, shifts in the mean, and changing trends) to be detected, while simultaneously modelling any underlying variation driven by additional covariates. We apply the IS method to identify breaks in a suite of synthetic GPS time series used for the Detection of Offsets in GPS Experiments (DOGEX). We optimise the method to maximise the ratio of true-positive to false-positive detections, which improves estimates of errors in the long term rates of land motion currently required by the GPS community.

Alternative Break Programs and the Factors that Contribute to Changes in Students' Lives

ERIC Educational Resources Information Center

Niehaus, Elizabeth Kathleen

2012-01-01

The purpose of this study was to explore the extent to and ways in which student participants in Alternative Break (AB) programs report that their AB experience influenced their intentions or plans to volunteer, engage in advocacy, or study or travel abroad, or their major or career plans. Additional analysis explored the specific program…

Colour break in reverse bicolour daffodils is associated with the presence of Narcissus mosaic virus

PubMed Central

2011-01-01

Background Daffodils (Narcissus pseudonarcissus) are one of the world's most popular ornamentals. They also provide a scientific model for studying the carotenoid pigments responsible for their yellow and orange flower colours. In reverse bicolour daffodils, the yellow flower trumpet fades to white with age. The flowers of this type of daffodil are particularly prone to colour break whereby, upon opening, the yellow colour of the perianth is observed to be 'broken' into patches of white. This colour break symptom is characteristic of potyviral infections in other ornamentals such as tulips whose colour break is due to alterations in the presence of anthocyanins. However, reverse bicolour flowers displaying colour break show no other virus-like symptoms such as leaf mottling or plant stunting, leading some to argue that the carotenoid-based colour breaking in reverse bicolour flowers may not be caused by virus infection. Results Although potyviruses have been reported to cause colour break in other flower species, enzyme-linked-immunoassays with an antibody specific to the potyviral family showed that potyviruses were not responsible for the occurrence of colour break in reverse bicolour daffodils. Colour break in this type of daffodil was clearly associated with the presence of large quantities of rod-shaped viral particles of lengths 502-580 nm in tepals. Sap from flowers displaying colour break caused red necrotic lesions on Gomphrena globosa, suggesting the presence of potexvirus. Red necrotic lesions were not observed in this indicator plant when sap from reverse bicolour flowers not showing colour break was used. The reverse transcriptase polymerase reactions using degenerate primers to carla-, potex- and poty-viruses linked viral RNA with colour break and sequencing of the amplified products indicated that the potexvirus Narcissisus mosaic virus was the predominant virus associated with the occurrence of the colour break. Conclusions High viral counts were associated with the reverse bicolour daffodil flowers that were displaying colour break but otherwise showed no other symptoms of infection. Narcissus mosaic virus was the virus that was clearly linked to the carotenoid-based colour break. PMID:21854646

Hard Break-Up of Two-Nucleons and QCD Dynamics of NN Interaction

NASA Astrophysics Data System (ADS)

Sargsian, Misak; Granados, Carlos

2009-05-01

We investigate hard photodisintegration of two nucleons from ^3He nucleus within the framework of hard rescattering model (HRM). In HRM a quark of one nucleon knocked-out by incoming photon rescatters with a quark of the other nucleon leading to the production of two nucleons with high relative momentum. HRM allows to express the amplitude of two-nucleon break-up reaction through the convolution of photon-quark scattering, NN hard scattering amplitude and nuclear spectral function which can be calculated using nonrelativistic ^3He wave function. HRM predicts several specific features for hard break-up reaction. First, the cross section will approximately scale as s-11. Also one predicts comparable or larger cross section for pp break up as compared to that of pn break-up, which is opposite to what is observed in low energy kinematics. Another result is the prediction of different spectator momentum dependencies of pp and pn break-up cross sections. This is due to the fact that same-helicity pp-component is strongly suppressed in the ground state wave function of ^3He. Due to this suppression HRM predicts significantly different asymmetries for the cross section of polarization transfer NN break-up reactions for circularly polarized photons. For the pp break-up this asymmetry is predicted to be zero while for the pn it is close to 23.

Analysis Of Using Firewall And Single Honeypot In Training Attack On Wireless Network

NASA Astrophysics Data System (ADS)

Mohd. Diansyah, Tengku.; Faisal, Ilham; Perdana, Adidtya; Octaviani Sembiring, Boni; Hidayati Sinaga, Tantri

2017-12-01

Security issues become one of the important aspects of a network, especially a network security on the server. These problems underlie the need to build a system that can detect threats from parties who do not have access rights (hackers) that are by building a security system honeypot. A Honeypot is a diversion of intruders' attention, in order for intruders to think that it has managed to break down and retrieve data from a network, when in fact the data is not important and the location is isolated. A way to trap or deny unauthorized use of effort in an information system. One type of honeypot is honeyd. Honeyd is a low interaction honeypot that has a smaller risk compared to high interaction types because the interaction with the honeypot does not directly involve the real system. The purpose of the implementation of honeypot and firewall, firewall is used on Mikrotik. Can be used as an administrative tool to view reports of Honeyd generated activity and administrators can also view reports that are stored in the logs in order to assist in determining network security policies.

A PARP1-ERK2 synergism is required for the induction of LTP

PubMed Central

Visochek, L.; Grigoryan, G.; Kalal, A.; Milshtein-Parush, H.; Gazit, N.; Slutsky, I.; Yeheskel, A.; Shainberg, A.; Castiel, A.; Seger, R.; Langelier, M. F.; Dantzer, F.; Pascal, J. M.; Segal, M.; Cohen-Armon, M.

2016-01-01

Unexpectedly, a post-translational modification of DNA-binding proteins, initiating the cell response to single-strand DNA damage, was also required for long-term memory acquisition in a variety of learning paradigms. Our findings disclose a molecular mechanism based on PARP1-Erk synergism, which may underlie this phenomenon. A stimulation induced PARP1 binding to phosphorylated Erk2 in the chromatin of cerebral neurons caused Erk-induced PARP1 activation, rendering transcription factors and promoters of immediate early genes (IEG) accessible to PARP1-bound phosphorylated Erk2. Thus, Erk-induced PARP1 activation mediated IEG expression implicated in long-term memory. PARP1 inhibition, silencing, or genetic deletion abrogated stimulation-induced Erk-recruitment to IEG promoters, gene expression and LTP generation in hippocampal CA3-CA1-connections. Moreover, a predominant binding of PARP1 to single-strand DNA breaks, occluding its Erk binding sites, suppressed IEG expression and prevented the generation of LTP. These findings outline a PARP1-dependent mechanism required for LTP generation, which may be implicated in long-term memory acquisition and in its deterioration in senescence. PMID:27121568

A PARP1-ERK2 synergism is required for the induction of LTP.

PubMed

Visochek, L; Grigoryan, G; Kalal, A; Milshtein-Parush, H; Gazit, N; Slutsky, I; Yeheskel, A; Shainberg, A; Castiel, A; Seger, R; Langelier, M F; Dantzer, F; Pascal, J M; Segal, M; Cohen-Armon, M

2016-04-28

Unexpectedly, a post-translational modification of DNA-binding proteins, initiating the cell response to single-strand DNA damage, was also required for long-term memory acquisition in a variety of learning paradigms. Our findings disclose a molecular mechanism based on PARP1-Erk synergism, which may underlie this phenomenon. A stimulation induced PARP1 binding to phosphorylated Erk2 in the chromatin of cerebral neurons caused Erk-induced PARP1 activation, rendering transcription factors and promoters of immediate early genes (IEG) accessible to PARP1-bound phosphorylated Erk2. Thus, Erk-induced PARP1 activation mediated IEG expression implicated in long-term memory. PARP1 inhibition, silencing, or genetic deletion abrogated stimulation-induced Erk-recruitment to IEG promoters, gene expression and LTP generation in hippocampal CA3-CA1-connections. Moreover, a predominant binding of PARP1 to single-strand DNA breaks, occluding its Erk binding sites, suppressed IEG expression and prevented the generation of LTP. These findings outline a PARP1-dependent mechanism required for LTP generation, which may be implicated in long-term memory acquisition and in its deterioration in senescence.

The ATM signaling network in development and disease.

PubMed

Stracker, Travis H; Roig, Ignasi; Knobel, Philip A; Marjanović, Marko

2013-01-01

The DNA damage response (DDR) rapidly recognizes DNA lesions and initiates the appropriate cellular programs to maintain genome integrity. This includes the coordination of cell cycle checkpoints, transcription, translation, DNA repair, metabolism, and cell fate decisions, such as apoptosis or senescence (Jackson and Bartek, 2009). DNA double-strand breaks (DSBs) represent one of the most cytotoxic DNA lesions and defects in their metabolism underlie many human hereditary diseases characterized by genomic instability (Stracker and Petrini, 2011; McKinnon, 2012). Patients with hereditary defects in the DDR display defects in development, particularly affecting the central nervous system, the immune system and the germline, as well as aberrant metabolic regulation and cancer predisposition. Central to the DDR to DSBs is the ataxia-telangiectasia mutated (ATM) kinase, a master controller of signal transduction. Understanding how ATM signaling regulates various aspects of the DDR and its roles in vivo is critical for our understanding of human disease, its diagnosis and its treatment. This review will describe the general roles of ATM signaling and highlight some recent advances that have shed light on the diverse roles of ATM and related proteins in human disease.

The ATM signaling network in development and disease

PubMed Central

Stracker, Travis H.; Roig, Ignasi; Knobel, Philip A.; Marjanović, Marko

2013-01-01

The DNA damage response (DDR) rapidly recognizes DNA lesions and initiates the appropriate cellular programs to maintain genome integrity. This includes the coordination of cell cycle checkpoints, transcription, translation, DNA repair, metabolism, and cell fate decisions, such as apoptosis or senescence (Jackson and Bartek, 2009). DNA double-strand breaks (DSBs) represent one of the most cytotoxic DNA lesions and defects in their metabolism underlie many human hereditary diseases characterized by genomic instability (Stracker and Petrini, 2011; McKinnon, 2012). Patients with hereditary defects in the DDR display defects in development, particularly affecting the central nervous system, the immune system and the germline, as well as aberrant metabolic regulation and cancer predisposition. Central to the DDR to DSBs is the ataxia-telangiectasia mutated (ATM) kinase, a master controller of signal transduction. Understanding how ATM signaling regulates various aspects of the DDR and its roles in vivo is critical for our understanding of human disease, its diagnosis and its treatment. This review will describe the general roles of ATM signaling and highlight some recent advances that have shed light on the diverse roles of ATM and related proteins in human disease. PMID:23532176

Vortex arrays and ciliary tangles underlie the feeding-swimming trade-off in starfish larvae

NASA Astrophysics Data System (ADS)

Gilpin, William; Prakash, Vivek N.; Prakash, Manu

2017-04-01

Many marine invertebrates have larval stages covered in linear arrays of beating cilia, which propel the animal while simultaneously entraining planktonic prey. These bands are strongly conserved across taxa spanning four major superphyla, and they are responsible for the unusual morphologies of many invertebrate larvae. However, few studies have investigated their underlying hydrodynamics. Here, we study the ciliary bands of starfish larvae, and discover a beautiful pattern of slowly evolving vortices that surrounds the swimming animals. Closer inspection of the bands reveals unusual ciliary `tangles' analogous to topological defects that break up and re-form as the animal adjusts its swimming stroke. Quantitative experiments and modelling demonstrate that these vortices create a physical trade-off between feeding and swimming in heterogeneous environments, which manifests as distinct flow patterns or `eigenstrokes' representing each behaviour--potentially implicating neuronal control of cilia. This quantitative interplay between larval form and hydrodynamic function may generalize to other invertebrates with ciliary bands, and illustrates the potential effects of active boundary conditions in other biological and synthetic systems.

The Use of Bacterial Repair Endonucleases in the Comet Assay.

PubMed

Collins, Andrew R

2017-01-01

The comet assay is a sensitive electrophoretic method for measuring DNA breaks at the level of single cells, used widely in genotoxicity experiments, in biomonitoring, and in fundamental research. Its sensitivity and range of application are increased by the incorporation of an extra step, after lysis of agarose-embedded cells, in which the DNA is digested with lesion-specific endonucleases (DNA repair enzymes of bacterial or phage origin). Enzymes with specificity for oxidized purines, oxidized pyrimidines, alkylated bases, UV-induced cyclobutane pyrimidine dimers, and misincorporated uracil have been employed. The additional enzyme-sensitive sites, over and above the strand breaks detected in the standard comet assay, give a quantitative estimate of the number of specific lesions present in the cells.

Un formalisme de systemes a sauts pour la recirculation optimale des casses dans une machine a papier

NASA Astrophysics Data System (ADS)

Khanbaghi, Maryam

Increasing closure of white water circuits is making mill productivity and quality of paper produced increasingly affected by the occurrence of paper breaks. In this thesis the main objective is the development of white water and broke recirculation policies. The thesis consists of three main parts, respectively corresponding to the synthesis of a statistical model of paper breaks in a paper mill, the basic mathematical setup for the formulation of white water and broke recirculation policies in the mill as a jump linear quadratic regulation problem, and finally the tuning of the control law based on first passage-time theory, and its extension to the case of control sensitive paper break rates. More specifically, in the first part a statistical model of paper machine breaks is developed. We start from the hypothesis that the breaks process is a Markov chain with three states: the first state is the operational one, while the two others are associated with the general types of paper-breaks that can take place in the mill (wet breaks and dry breaks). The Markovian hypothesis is empirically validated. We also establish how paper-break rates are correlated with machine speed and broke recirculation ratio. Subsequently, we show how the obtained Markov chain model of paper-breaks can be used to formulate a machine operating speed parameter optimization problem. In the second part, upon recognizing that paper breaks can be modelled as a Markov chain type of process which, when interacting with the continuous mill dynamics, yields a jump Markov model, jump linear theory is proposed as a means of constructing white water and broke recirculation strategies which minimize process variability. Reduced process variability comes at the expense of relatively large swings in white water and broke tanks level. Since the linear design does not specifically account for constraints on the state-space, under the resulting law, damaging events of tank overflow or emptiness can occur. A heuristic simulation-based approach is proposed to choose the performance measure design parameters to keep the mean time between incidents of fluid in broke and white water tanks either overflowing, or reaching dangerously low levels, sufficiently long. In the third part, a methodology, mainly founded on the first passage-time theory of stochastic processes, is proposed to choose the performance measure design parameters to limit process variability while accounting for the possibility of undesirable tank overflows or tank emptiness. The heart of the approach is an approximation technique for evaluating mean first passage-times of the controlled tanks levels. This technique appears to have an applicability which largely exceeds the problem area it was designed for. Furthermore, the introduction of control sensitive break rates and the analysis of the ensuing control problem are presented. This is to account for the experimentally observed increase in breaks concomitant with flow rate variability.

Application of Laser Micro-irradiation for Examination of Single and Double Strand Break Repair in Mammalian Cells.

PubMed

Holton, Nathaniel W; Andrews, Joel F; Gassman, Natalie R

2017-09-05

Highly coordinated DNA repair pathways exist to detect, excise and replace damaged DNA bases, and coordinate repair of DNA strand breaks. While molecular biology techniques have clarified structure, enzymatic functions, and kinetics of repair proteins, there is still a need to understand how repair is coordinated within the nucleus. Laser micro-irradiation offers a powerful tool for inducing DNA damage and monitoring the recruitment of repair proteins. Induction of DNA damage by laser micro-irradiation can occur with a range of wavelengths, and users can reliably induce single strand breaks, base lesions and double strand breaks with a range of doses. Here, laser micro-irradiation is used to examine repair of single and double strand breaks induced by two common confocal laser wavelengths, 355 nm and 405 nm. Further, proper characterization of the applied laser dose for inducing specific damage mixtures is described, so users can reproducibly perform laser micro-irradiation data acquisition and analysis.

A study of environmental characterization of conventional and advanced aluminum alloys for selection and design. Phase 2: The breaking load test method

NASA Technical Reports Server (NTRS)

Sprowls, D. O.; Bucci, R. J.; Ponchel, B. M.; Brazill, R. L.; Bretz, P. E.

1984-01-01

A technique is demonstrated for accelerated stress corrosion testing of high strength aluminum alloys. The method offers better precision and shorter exposure times than traditional pass fail procedures. The approach uses data from tension tests performed on replicate groups of smooth specimens after various lengths of exposure to static stress. The breaking strength measures degradation in the test specimen load carrying ability due to the environmental attack. Analysis of breaking load data by extreme value statistics enables the calculation of survival probabilities and a statistically defined threshold stress applicable to the specific test conditions. A fracture mechanics model is given which quantifies depth of attack in the stress corroded specimen by an effective flaw size calculated from the breaking stress and the material strength and fracture toughness properties. Comparisons are made with experimental results from three tempers of 7075 alloy plate tested by the breaking load method and by traditional tests of statistically loaded smooth tension bars and conventional precracked specimens.

Learning new sequential stepping patterns requires striatal plasticity during the earliest phase of acquisition.

PubMed

Nakamura, Toru; Nagata, Masatoshi; Yagi, Takeshi; Graybiel, Ann M; Yamamori, Tetsuo; Kitsukawa, Takashi

2017-04-01

Animals including humans execute motor behavior to reach their goals. For this purpose, they must choose correct strategies according to environmental conditions and shape many parameters of their movements, including their serial order and timing. To investigate the neurobiology underlying such skills, we used a multi-sensor equipped, motor-driven running wheel with adjustable sequences of foothold pegs on which mice ran to obtain water reward. When the peg patterns changed from a familiar pattern to a new pattern, the mice had to learn and implement new locomotor strategies in order to receive reward. We found that the accuracy of stepping and the achievement of water reward improved with the new learning after changes in the peg-pattern, and c-Fos expression levels assayed after the first post-switch session were high in both dorsolateral striatum and motor cortex, relative to post-switch plateau levels. Combined in situ hybridization and immunohistochemistry of striatal sections demonstrated that both enkephalin-positive (indirect pathway) neurons and substance P-positive (direct pathway) neurons were recruited specifically after the pattern switches, as were interneurons expressing neuronal nitric oxide synthase. When we blocked N-methyl-D-aspartate (NMDA) receptors in the dorsolateral striatum by injecting the NMDA receptor antagonist, D-2-amino-5-phosphonopentanoic acid (AP5), we found delays in early post-switch improvement in performance. These findings suggest that the dorsolateral striatum is activated on detecting shifts in environment to adapt motor behavior to the new context via NMDA-dependent plasticity, and that this plasticity may underlie forming and breaking skills and habits as well as to behavioral difficulties in clinical disorders. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Trial Watch

PubMed Central

Aranda, Fernando; Vacchelli, Erika; Eggermont, Alexander; Galon, Jerome; Sautès-Fridman, Catherine; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2013-01-01

Throughout the past 3 decades, along with the recognition that the immune system not only influences oncogenesis and tumor progression, but also determines how established neoplastic lesions respond therapy, renovated enthusiasm has gathered around the possibility of using vaccines as anticancer agents. Such an enthusiasm quickly tempered when it became clear that anticancer vaccines would have to be devised as therapeutic, rather than prophylactic, measures, and that malignant cells often fail to elicit (or actively suppress) innate and adaptive immune responses. Nonetheless, accumulating evidence indicates that a variety of anticancer vaccines, including cell-based, DNA-based, and purified component-based preparations, are capable of circumventing the poorly immunogenic and highly immunosuppressive nature of most tumors and elicit (at least under some circumstances) therapeutically relevant immune responses. Great efforts are currently being devoted to the identification of strategies that may provide anticancer vaccines with the capacity of breaking immunological tolerance and eliciting tumor-associated antigen-specific immunity in a majority of patients. In this sense, promising results have been obtained by combining anticancer vaccines with a relatively varied panels of adjuvants, including multiple immunostimulatory cytokines, Toll-like receptor agonists as well as inhibitors of immune checkpoints. One year ago, in the December issue of OncoImmunology, we discussed the biological mechanisms that underlie the antineoplastic effects of peptide-based vaccines and presented an abundant literature demonstrating the prominent clinical potential of such an approach. Here, we review the latest developments in this exciting area of research, focusing on high-profile studies that have been published during the last 13 mo and clinical trials launched in the same period to evaluate purified peptides or full-length proteins as therapeutic anticancer agents. PMID:24498550

Predicting appointment breaking.

PubMed

Bean, A G; Talaga, J

1995-01-01

The goal of physician referral services is to schedule appointments, but if too many patients fail to show up, the value of the service will be compromised. The authors found that appointment breaking can be predicted by the number of days to the scheduled appointment, the doctor's specialty, and the patient's age and gender. They also offer specific suggestions for modifying the marketing mix to reduce the incidence of no-shows.

Cable yarding residue after thinning young stands: a break-even simulation

Treesearch

Chris B. LeDoux

1984-01-01

The use of cable logging to extract small pieces of residue wood may result in low rates of production and a high cost per unit of wood produced. However, the logging manager can improve yarding productivity and break even in cable residue removal operations by using the proper planning techniques. In this study, breakeven zones for specific young-growth stands were...

Differences in negativity bias probably underlie variation in attitudes toward change generally, not political ideology specifically.

PubMed

Ludeke, Steven G; DeYoung, Colin G

2014-06-01

Many of the characteristics cited in Hibbing et al.'s account are ineffective predictors of economic conservatism. However, these same characteristics are often associated with differences not only in social conservatism but also in religiousness and authoritarianism. Hibbing et al. may have offered a useful explanation of traditionalism and attitudes toward change across domains rather than of general political attitudes.

Quantitative Trait Loci (QTL) that Underlie SCN Resistance in the Soybean [Glycine max (L.) Merr.] ‘PI438489B’ by ‘Hamilton’ Recombinant Inbred Line Population

USDA-ARS?s Scientific Manuscript database

Soybean cyst nematode caused by Heterodera glycines is the most devastating pest in soybean [Glycine max (L.) Merr.]. Resistance to SCN is complex, polygenic, race-cultivar specific, and controlled by several QTL. Our objective was to identify and map QTL for SCN resistance to races 3 and 5 using a ...

Neuroligin-1 links neuronal activity to sleep-wake regulation.

PubMed

El Helou, Janine; Bélanger-Nelson, Erika; Freyburger, Marlène; Dorsaz, Stéphane; Curie, Thomas; La Spada, Francesco; Gaudreault, Pierre-Olivier; Beaumont, Éric; Pouliot, Philippe; Lesage, Frédéric; Frank, Marcos G; Franken, Paul; Mongrain, Valérie

2013-06-11

Maintaining wakefulness is associated with a progressive increase in the need for sleep. This phenomenon has been linked to changes in synaptic function. The synaptic adhesion molecule Neuroligin-1 (NLG1) controls the activity and synaptic localization of N-methyl-d-aspartate receptors, which activity is impaired by prolonged wakefulness. We here highlight that this pathway may underlie both the adverse effects of sleep loss on cognition and the subsequent changes in cortical synchrony. We found that the expression of specific Nlg1 transcript variants is changed by sleep deprivation in three mouse strains. These observations were associated with strain-specific changes in synaptic NLG1 protein content. Importantly, we showed that Nlg1 knockout mice are not able to sustain wakefulness and spend more time in nonrapid eye movement sleep than wild-type mice. These changes occurred with modifications in waking quality as exemplified by low theta/alpha activity during wakefulness and poor preference for social novelty, as well as altered delta synchrony during sleep. Finally, we identified a transcriptional pathway that could underlie the sleep/wake-dependent changes in Nlg1 expression and that involves clock transcription factors. We thus suggest that NLG1 is an element that contributes to the coupling of neuronal activity to sleep/wake regulation.

Motivational "spill-over" during weight control: increased self-determination and exercise intrinsic motivation predict eating self-regulation.

PubMed

Mata, Jutta; Silva, Marlene N; Vieira, Paulo N; Carraça, Eliana V; Andrade, Ana M; Coutinho, Sílvia R; Sardinha, Luis B; Teixeira, Pedro J

2009-11-01

Successful weight management relies on at least two health behaviors, eating and exercise. However, little is known about their interaction on a motivational and behavioral level. Based on the Hierarchical Model of Motivation the authors examined whether exercise-specific motivation can transfer to eating regulation during a lifestyle weight control program. The authors further investigated whether general, treatment-related, and exercise motivation underlie the relation between increased exercise and improved eating regulation. Overweight/obese women participated in a 1-year randomized controlled trial (N = 239). The intervention focused on promoting physical activity and internal motivation for exercise and weight loss, following Self-Determination Theory. The control group received general health education. General and exercise specific self-determination, eating self-regulation variables, and physical activity behavior. General self-determination and more autonomous exercise motivation predicted eating self-regulation over 12 months. Additionally, general and exercise self-determination fully mediated the relation between physical activity and eating self-regulation. Increased general self-determination and exercise motivation seem to facilitate improvements in eating self-regulation during weight control in women. These motivational mechanisms also underlie the relationship between improvements in exercise behavior and eating regulation. PsycINFO Database Record (c) 2009 APA, all rights reserved.

Neuroligin-1 links neuronal activity to sleep-wake regulation

PubMed Central

El Helou, Janine; Bélanger-Nelson, Erika; Freyburger, Marlène; Dorsaz, Stéphane; Curie, Thomas; La Spada, Francesco; Gaudreault, Pierre-Olivier; Beaumont, Éric; Pouliot, Philippe; Lesage, Frédéric; Frank, Marcos G.; Franken, Paul; Mongrain, Valérie

2013-01-01

Maintaining wakefulness is associated with a progressive increase in the need for sleep. This phenomenon has been linked to changes in synaptic function. The synaptic adhesion molecule Neuroligin-1 (NLG1) controls the activity and synaptic localization of N-methyl-d-aspartate receptors, which activity is impaired by prolonged wakefulness. We here highlight that this pathway may underlie both the adverse effects of sleep loss on cognition and the subsequent changes in cortical synchrony. We found that the expression of specific Nlg1 transcript variants is changed by sleep deprivation in three mouse strains. These observations were associated with strain-specific changes in synaptic NLG1 protein content. Importantly, we showed that Nlg1 knockout mice are not able to sustain wakefulness and spend more time in nonrapid eye movement sleep than wild-type mice. These changes occurred with modifications in waking quality as exemplified by low theta/alpha activity during wakefulness and poor preference for social novelty, as well as altered delta synchrony during sleep. Finally, we identified a transcriptional pathway that could underlie the sleep/wake-dependent changes in Nlg1 expression and that involves clock transcription factors. We thus suggest that NLG1 is an element that contributes to the coupling of neuronal activity to sleep/wake regulation. PMID:23716671

Neoplastic cell transformation by high-LET radiation - Molecular mechanisms

NASA Technical Reports Server (NTRS)

Yang, Tracy Chui-Hsu; Craise, Laurie M.; Tobias, Cornelius A.; Mei, Man-Tong

1989-01-01

Quantitative data were collected on dose-response curves of cultured mouse-embryo cells (C3H10T1/2) irradiated with heavy ions of various charges and energies. Results suggests that two breaks formed on DNA within 80 A may cause cell transformation and that two DNA breaks formed within 20 A may be lethal. From results of experiments with restriction enzymes which produce DNA damages at specific sites, it was found that DNA double strand breaks are important primary lesions for radiogenic cell transformation and that blunt-ended double-strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship for high-LET radiation is similar to that for HGPRT locus mutation, chromosomal deletion, and cell transformation, indicating that common lesions may be involved in these radiation effects.

Rapid Long-Range Disynaptic Inhibition Explains the Formation of Cortical Orientation Maps

PubMed Central

Antolík, Ján

2017-01-01

Competitive interactions are believed to underlie many types of cortical processing, ranging from memory formation, attention and development of cortical functional organization (e.g., development of orientation maps in primary visual cortex). In the latter case, the competitive interactions happen along the cortical surface, with local populations of neurons reinforcing each other, while competing with those displaced more distally. This specific configuration of lateral interactions is however in stark contrast with the known properties of the anatomical substrate, i.e., excitatory connections (mediating reinforcement) having longer reach than inhibitory ones (mediating competition). No satisfactory biologically plausible resolution of this conflict between anatomical measures, and assumed cortical function has been proposed. Recently a specific pattern of delays between different types of neurons in cat cortex has been discovered, where direct mono-synaptic excitation has approximately the same delay, as the combined delays of the disynaptic inhibitory interactions between excitatory neurons (i.e., the sum of delays from excitatory to inhibitory and from inhibitory to excitatory neurons). Here we show that this specific pattern of delays represents a biologically plausible explanation for how short-range inhibition can support competitive interactions that underlie the development of orientation maps in primary visual cortex. We demonstrate this statement analytically under simplifying conditions, and subsequently show using network simulations that development of orientation maps is preserved when long-range excitation, direct inhibitory to inhibitory interactions, and moderate inequality in the delays between excitatory and inhibitory pathways is added. PMID:28408869

Co-Option and De Novo Gene Evolution Underlie Molluscan Shell Diversity

PubMed Central

Aguilera, Felipe; McDougall, Carmel

2017-01-01

Abstract Molluscs fabricate shells of incredible diversity and complexity by localized secretions from the dorsal epithelium of the mantle. Although distantly related molluscs express remarkably different secreted gene products, it remains unclear if the evolution of shell structure and pattern is underpinned by the differential co-option of conserved genes or the integration of lineage-specific genes into the mantle regulatory program. To address this, we compare the mantle transcriptomes of 11 bivalves and gastropods of varying relatedness. We find that each species, including four Pinctada (pearl oyster) species that diverged within the last 20 Ma, expresses a unique mantle secretome. Lineage- or species-specific genes comprise a large proportion of each species’ mantle secretome. A majority of these secreted proteins have unique domain architectures that include repetitive, low complexity domains (RLCDs), which evolve rapidly, and have a proclivity to expand, contract and rearrange in the genome. There are also a large number of secretome genes expressed in the mantle that arose before the origin of gastropods and bivalves. Each species expresses a unique set of these more ancient genes consistent with their independent co-option into these mantle gene regulatory networks. From this analysis, we infer lineage-specific secretomes underlie shell diversity, and include both rapidly evolving RLCD-containing proteins, and the continual recruitment and loss of both ancient and recently evolved genes into the periphery of the regulatory network controlling gene expression in the mantle epithelium. PMID:28053006

Individual differences reveal the basis of consonance.

PubMed

McDermott, Josh H; Lehr, Andriana J; Oxenham, Andrew J

2010-06-08

Some combinations of musical notes are consonant (pleasant), whereas others are dissonant (unpleasant), a distinction central to music. Explanations of consonance in terms of acoustics, auditory neuroscience, and enculturation have been debated for centuries. We utilized individual differences to distinguish the candidate theories. We measured preferences for musical chords as well as nonmusical sounds that isolated particular acoustic factors--specifically, the beating and the harmonic relationships between frequency components, two factors that have long been thought to potentially underlie consonance. Listeners preferred stimuli without beats and with harmonic spectra, but across more than 250 subjects, only the preference for harmonic spectra was consistently correlated with preferences for consonant over dissonant chords. Harmonicity preferences were also correlated with the number of years subjects had spent playing a musical instrument, suggesting that exposure to music amplifies preferences for harmonic frequencies because of their musical importance. Harmonic spectra are prominent features of natural sounds, and our results indicate that they also underlie the perception of consonance. 2010 Elsevier Ltd. All rights reserved.

Estimation of the break-even point for smoking cessation programs in pregnancy.

PubMed Central

Shipp, M; Croughan-Minihane, M S; Petitti, D B; Washington, A E

1992-01-01

BACKGROUND. Successful programs to help pregnant women quit smoking have been developed and evaluated, but formal smoking cessation programs are not a part of care at most prenatal sites. The cost of such programs may be an issue. Considering the costs of adverse maternal and infant outcomes resulting from smoking, we estimated there would be an amount of money a prenatal program could invest in smoking cessation and still "break even" economically. METHODS. A model was developed and published data, along with 1989 hospital charge data, were used to arrive at a break-even point for smoking cessation programs in pregnancy. RESULTS. Using overall United States data, we arrived at a break-even cost of $32 per pregnant woman. When these data were varied to fit specific US populations, the break-even costs varied from $10 to $237, with the incidence of preterm low birth weight having the most impact on the cost. CONCLUSIONS. It may be advisable to invest greater amounts of money in a prenatal smoking cessation program for some populations. However, for every population there is an amount that can be invested while still breaking even. PMID:1536354

In trans paired nicking triggers seamless genome editing without double-stranded DNA cutting.

PubMed

Chen, Xiaoyu; Janssen, Josephine M; Liu, Jin; Maggio, Ignazio; 't Jong, Anke E J; Mikkers, Harald M M; Gonçalves, Manuel A F V

2017-09-22

Precise genome editing involves homologous recombination between donor DNA and chromosomal sequences subjected to double-stranded DNA breaks made by programmable nucleases. Ideally, genome editing should be efficient, specific, and accurate. However, besides constituting potential translocation-initiating lesions, double-stranded DNA breaks (targeted or otherwise) are mostly repaired through unpredictable and mutagenic non-homologous recombination processes. Here, we report that the coordinated formation of paired single-stranded DNA breaks, or nicks, at donor plasmids and chromosomal target sites by RNA-guided nucleases based on CRISPR-Cas9 components, triggers seamless homology-directed gene targeting of large genetic payloads in human cells, including pluripotent stem cells. Importantly, in addition to significantly reducing the mutagenicity of the genome modification procedure, this in trans paired nicking strategy achieves multiplexed, single-step, gene targeting, and yields higher frequencies of accurately edited cells when compared to the standard double-stranded DNA break-dependent approach.CRISPR-Cas9-based gene editing involves double-strand breaks at target sequences, which are often repaired by mutagenic non-homologous end-joining. Here the authors use Cas9 nickases to generate coordinated single-strand breaks in donor and target DNA for precise homology-directed gene editing.

Preference for language in early infancy: the human language bias is not speech specific.

PubMed

Krentz, Ursula C; Corina, David P

2008-01-01

Fundamental to infants' acquisition of their native language is an inherent interest in the language spoken around them over non-linguistic environmental sounds. The following studies explored whether the bias for linguistic signals in hearing infants is specific to speech, or reflects a general bias for all human language, spoken and signed. Results indicate that 6-month-old infants prefer an unfamiliar, visual-gestural language (American Sign Language) over non-linguistic pantomime, but 10-month-olds do not. These data provide evidence against a speech-specific bias in early infancy and provide insights into those properties of human languages that may underlie this language-general attentional bias.

Determination of human DNA polymerase utilization for the repair of a model ionizing radiation-induced DNA strand break lesion in a defined vector substrate

NASA Technical Reports Server (NTRS)

Winters, T. A.; Russell, P. S.; Kohli, M.; Dar, M. E.; Neumann, R. D.; Jorgensen, T. J.

1999-01-01

Human DNA polymerase and DNA ligase utilization for the repair of a major class of ionizing radiation-induced DNA lesion [DNA single-strand breaks containing 3'-phosphoglycolate (3'-PG)] was examined using a novel, chemically defined vector substrate containing a single, site-specific 3'-PG single-strand break lesion. In addition, the major human AP endonuclease, HAP1 (also known as APE1, APEX, Ref-1), was tested to determine if it was involved in initiating repair of 3'-PG-containing single-strand break lesions. DNA polymerase beta was found to be the primary polymerase responsible for nucleotide incorporation at the lesion site following excision of the 3'-PG blocking group. However, DNA polymerase delta/straightepsilon was also capable of nucleotide incorporation at the lesion site following 3'-PG excision. In addition, repair reactions catalyzed by DNA polymerase beta were found to be most effective in the presence of DNA ligase III, while those catalyzed by DNA polymerase delta/straightepsilon appeared to be more effective in the presence of DNA ligase I. Also, it was demonstrated that the repair initiating 3'-PG excision reaction was not dependent upon HAP1 activity, as judged by inhibition of HAP1 with neutralizing HAP1-specific polyclonal antibody.

Aggression and Rule-breaking: Heritability and stability of antisocial behavior problems in childhood and adolescence

PubMed Central

Niv, Sharon; Tuvblad, Catherine; Raine, Adrian; Baker, Laura A.

2013-01-01

Purpose This twin study examined the structure of genetic and environmental influences on aggression and rule-breaking in order to examine change and stability across the span of childhood to mid-adolescence. Methods Behavioral assessments were conducted at two time points: age 9–10 years and 14–15 years. Using behavioral genetics biometric modeling, the longitudinal structure of influences was investigated. Results Aggression and rule-breaking were found to be influenced by a latent common factor of antisocial behavior (ASB) within each wave of data collection. The childhood-age common factor of ASB was influenced by 41% genetics, 40% shared environment and 19% nonshared environment. In adolescence, 41% of influences on the common factor were novel and entirely genetic, while the remainder of influences were stable across time. Additionally, both aggression and rule-breaking within each wave were found to have unique influences not common across subscales or across waves, highlighting specificity of influences on different problem behaviors at both ages. Conclusions This research sheds light on the commonality of influences on etiology of different forms of antisocial behavior, and suggests future directions for research into intervention for antisocial behavior problems in youth, such as investigation of adolescence-specific environmental influences on the development of antisocial behavior problems. PMID:24347737

Concerns about losing control when breaking bad news to terminally ill patients with cancer: physicians' perspective.

PubMed

Friedrichsen, Maria; Milberg, Anna

2006-06-01

To study and explore problems perceived by physicians when breaking bad news to advanced cancer patients about discontinuing or not offering tumor-specific treatment due to incurable cancer. A qualitative phenomenographic interview study. The county of Ostergötland in Sweden. Thirty physicians with different demographic characteristics. According to the physicians' answers breaking bad news was perceived as involving a risk of losing control in different ways, regarding emotions, oneself, confidence, professionalism and patient trust. Four different main categories described as problems were identified; perceptions focusing on existential thoughts, relationships, knowledge, and perceptions related to time and environmental disturbances. Physicians perceived that breaking bad news to dying patients with cancer involved a risk of losing control. Existential thoughts and a lack of knowledge contribute to this risk. Theoretical education in existentiality/spirituality and clinical practice in a palliative context may help maintaining control.

Double strand breaks may be a missing link between entropy and aging.

PubMed

Lenart, Peter; Bienertová-Vašků, Julie

2016-07-01

It has been previously suggested that an increase in entropy production leads to aging. However, the mechanisms linking increased entropy production in living mass to aging are currently unclear. Even though entropy cannot be easily associated with any specific molecular damage, the increase of entropy in structural mass may be connected with heat stress, which is known to generate double strand breaks. Double strand breaks, which are in turn known to play an important role in process of aging, are thus connected to both aging and an increase of entropy. In view of these associations, we propose a new model where the increase of entropy leads to the formation of double strand breaks, resulting in an aging phenotype. This not only offers a new perspective on aging research and facilitates experimental validation, but could also serve as a useful explanatory tool. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effective anti-Alzheimer Aβ therapy involves depletion of specific Aβ oligomer subtypes

PubMed Central

Knight, Elysse M.; Kim, Soong Ho; Kottwitz, Jessica C.; Hatami, Asa; Albay, Ricardo; Suzuki, Akinobu; Lublin, Alex; Alberini, Cristina M.; Klein, William L.; Szabo, Paul; Relkin, Norman R.; Ehrlich, Michelle; Glabe, Charles G.; Steele, John W.

2016-01-01

Background: Recent studies have implicated specific assembly subtypes of β-amyloid (Aβ) peptide, specifically soluble oligomers (soAβ) as disease-relevant structures that may underlie memory loss in Alzheimer disease. Removing existing soluble and insoluble Aβ assemblies is thought to be essential for any attempt at stabilizing brain function and slowing cognitive decline in Alzheimer disease. IV immunoglobulin (IVIg) therapies have been shown to contain naturally occurring polyclonal antibodies that recognize conformational neoepitopes of soluble or insoluble Aβ assemblies including soAβ. These naturally occurring polyclonal antibodies have been suggested to underlie the apparent clinical benefits of IVIg. However, direct evidence linking anti-Aβ antibodies to the clinical bioactivity of IVIg has been lacking. Methods: Five-month-old female Dutch APP E693Q mice were treated for 3 months with neat IVIg or with IVIg that had been affinity-depleted over immobilized Aβ conformers in 1 of 2 assembly states. Memory was assessed in a battery of tests followed by quantification of brain soAβ levels using standard anti-soAβ antibodies. Results: We provide evidence that NU4-type soAβ (NU4-soAβ) assemblies accumulate in the brains of Dutch APP E693Q mice and are associated with defects in memory, even in the absence of insoluble Aβ plaques. Memory benefits were associated with depletion from APP E693Q mouse brain of NU4-soAβ and A11-soAβ but not OC-type fibrillar Aβ oligomers. Conclusions: We propose that targeting of specific soAβ assembly subtypes may be an important consideration in the therapeutic and/or prophylactic benefit of anti-Aβ antibody drugs. PMID:27218118

DNA Resection at Chromosome Breaks Promotes Genome Stability by Constraining Non-Allelic Homologous Recombination

PubMed Central

Koshland, Douglas

2012-01-01

DNA double-strand breaks impact genome stability by triggering many of the large-scale genome rearrangements associated with evolution and cancer. One of the first steps in repairing this damage is 5′→3′ resection beginning at the break site. Recently, tools have become available to study the consequences of not extensively resecting double-strand breaks. Here we examine the role of Sgs1- and Exo1-dependent resection on genome stability using a non-selective assay that we previously developed using diploid yeast. We find that Saccharomyces cerevisiae lacking Sgs1 and Exo1 retains a very efficient repair process that is highly mutagenic to genome structure. Specifically, 51% of cells lacking Sgs1 and Exo1 repair a double-strand break using repetitive sequences 12–48 kb distal from the initial break site, thereby generating a genome rearrangement. These Sgs1- and Exo1-independent rearrangements depend partially upon a Rad51-mediated homologous recombination pathway. Furthermore, without resection a robust cell cycle arrest is not activated, allowing a cell with a single double-strand break to divide before repair, potentially yielding multiple progeny each with a different rearrangement. This profusion of rearranged genomes suggests that cells tolerate any dangers associated with extensive resection to inhibit mutagenic pathways such as break-distal recombination. The activation of break-distal recipient repeats and amplification of broken chromosomes when resection is limited raise the possibility that genome regions that are difficult to resect may be hotspots for rearrangements. These results may also explain why mutations in resection machinery are associated with cancer. PMID:22479212

Resonant Formation of Strand Breaks in Sensitized Oligonucleotides Induced by Low-Energy Electrons (0.5-9 eV).

PubMed

Schürmann, Robin; Tsering, Thupten; Tanzer, Katrin; Denifl, Stephan; Kumar, S V K; Bald, Ilko

2017-08-28

Halogenated nucleobases are used as radiosensitizers in cancer radiation therapy, enhancing the reactivity of DNA to secondary low-energy electrons (LEEs). LEEs induce DNA strand breaks at specific energies (resonances) by dissociative electron attachment (DEA). Although halogenated nucleobases show intense DEA resonances at various electron energies in the gas phase, it is inherently difficult to investigate the influence of halogenated nucleobases on the actual DNA strand breakage over the broad range of electron energies at which DEA can take place (<12 eV). By using DNA origami nanostructures, we determined the energy dependence of the strand break cross-section for oligonucleotides modified with 8-bromoadenine ( 8Br A). These results were evaluated against DEA measurements with isolated 8Br A in the gas phase. Contrary to expectations, the major contribution to strand breaks is from resonances at around 7 eV while resonances at very low energy (<2 eV) have little influence on strand breaks. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

RG-invariant sum rule in a generalization of anomaly-mediated SUSY-breaking models

NASA Astrophysics Data System (ADS)

Carena, Marcela; Huitu, Katri; Kobayashi, Tatsuo

2001-01-01

We study a generalization of anomaly-mediated supersymmetry-breaking (AMSB) scenarios, under the assumption that the effects of the high-scale theory do not completely decouple and that D-term type contributions can therefore be present. We investigate the effect of such possible D-term additional contributions to soft scalar masses by requiring that, for non-vanishing, renormalizable Yukawa couplings Yijk, the sum of squared soft supersymmetry breaking mass parameters, M2ijk≡mi2+mj2+mk2, is RG-invariant, in the sense that it becomes independent of the specific ultraviolet boundary conditions as it occurs in the AMSB models. This type of models can avoid the problem of tachyonic solutions for the slepton mass spectrum present in AMSB scenarios. We implement the electroweak symmetry breaking condition and explore the sparticle spectrum associated with this framework. To show the possible diversity of the sparticle spectrum, we consider two examples, one in which the D-terms induce a common soft supersymmetry breaking mass term for all sfermion masses, and another one in which a light stop can be present in the spectrum.

Mission analysis and performance specification studies report, appendix A

NASA Technical Reports Server (NTRS)

1979-01-01

The Near Term Hybrid Passenger Vehicle Development Program tasks included defining missions, developing distributions of daily travel and composite driving cycles for these missions, providing information necessary to estimate the potential replacement of the existing fleet by hybrids, and estimating acceleration/gradeability performance requirements for safe operation. The data was then utilized to develop mission specifications, define reference vehicles, develop hybrid vehicle performance specifications, and make fuel consumption estimates for the vehicles. The major assumptions which underlie the approach taken to the mission analysis and development of performance specifications are the following: the daily operating range of a hybrid vehicle should not be limited by the stored energy capacity and the performance of such a vehicle should not be strongly dependent on the battery state of charge.

Validity of two wearable monitors to estimate breaks from sedentary time

PubMed Central

Lyden, Kate; Kozey-Keadle, Sarah L.; Staudenmayer, John W.; Freedson, Patty S.

2012-01-01

Investigations employing wearable monitors have begun to examine how sedentary time behaviors influence health. Purpose To demonstrate the utility of a measure of sedentary behavior and to validate the activPAL and ActiGraph GT3X for estimating measures of sedentary behavior: absolute number of breaks and break-rate. Methods Thirteen participants completed two, 10-hour conditions. During the baseline condition, participants performed normal daily activity and during the treatment condition, participants were asked to reduce and break-up their sedentary time. In each condition, participants wore two ActiGraph GT3X monitors and one activPAL. The ActiGraph was tested using the low frequency extension filter (AG-LFE) and the normal filter (AG-Norm). For both ActiGraph monitors two count cut-points to estimate sedentary time were examined: 100 and 150 counts∙min−1. Direct observation served as the criterion measure of total sedentary time, absolute number of breaks from sedentary time and break-rate (number of breaks per sedentary hour [brks.sed-hr−1]). Results Break-rate was the only metric sensitive to changes in behavior between baseline (5.1 [3.3 to 6.8] brks.sed-hr−1) and treatment conditions (7.3 [4.7 to 9.8] brks.sed-hr−1) (mean [95% CI]). The activPAL produced valid estimates of all sedentary behavior measures and was sensitive to changes in break-rate between conditions (baseline: 5.1 [2.8 to 7.1] brks.sed-hr−1, treatment: 8.0 [5.8 to 10.2] brks.sed-hr−1). In general, the AG-LFE and AG-Norm were not accurate in estimating break-rate or absolute number of breaks and were not sensitive to changes between conditions. Conclusion This study demonstrates the utility of expressing breaks from sedentary time as a rate per sedentary hour, a metric specifically relevant to free-living behavior, and provides further evidence that the activPAL is a valid tool to measure components of sedentary behavior in free-living environments. PMID:22648343

Breaking bad news of cancer diagnosis - Perception of the cancer patients in a rural community in Malaysia.

PubMed

Bain, Mathew Gabriel; Lian, Cheah Whye; Thon, Chang Ching

2014-04-01

Breaking of bad news is an important component in the management of cancer patients. This study aimed to assess the perceptions of breaking bad news of cancer diagnosis. It was a cross-sectional study using Breaking Bad News Assessment Schedule (BAS) questionnaire on cancer patients in Serian district. Using snowballing sampling method, a total of 134 patients were interviewed face-to-face after the consent was obtained from each of the respondents. Data was entered and analyzed using SPSS version 19.0. Majority were comfortable with the current method of breaking bad news. The main aspects found to be the areas of concern were the importance of the usage of body language, management of time and identifying patients' key area of concerns. There were significant difference between sex and "information giving" (P = 0.028) and "general consideration" (P = 0.016) and also between "the age and setting the scene" (P = 0.042). Significant difference was also found between the types of cancer and "the setting of scene" (P = 0.018), "breaking bad news technique" (P = 0.010), "eliciting concerns" (P = 0.003) and "information giving" (P = 0.004). Good and effective communication skill of breaking bad news is vital in the management of cancer patients. As the incidence of new cases of cancer increase every year, breaking of bad news has become a pertinent to the medical professionals' role. Specific aspects of communication skills based on local characteristics should be more emphasized in the formulation of training for doctors.

Kuru

MedlinePlus

... The NINDS funds research to better understand the genetic, molecular, and cellular mechanisms that underlie the TSE diseases. ... The NINDS funds research to better understand the genetic, molecular, and cellular mechanisms that underlie the TSE diseases. ...

75 FR 45677 - Draft Regulatory Guide, DG-1216,”Plant-Specific Applicability of Transition Break Size Specified...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0229] Draft Regulatory Guide, DG-1216,''Plant-Specific... Commission (NRC) is extending the public comment period for DG-1216 from August 25, 2010 to November 8, 2010... [email protected] . The Draft Regulatory Guide, DG-1216, ``Plant- Specific Applicability of...

Progressive gender differences of structural brain networks in healthy adults: a longitudinal, diffusion tensor imaging study.

PubMed

Sun, Yu; Lee, Renick; Chen, Yu; Collinson, Simon; Thakor, Nitish; Bezerianos, Anastasios; Sim, Kang

2015-01-01

Sexual dimorphism in the brain maturation during childhood and adolescence has been repeatedly documented, which may underlie the differences in behaviors and cognitive performance. However, our understanding of how gender modulates the development of structural connectome in healthy adults is still not entirely clear. Here we utilized graph theoretical analysis of longitudinal diffusion tensor imaging data over a five-year period to investigate the progressive gender differences of brain network topology. The brain networks of both genders showed prominent economical "small-world" architecture (high local clustering and short paths between nodes). Additional analysis revealed a more economical "small-world" architecture in females as well as a greater global efficiency in males regardless of scan time point. At the regional level, both increased and decreased efficiency were found across the cerebral cortex for both males and females, indicating a compensation mechanism of cortical network reorganization over time. Furthermore, we found that weighted clustering coefficient exhibited significant gender-time interactions, implying different development trends between males and females. Moreover, several specific brain regions (e.g., insula, superior temporal gyrus, cuneus, putamen, and parahippocampal gyrus) exhibited different development trajectories between males and females. Our findings further prove the presence of sexual dimorphism in brain structures that may underlie gender differences in behavioral and cognitive functioning. The sex-specific progress trajectories in brain connectome revealed in this work provide an important foundation to delineate the gender related pathophysiological mechanisms in various neuropsychiatric disorders, which may potentially guide the development of sex-specific treatments for these devastating brain disorders.

Testing the role of reward and punishment sensitivity in avoidance behavior: a computational modeling approach

PubMed Central

Sheynin, Jony; Moustafa, Ahmed A.; Beck, Kevin D.; Servatius, Richard J.; Myers, Catherine E.

2015-01-01

Exaggerated avoidance behavior is a predominant symptom in all anxiety disorders and its degree often parallels the development and persistence of these conditions. Both human and non-human animal studies suggest that individual differences as well as various contextual cues may impact avoidance behavior. Specifically, we have recently shown that female sex and inhibited temperament, two anxiety vulnerability factors, are associated with greater duration and rate of the avoidance behavior, as demonstrated on a computer-based task closely related to common rodent avoidance paradigms. We have also demonstrated that avoidance is attenuated by the administration of explicit visual signals during “non-threat” periods (i.e., safety signals). Here, we use a reinforcement-learning network model to investigate the underlying mechanisms of these empirical findings, with a special focus on distinct reward and punishment sensitivities. Model simulations suggest that sex and inhibited temperament are associated with specific aspects of these sensitivities. Specifically, differences in relative sensitivity to reward and punishment might underlie the longer avoidance duration demonstrated by females, whereas higher sensitivity to punishment might underlie the higher avoidance rate demonstrated by inhibited individuals. Simulations also suggest that safety signals attenuate avoidance behavior by strengthening the competing approach response. Lastly, several predictions generated by the model suggest that extinction-based cognitive-behavioral therapies might benefit from the use of safety signals, especially if given to individuals with high reward sensitivity and during longer safe periods. Overall, this study is the first to suggest cognitive mechanisms underlying the greater avoidance behavior observed in healthy individuals with different anxiety vulnerabilities. PMID:25639540

Mathematical model of depolarization mechanism of conducted vasoreactivity

NASA Astrophysics Data System (ADS)

Neganova, Anastasiia Y.; Stiukhina, Elena S.; Postnov, Dmitry E.

2015-03-01

We address the problem of conducted vasodilation, the phenomenon which is also known as functional hyperemia. Specifically, we test the mechanism of nondecremental propagation of electric signals along endothelial cell layer recently hypothesized by Figueroa et al. By means of functional modeling we focus on possible nonlinear mechanisms that can underlie such regenerative pulse transmission (RPT). Since endothelial cells (EC) are generally known as electrically inexcitable, the possible role of ECs in RPT mechanisms is not evident. By means of mathematical modeling we check the dynamical self-consistency of Figueroa's hypothesis, as well as estimate the possible contribution of specific ionic currents to the suggested RPT mechanism.

Autonomic neuropathies

NASA Technical Reports Server (NTRS)

Low, P. A.

1998-01-01

A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.

Intelligence, competitive altruism, and "clever silliness" may underlie bias in academe.

PubMed

Madison, Guy; Dutton, Edward; Stern, Charlotta

2017-01-01

Why is social bias and its depressing effects on low-status or low-performing groups exaggerated? We show that the higher intelligence of academics has at best a very weak effect on reducing their bias, facilitates superficially justifying their biases, and may make them better at understanding the benefits of social conformity in general and competitive altruism specifically. We foresee a surge in research examining these mechanisms and recommend, meanwhile, reviving and better observing scientific ideals.

Caffeine, Adenosine Receptors and Estrogen in Toxin Models of Parkinson’s Disease

DTIC Science & Technology

2010-10-30

processed for A2A receptor immunohistochemsitry (B) with a HRP-coupled secondary antibody yielding a (brown) DAB reaction product more but specifically...the striatum of ‘floxed’ A2A gene mice treated 6-8 weeks later with saline or MPTP. The processing and analyses of their brain tissues is currently...coffee (but not decaffeinated coffee). The mechanisms that underlie this epidemiological correla- tion remain unclear. One hypothesis that caffeine

View-Based Models of 3D Object Recognition and Class-Specific Invariance

DTIC Science & Technology

1994-04-01

underlie recognition of geon-like com- ponents (see Edelman, 1991 and Biederman , 1987 ). I(X -_ ta)II1y = (X - ta)TWTW(x -_ ta) (3) View-invariant features...Institute of Technology, 1993. neocortex. Biological Cybernetics, 1992. 14] I. Biederman . Recognition by components: a theory [20] B. Olshausen, C...Anderson, and D. Van Essen. A of human image understanding. Psychol. Review, neural model of visual attention and invariant pat- 94:115-147, 1987 . tern

Prenatal Exposure to Arsenic and Cadmium Impacts Infectious Disease-Related Genes within the Glucocorticoid Receptor Signal Transduction Pathway

PubMed Central

Rager, Julia E.; Yosim, Andrew; Fry, Rebecca C.

2014-01-01

There is increasing evidence that environmental agents mediate susceptibility to infectious disease. Studies support the impact of prenatal/early life exposure to the environmental metals inorganic arsenic (iAs) and cadmium (Cd) on increased risk for susceptibility to infection. The specific biological mechanisms that underlie such exposure-mediated effects remain understudied. This research aimed to identify key genes/signal transduction pathways that associate prenatal exposure to these toxic metals with changes in infectious disease susceptibility using a Comparative Genomic Enrichment Method (CGEM). Using CGEM an infectious disease gene (IDG) database was developed comprising 1085 genes with known roles in viral, bacterial, and parasitic disease pathways. Subsequently, datasets collected from human pregnancy cohorts exposed to iAs or Cd were examined in relationship to the IDGs, specifically focusing on data representing epigenetic modifications (5-methyl cytosine), genomic perturbations (mRNA expression), and proteomic shifts (protein expression). A set of 82 infection and exposure-related genes was identified and found to be enriched for their role in the glucocorticoid receptor signal transduction pathway. Given their common identification across numerous human cohorts and their known toxicological role in disease, the identified genes within the glucocorticoid signal transduction pathway may underlie altered infectious disease susceptibility associated with prenatal exposures to the toxic metals iAs and Cd in humans. PMID:25479081

Similar exemplar pooling processes underlie the learning of facial identity and handwriting style: Evidence from typical observers and individuals with Autism.

PubMed

Ipser, Alberta; Ring, Melanie; Murphy, Jennifer; Gaigg, Sebastian B; Cook, Richard

2016-05-01

Considerable research has addressed whether the cognitive and neural representations recruited by faces are similar to those engaged by other types of visual stimuli. For example, research has examined the extent to which objects of expertise recruit holistic representation and engage the fusiform face area. Little is known, however, about the domain-specificity of the exemplar pooling processes thought to underlie the acquisition of familiarity with particular facial identities. In the present study we sought to compare observers' ability to learn facial identities and handwriting styles from exposure to multiple exemplars. Crucially, while handwritten words and faces differ considerably in their topographic form, both learning tasks share a common exemplar pooling component. In our first experiment, we find that typical observers' ability to learn facial identities and handwriting styles from exposure to multiple exemplars correlates closely. In our second experiment, we show that observers with Autism Spectrum Disorder (ASD) are impaired at both learning tasks. Our findings suggest that similar exemplar pooling processes are recruited when learning facial identities and handwriting styles. Models of exemplar pooling originally developed to explain face learning, may therefore offer valuable insights into exemplar pooling across a range of domains, extending beyond faces. Aberrant exemplar pooling, possibly resulting from structural differences in the inferior longitudinal fasciculus, may underlie difficulties recognising familiar faces often experienced by individuals with ASD, and leave observers overly reliant on local details present in particular exemplars. Copyright © 2016 Elsevier Ltd. All rights reserved.

Symmetry breaking: a tool to unveil the topology of chaotic scattering with three degrees of freedom

NASA Astrophysics Data System (ADS)

Jung, Christof; Zapfe, W. P. Karel; Merlo, Olivier; Seligman, T. H.

2010-12-01

We shall use symmetry breaking as a tool to attack the problem of identifying the topology of chaotic scatteruing with more then two degrees of freedom. specifically we discuss the structure of the homoclinic/heteroclinic tangle and the connection between the chaotic invariant set, the scattering functions and the singularities in the cross section for a class of scattering systems with one open and two closed degrees of freedom.

Symmetry breaking: a tool to unveil the topology of chaotic scattering with three degrees of freedom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jung, Christof; Zapfe, W. P. Karel; Seligman, T. H.

2010-12-23

We shall use symmetry breaking as a tool to attack the problem of identifying the topology of chaotic scatteruing with more then two degrees of freedom. specifically we discuss the structure of the homoclinic/heteroclinic tangle and the connection between the chaotic invariant set, the scattering functions and the singularities in the cross section for a class of scattering systems with one open and two closed degrees of freedom.

Sequence dependence of electron-induced DNA strand breakage revealed by DNA nanoarrays

PubMed Central

Keller, Adrian; Rackwitz, Jenny; Cauët, Emilie; Liévin, Jacques; Körzdörfer, Thomas; Rotaru, Alexandru; Gothelf, Kurt V.; Besenbacher, Flemming; Bald, Ilko

2014-01-01

The electronic structure of DNA is determined by its nucleotide sequence, which is for instance exploited in molecular electronics. Here we demonstrate that also the DNA strand breakage induced by low-energy electrons (18 eV) depends on the nucleotide sequence. To determine the absolute cross sections for electron induced single strand breaks in specific 13 mer oligonucleotides we used atomic force microscopy analysis of DNA origami based DNA nanoarrays. We investigated the DNA sequences 5′-TT(XYX)3TT with X = A, G, C and Y = T, BrU 5-bromouracil and found absolute strand break cross sections between 2.66 · 10−14 cm2 and 7.06 · 10−14 cm2. The highest cross section was found for 5′-TT(ATA)3TT and 5′-TT(ABrUA)3TT, respectively. BrU is a radiosensitizer, which was discussed to be used in cancer radiation therapy. The replacement of T by BrU into the investigated DNA sequences leads to a slight increase of the absolute strand break cross sections resulting in sequence-dependent enhancement factors between 1.14 and 1.66. Nevertheless, the variation of strand break cross sections due to the specific nucleotide sequence is considerably higher. Thus, the present results suggest the development of targeted radiosensitizers for cancer radiation therapy. PMID:25487346

Myeloid- and lymphoid-specific breakpoint cluster regions in chromosome band 13q14 in acute leukemia.

PubMed

Coignet, L J; Lima, C S; Min, T; Streubel, B; Swansbury, J; Telford, N; Swanton, S; Bowen, A; Nagai, M; Catovsky, D; Fonatsch, C; Dyer, M J

1999-07-01

Abnormalities of chromosome band 13q14 occur in hematologic malignancies of all lineages and at all stages of differentiation. Unlike other chromosomal translocations, which are usually specific for a given lineage, the chromosomal translocation t(12;13)(p12;q14) has been observed in both B-cell and T-cell precursor acute lymphoblastic leukemia (BCP-, TCP-ALL), in differentiated and undifferentiated acute myeloblastic leukemia (AML), and in chronic myeloid leukemia (CML) at progression to blast crisis. The nature of these translocations and their pathologic consequences remain unknown. To begin to define the gene(s) involved on chromosome 13, we have performed fluorescence in situ hybridization (FISH) using a panel of YACs from the region, on a series of 10 cases of acute leukemia with t(12;13)(p12;q14) and 1 case each with "variant" translocations including t(12;13)(q21;q14), t(10;13)(q24;q14) and t(9;13)(p21;q14). In 8/13 cases/cell lines, the 13q14 break fell within a single 1.4 Mb CEPH MegaYAC. This YAC fell immediately telomeric of the forkhead (FKHR) gene, which is disrupted in the t(2;13)(q35;q14) seen in pediatric alveolar rhabdomyosarcoma. Seven of the 8 cases with breaks in this YAC were AML. In 4/13 cases, the 13q14 break fell within a 1.7-Mb YAC located about 3 Mb telomeric of the retinoblastoma (RB1) gene: all 4 cases were ALL. One case of myelodysplastic syndrome exhibited a break within 13q12, adjacent to the BRCA2 gene. These data indicate the presence of myeloid- and lymphoid-specific breakpoint cluster regions within chromosome band 13q14 in acute leukemia.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roos, E.; Maier, V.; Nagel, G.

The break preclusion concept is based on {open_quotes}KTA rules{close_quotes}, {open_quotes}RSK guidelines{close_quotes} and {open_quotes}Rahmenspeziflkation Basissicherheit{close_quotes}. These fundamental rules containing for example requirements on material, design, calculation, manufacturing and testing procedures are explained and the technical realisation is shown by means of examples. The proof of the quality of these piping systems can be executed by means of fracture mechanics calculations by showing that in every case the leakage monitoring system already detect cracks which are clearly smaller than the critical crack. Thus the leak before break behavior and the break preclusion concept is implicitly affirmed. In order to further diminish conservativitiesmore » in the fracture mechanics procedures, specific research projects are executed which are explained in this contribution.« less

Effective field theory of emergent symmetry breaking in deformed atomic nuclei

DOE PAGES

Papenbrock, Thomas F.; Weidenmüller, H. A.

2015-09-03

Spontaneous symmetry breaking in non-relativistic quantum systems has previously been addressed in the framework of effective field theory. Low-lying excitations are constructed from Nambu–Goldstone modes using symmetry arguments only. In this study, we extend that approach to finite systems. The approach is very general. To be specific, however, we consider atomic nuclei with intrinsically deformed ground states. The emergent symmetry breaking in such systems requires the introduction of additional degrees of freedom on top of the Nambu–Goldstone modes. Symmetry arguments suffice to construct the low-lying states of the system. Lastly, in deformed nuclei these are vibrational modes each of whichmore » serves as band head of a rotational band.« less

The concept of quasi-tissue-equivalent nanodosimeter based on the glow peak 5a/5 in LiF:Mg,Ti (TLD-100).

PubMed

Oster, L; Horowitz, Y S; Biderman, S; Haddad, J

2003-12-01

We demonstrate the viability of the concept of using existing molecular nanostructures in thermoluminescent solid-state materials as solid-state nanodosimeters. The concept is based on mimicking radiobiology (specifically the ionization density dependence of double strand breaks in DNA) by using the similar ionization density dependence of simultaneous electron-hole capture in spatially correlated trapping and luminescent centres pairs in the thermoluminescence of LiF:Mg,Ti. This simultaneous electron-hole capture has been shown to lead to ionization density dependence in the relative intensity of peak 5a to peak 5 similar to the ratio of double-strand breaks to single-strand breaks for low energy He ions.

The role of Pif1p, a DNA helicase in Saccharomyces cerevisiae, in maintaining mitochondrial DNA.

PubMed

Cheng, Xin; Dunaway, Stephen; Ivessa, Andreas S

2007-05-01

Mitochondrial DNA (mtDNA) is highly susceptible to oxidative and chemically induced damage, and these insults lead to a number of diseases. In Saccharomyces cerevisiae, the DNA helicase Pif1p is localized to the nucleus and mitochondria. We show that pif1 mutant cells are sensitive to ethidium bromide-induced damage and this mtDNA is prone to fragmentation. We also show that Pif1p associates with mtDNA. In pif1 mutant cells, mtDNA breaks at specific sites that exhibit Pif1-dependent recombination. We conclude that Pif1p participates in the protection from double-stranded (ds) DNA breaks or alternatively in the repair process of dsDNA breaks in mtDNA.

Urbanization and human health in urban India: institutional analysis of water-borne diseases in Ahmedabad.

PubMed

Saravanan, V S; Ayessa Idenal, Marissa; Saiyed, Shahin; Saxena, Deepak; Gerke, Solvay

2016-10-01

Diseases are rapidly urbanizing. Ageing infrastructures, high levels of inequality, poor urban governance, rapidly growing economies and highly dense and mobile populations all create environments rife for water-borne diseases. This article analyzes the role of institutions as crosscutting entities among a myriad of factors that breed water-borne diseases in the city of Ahmedabad, India. It applies 'path dependency' and a 'rational choice' perspective to understand the factors facilitating the breeding of diseases. This study is based on household surveys of approximately 327 households in two case study wards and intermittent interviews with key informants over a period of 2 years. Principle component analysis is applied to reduce the data and convert a set of observations, which potentially correlate with each other, into components. Institutional analyses behind these components reveal the role of social actors in exploiting the deeply rooted inefficiencies affecting urban health. This has led to a vicious cycle; breaking this cycle requires understanding the political dynamics that underlie the exposure and prevalence of diseases to improve urban health. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Social Adversity and Antisocial Behavior: Mediating Effects of Autonomic Nervous System Activity.

PubMed

Fagan, Shawn E; Zhang, Wei; Gao, Yu

2017-11-01

The display of antisocial behaviors in children and adolescents has been of interest to criminologists and developmental psychologists for years. Exposure to social adversity is a well-documented predictor of antisocial behavior. Additionally, measures of autonomic nervous system (ANS) activity, including heart rate variability (HRV), pre-ejection period (PEP), and heart rate, have been associated with antisocial behaviors including rule-breaking and aggression. Social neuroscience research has begun to investigate how neurobiological underpinnings affect the relationship between social adversity and antisocial/psychopathic behavior in children and adolescents. This study investigated the potential mediating effects of ANS activity on the relationship between social adversity and antisocial behavior in a group of 7- to 10-year-old children from the community (N = 339; 48.2% male). Moderated multiple mediation analyses revealed that low resting heart rate, but not PEP or HRV, mediated the relationship between social adversity and antisocial behavior in males only. Social adversity but not ANS measures were associated with antisocial behavior in females. Findings have implications for understanding the neural influences that underlie antisocial behavior, illustrate the importance of the social environment regarding the expression of these behaviors, and highlight essential gender differences.

Intragenic origins due to short G1 phases underlie oncogene-induced DNA replication stress.

PubMed

Macheret, Morgane; Halazonetis, Thanos D

2018-03-01

Oncogene-induced DNA replication stress contributes critically to the genomic instability that is present in cancer. However, elucidating how oncogenes deregulate DNA replication has been impeded by difficulty in mapping replication initiation sites on the human genome. Here, using a sensitive assay to monitor nascent DNA synthesis in early S phase, we identified thousands of replication initiation sites in cells before and after induction of the oncogenes CCNE1 and MYC. Remarkably, both oncogenes induced firing of a novel set of DNA replication origins that mapped within highly transcribed genes. These ectopic origins were normally suppressed by transcription during G1, but precocious entry into S phase, before all genic regions had been transcribed, allowed firing of origins within genes in cells with activated oncogenes. Forks from oncogene-induced origins were prone to collapse, as a result of conflicts between replication and transcription, and were associated with DNA double-stranded break formation and chromosomal rearrangement breakpoints both in our experimental system and in a large cohort of human cancers. Thus, firing of intragenic origins caused by premature S phase entry represents a mechanism of oncogene-induced DNA replication stress that is relevant for genomic instability in human cancer.

A quantitative approach to painting styles

NASA Astrophysics Data System (ADS)

Vieira, Vilson; Fabbri, Renato; Sbrissa, David; da Fontoura Costa, Luciano; Travieso, Gonzalo

2015-01-01

This research extends a method previously applied to music and philosophy (Vilson Vieira et al., 2012), representing the evolution of art as a time-series where relations like dialectics are measured quantitatively. For that, a corpus of paintings of 12 well-known artists from baroque and modern art is analyzed. A set of 99 features is extracted and the features which most contributed to the classification of painters are selected. The projection space obtained provides the basis to the analysis of measurements. These quantitative measures underlie revealing observations about the evolution of painting styles, specially when compared with other humanity fields already analyzed: while music evolved along a master-apprentice tradition (high dialectics) and philosophy by opposition, painting presents another pattern: constant increasing skewness, low opposition between members of the same movement and opposition peaks in the transition between movements. Differences between baroque and modern movements are also observed in the projected "painting space": while baroque paintings are presented as an overlapped cluster, the modern paintings present minor overlapping and are disposed more widely in the projection than the baroque counterparts. This finding suggests that baroque painters shared aesthetics while modern painters tend to "break rules" and develop their own style.

Identification of conserved pathways of DNA-damage response and radiation protection by genome-wide RNAi.

PubMed

van Haaften, Gijs; Romeijn, Ron; Pothof, Joris; Koole, Wouter; Mullenders, Leon H F; Pastink, Albert; Plasterk, Ronald H A; Tijsterman, Marcel

2006-07-11

Ionizing radiation is extremely harmful for human cells, and DNA double-strand breaks (DSBs) are considered to be the main cytotoxic lesions induced. Improper processing of DSBs contributes to tumorigenesis, and mutations in DSB response genes underlie several inherited disorders characterized by cancer predisposition. Here, we performed a comprehensive screen for genes that protect animal cells against ionizing radiation. A total of 45 C. elegans genes were identified in a genome-wide RNA interference screen for increased sensitivity to ionizing radiation in germ cells. These genes include orthologs of well-known human cancer predisposition genes as well as novel genes, including human disease genes not previously linked to defective DNA-damage responses. Knockdown of eleven genes also impaired radiation-induced cell-cycle arrest, and seven genes were essential for apoptosis upon exposure to irradiation. The gene set was further clustered on the basis of increased sensitivity to DNA-damaging cancer drugs cisplatin and camptothecin. Almost all genes are conserved across animal phylogeny, and their relevance for humans was directly demonstrated by showing that their knockdown in human cells results in radiation sensitivity, indicating that this set of genes is important for future cancer profiling and drug development.

Cataloging the biomedical world of pain through semi-automated curation of molecular interactions

PubMed Central

Jamieson, Daniel G.; Roberts, Phoebe M.; Robertson, David L.; Sidders, Ben; Nenadic, Goran

2013-01-01

The vast collection of biomedical literature and its continued expansion has presented a number of challenges to researchers who require structured findings to stay abreast of and analyze molecular mechanisms relevant to their domain of interest. By structuring literature content into topic-specific machine-readable databases, the aggregate data from multiple articles can be used to infer trends that can be compared and contrasted with similar findings from topic-independent resources. Our study presents a generalized procedure for semi-automatically creating a custom topic-specific molecular interaction database through the use of text mining to assist manual curation. We apply the procedure to capture molecular events that underlie ‘pain’, a complex phenomenon with a large societal burden and unmet medical need. We describe how existing text mining solutions are used to build a pain-specific corpus, extract molecular events from it, add context to the extracted events and assess their relevance. The pain-specific corpus contains 765 692 documents from Medline and PubMed Central, from which we extracted 356 499 unique normalized molecular events, with 261 438 single protein events and 93 271 molecular interactions supplied by BioContext. Event chains are annotated with negation, speculation, anatomy, Gene Ontology terms, mutations, pain and disease relevance, which collectively provide detailed insight into how that event chain is associated with pain. The extracted relations are visualized in a wiki platform (wiki-pain.org) that enables efficient manual curation and exploration of the molecular mechanisms that underlie pain. Curation of 1500 grouped event chains ranked by pain relevance revealed 613 accurately extracted unique molecular interactions that in the future can be used to study the underlying mechanisms involved in pain. Our approach demonstrates that combining existing text mining tools with domain-specific terms and wiki-based visualization can facilitate rapid curation of molecular interactions to create a custom database. Database URL: ••• PMID:23707966

Cataloging the biomedical world of pain through semi-automated curation of molecular interactions.

PubMed

Jamieson, Daniel G; Roberts, Phoebe M; Robertson, David L; Sidders, Ben; Nenadic, Goran

2013-01-01

The vast collection of biomedical literature and its continued expansion has presented a number of challenges to researchers who require structured findings to stay abreast of and analyze molecular mechanisms relevant to their domain of interest. By structuring literature content into topic-specific machine-readable databases, the aggregate data from multiple articles can be used to infer trends that can be compared and contrasted with similar findings from topic-independent resources. Our study presents a generalized procedure for semi-automatically creating a custom topic-specific molecular interaction database through the use of text mining to assist manual curation. We apply the procedure to capture molecular events that underlie 'pain', a complex phenomenon with a large societal burden and unmet medical need. We describe how existing text mining solutions are used to build a pain-specific corpus, extract molecular events from it, add context to the extracted events and assess their relevance. The pain-specific corpus contains 765 692 documents from Medline and PubMed Central, from which we extracted 356 499 unique normalized molecular events, with 261 438 single protein events and 93 271 molecular interactions supplied by BioContext. Event chains are annotated with negation, speculation, anatomy, Gene Ontology terms, mutations, pain and disease relevance, which collectively provide detailed insight into how that event chain is associated with pain. The extracted relations are visualized in a wiki platform (wiki-pain.org) that enables efficient manual curation and exploration of the molecular mechanisms that underlie pain. Curation of 1500 grouped event chains ranked by pain relevance revealed 613 accurately extracted unique molecular interactions that in the future can be used to study the underlying mechanisms involved in pain. Our approach demonstrates that combining existing text mining tools with domain-specific terms and wiki-based visualization can facilitate rapid curation of molecular interactions to create a custom database. Database URL: •••

Decision Neuroscience: Neuroeconomics

PubMed Central

Smith, David V.; Huettel, Scott A.

2012-01-01

Few aspects of human cognition are more personal than the choices we make. Our decisions – from the mundane to the impossibly complex – continually shape the courses of our lives. In recent years, researchers have applied the tools of neuroscience to understand the mechanisms that underlie decision making, as part of the new discipline of decision neuroscience. A primary goal of this emerging field has been to identify the processes that underlie specific decision variables, including the value of rewards, the uncertainty associated with particular outcomes, and the consequences of social interactions. Recent work suggests potential neural substrates that integrate these variables, potentially reflecting a common neural currency for value, to facilitate value comparisons. Despite the successes of decision neuroscience research for elucidating brain mechanisms, significant challenges remain. These include building new conceptual frameworks for decision making, integrating research findings across disparate techniques and species, and extending results from neuroscience to shape economic theory. To overcome these challenges, future research will likely focus on interpersonal variability in decision making, with the eventual goal of creating biologically plausible models for individual choice. PMID:22754602

Between “design” and “bricolage”: Genetic networks, levels of selection, and adaptive evolution

PubMed Central

Wilkins, Adam S.

2007-01-01

The extent to which “developmental constraints” in complex organisms restrict evolutionary directions remains contentious. Yet, other forms of internal constraint, which have received less attention, may also exist. It will be argued here that a set of partial constraints below the level of phenotypes, those involving genes and molecules, influences and channels the set of possible evolutionary trajectories. At the top-most organizational level there are the genetic network modules, whose operations directly underlie complex morphological traits. The properties of these network modules, however, have themselves been set by the evolutionary history of the component genes and their interactions. Characterization of the components, structures, and operational dynamics of specific genetic networks should lead to a better understanding not only of the morphological traits they underlie but of the biases that influence the directions of evolutionary change. Furthermore, such knowledge may permit assessment of the relative degrees of probability of short evolutionary trajectories, those on the microevolutionary scale. In effect, a “network perspective” may help transform evolutionary biology into a scientific enterprise with greater predictive capability than it has hitherto possessed. PMID:17494754

Between "design" and "bricolage": genetic networks, levels of selection, and adaptive evolution.

PubMed

Wilkins, Adam S

2007-05-15

The extent to which "developmental constraints" in complex organisms restrict evolutionary directions remains contentious. Yet, other forms of internal constraint, which have received less attention, may also exist. It will be argued here that a set of partial constraints below the level of phenotypes, those involving genes and molecules, influences and channels the set of possible evolutionary trajectories. At the top-most organizational level there are the genetic network modules, whose operations directly underlie complex morphological traits. The properties of these network modules, however, have themselves been set by the evolutionary history of the component genes and their interactions. Characterization of the components, structures, and operational dynamics of specific genetic networks should lead to a better understanding not only of the morphological traits they underlie but of the biases that influence the directions of evolutionary change. Furthermore, such knowledge may permit assessment of the relative degrees of probability of short evolutionary trajectories, those on the microevolutionary scale. In effect, a "network perspective" may help transform evolutionary biology into a scientific enterprise with greater predictive capability than it has hitherto possessed.

Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells

PubMed Central

Hepworth, Matthew R.; Fung, Thomas C.; Masur, Samuel H.; Kelsen, Judith R.; McConnell, Fiona M.; Dubrot, Juan; Withers, David R.; Hugues, Stephanie; Farrar, Michael A.; Reith, Walter; Eberl, Gerard; Baldassano, Robert N.; Laufer, Terri M.; Elson, Charles O.; Sonnenberg, Gregory F.

2015-01-01

Inflammatory CD4+ T cell responses to self or commensal bacteria underlie the pathogenesis of autoimmunity and inflammatory bowel disease (IBD), respectively. While selection of self-specific T cells in the thymus limits responses to tissue antigens, the mechanisms that control selection of commensal bacteria-specific T cells remain poorly understood. Here we demonstrate that group 3 innate lymphoid cell (ILC3)-intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells, and that MHCII+ ILC3s directly induce cell death of activated commensal bacteria-specific T cells. Further, MHCII on human colonic ILC3s was reduced in pediatric IBD patients. Collectively, these results define a selection pathway for commensal bacteria-specific CD4+ T cells in the intestine, and suggest that this process is dysregulated in human IBD. PMID:25908663

Breaking bad news of cancer diagnosis – Perception of the cancer patients in a rural community in Malaysia

PubMed Central

Bain, Mathew Gabriel; Lian, Cheah Whye; Thon, Chang Ching

2014-01-01

Context: Breaking of bad news is an important component in the management of cancer patients. Aims: This study aimed to assess the perceptions of breaking bad news of cancer diagnosis. Settings and Design: It was a cross-sectional study using Breaking Bad News Assessment Schedule (BAS) questionnaire on cancer patients in Serian district. Materials and Methods: Using snowballing sampling method, a total of 134 patients were interviewed face-to-face after the consent was obtained from each of the respondents. Statistical Analysis Used: Data was entered and analyzed using SPSS version 19.0. Results: Majority were comfortable with the current method of breaking bad news. The main aspects found to be the areas of concern were the importance of the usage of body language, management of time and identifying patients’ key area of concerns. There were significant difference between sex and “information giving” (P = 0.028) and “general consideration” (P = 0.016) and also between “the age and setting the scene” (P = 0.042). Significant difference was also found between the types of cancer and “the setting of scene” (P = 0.018), “breaking bad news technique” (P = 0.010), “eliciting concerns” (P = 0.003) and “information giving” (P = 0.004). Conclusion: Good and effective communication skill of breaking bad news is vital in the management of cancer patients. As the incidence of new cases of cancer increase every year, breaking of bad news has become a pertinent to the medical professionals’ role. Specific aspects of communication skills based on local characteristics should be more emphasized in the formulation of training for doctors. PMID:24818107

Remote Sensing Characterization of Two-dimensional Wave Forcing in the Surf Zone

NASA Astrophysics Data System (ADS)

Carini, R. J.; Chickadel, C. C.; Jessup, A. T.

2016-02-01

In the surf zone, breaking waves drive longshore currents, transport sediment, shape bathymetry, and enhance air-sea gas and particle exchange. Furthermore, wave group forcing influences the generation and duration of rip currents. Wave breaking exhibits large gradients in space and time, making it challenging to measure in situ. Remote sensing technologies, specifically thermal infrared (IR) imagery, can provide detailed spatial and temporal measurements of wave breaking at the water surface. We construct two-dimensional maps of active wave breaking from IR imagery collected during the Surf Zone Optics Experiment in September 2010 at the US Army Corps of Engineers' Field Research Facility in Duck, NC. For each breaker identified in the camera's field of view, the crest-perpendicular length of the aerated breaking region (roller length) and wave direction are estimated and used to compute the wave energy dissipation rate. The resultant dissipation rate maps are analyzed over different time scales: peak wave period, infragravity wave period, and tidal wave period. For each time scale, spatial maps of wave breaking are used to characterize wave forcing in the surf zone for a variety of wave conditions. The following phenomena are examined: (1) wave dissipation rates over the bar (location of most intense breaking) have increased variance in infragravity wave frequencies, which are different from the peak frequency of the incoming wave field and different from the wave forcing variability at the shoreline, and (2) wave forcing has a wider spatial distribution during low tide than during high tide due to depth-limited breaking over the barred bathymetry. Future work will investigate the response of the variability in wave setup, longshore currents and rip currents, to the variability in wave forcing in the surf zone.

Evaluation of Planned Treatment Breaks During Radiation Therapy for Anal Cancer: Update of RTOG 92-08

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konski, Andre; Garcia, Miguel; John, Madhu

2008-09-01

Purpose: Radiation Therapy Oncology Group (RTOG) 92-08 began as a single arm, Phase II trial for patients with anal cancer consisting of radiation (RT) + 5-flourouracil + mitomycin-C with a mandatory 2-week break and was amended after completion to evaluate the same treatment regimen without a treatment break. Long-term efficacy and late toxicity reporting are the specific aims of this study. Methods and Materials: Survivals were estimated with the Kaplan-Meier method. Overall survival (OS) was compared with RTOG 87-04 with the log-rank test. Time to local failure, regional failure, locoregional failure (LRF), distant metastases, second primary, and colostomy failure weremore » estimated by the cumulative incidence method. LRF was compared with RTOG 87-04 using the Gray's test. Results: Forty-seven patients entered in the mandatory treatment break cohort. The study was reopened in 1995 to the no mandatory treatment break cohort completing accrual with 20 patients in 1996. Of 67 total patients, 1 patient in the mandatory treatment break portion of the study did not receive any protocol treatment and is excluded from analyses. After adjusting for tumor size, neither cohort showed a statistically significant difference in OS or LRF compared with the RTOG 87-04 mitomycin-C arm. No patient in either cohort experienced a Grade 3 or higher late toxicity. Conclusions: No statistically significant differences were seen in OS or LRF when compared to the mitomycin-C arm of RTOG 87-04, but the sample sizes for the mandatory break cohort and the no mandatory break cohort are small. Late toxicity was low and similar for the treatment cohorts.« less

Salient Features of Endonuclease Platforms for Therapeutic Genome Editing.

PubMed

Certo, Michael T; Morgan, Richard A

2016-03-01

Emerging gene-editing technologies are nearing a revolutionary phase in genetic medicine: precisely modifying or repairing causal genetic defects. This may include any number of DNA sequence manipulations, such as knocking out a deleterious gene, introducing a particular mutation, or directly repairing a defective sequence by site-specific recombination. All of these edits can currently be achieved via programmable rare-cutting endonucleases to create targeted DNA breaks that can engage and exploit endogenous DNA repair pathways to impart site-specific genetic changes. Over the past decade, several distinct technologies for introducing site-specific DNA breaks have been developed, yet the different biological origins of these gene-editing technologies bring along inherent differences in parameters that impact clinical implementation. This review aims to provide an accessible overview of the various endonuclease-based gene-editing platforms, highlighting the strengths and weakness of each with respect to therapeutic applications.

Salient Features of Endonuclease Platforms for Therapeutic Genome Editing

PubMed Central

Certo, Michael T; Morgan, Richard A

2016-01-01

Emerging gene-editing technologies are nearing a revolutionary phase in genetic medicine: precisely modifying or repairing causal genetic defects. This may include any number of DNA sequence manipulations, such as knocking out a deleterious gene, introducing a particular mutation, or directly repairing a defective sequence by site-specific recombination. All of these edits can currently be achieved via programmable rare-cutting endonucleases to create targeted DNA breaks that can engage and exploit endogenous DNA repair pathways to impart site-specific genetic changes. Over the past decade, several distinct technologies for introducing site-specific DNA breaks have been developed, yet the different biological origins of these gene-editing technologies bring along inherent differences in parameters that impact clinical implementation. This review aims to provide an accessible overview of the various endonuclease-based gene-editing platforms, highlighting the strengths and weakness of each with respect to therapeutic applications. PMID:26796671

Verbs in the lexicon: Why is hitting easier than breaking?

PubMed

McKoon, Gail; Love, Jessica

2011-11-01

Adult speakers use verbs in syntactically appropriate ways. For example, they know implicitly that the boy hit at the fence is acceptable but the boy broke at the fence is not. We suggest that this knowledge is lexically encoded in semantic decompositions. The decomposition for break verbs (e.g. crack, smash) is hypothesized to be more complex than that for hit verbs (e.g. kick, kiss). Specifically, the decomposition of a break verb denotes that "an entity changes state as the result of some external force" whereas the decomposition for a hit verb denotes only that "an entity potentially comes in contact with another entity." In this article, verbs of the two types were compared in a lexical decision experiment - Experiment 1 - and they were compared in sentence comprehension experiments with transitive sentences (e.g. the car hit the bicycle and the car broke the bicycle) - Experiments 2 and 3. In Experiment 1, processing times were shorter for the hit than the break verbs and in Experiments 2 and 3, processing times were shorter for the hit sentences than the break sentences, results that are in accord with the complexities of the postulated semantic decompositions.

Orthogonality-breaking sensing model based on the instantaneous Stokes vector and the Mueller calculus

NASA Astrophysics Data System (ADS)

Ortega-Quijano, Noé; Fade, Julien; Roche, Muriel; Parnet, François; Alouini, Mehdi

2016-04-01

Polarimetric sensing by orthogonality breaking has been recently proposed as an alternative technique for performing direct and fast polarimetric measurements using a specific dual-frequency dual-polarization (DFDP) source. Based on the instantaneous Stokes-Mueller formalism to describe the high-frequency evolution of the DFDP beam intensity, we thoroughly analyze the interaction of such a beam with birefringent, dichroic and depolarizing samples. This allows us to confirm that orthogonality breaking is produced by the sample diattenuation, whereas this technique is immune to both birefringence and diagonal depolarization. We further analyze the robustness of this technique when polarimetric sensing is performed through a birefringent waveguide, and the optimal DFDP source configuration for fiber-based endoscopic measurements is subsequently identified. Finally, we consider a stochastic depolarization model based on an ensemble of random linear diattenuators, which makes it possible to understand the progressive vanishing of the detected orthogonality breaking signal as the spatial heterogeneity of the sample increases, thus confirming the insensitivity of this method to diagonal depolarization. The fact that the orthogonality breaking signal is exclusively due to the sample dichroism is an advantageous feature for the precise decoupled characterization of such an anisotropic parameter in samples showing several simultaneous effects.

Dynamic decision making for dam-break emergency management - Part 1: Theoretical framework

NASA Astrophysics Data System (ADS)

Peng, M.; Zhang, L. M.

2013-02-01

An evacuation decision for dam breaks is a very serious issue. A late decision may lead to loss of lives and properties, but a very early evacuation will incur unnecessary expenses. This paper presents a risk-based framework of dynamic decision making for dam-break emergency management (DYDEM). The dam-break emergency management in both time scale and space scale is introduced first to define the dynamic decision problem. The probability of dam failure is taken as a stochastic process and estimated using a time-series analysis method. The flood consequences are taken as functions of warning time and evaluated with a human risk analysis model (HURAM) based on Bayesian networks. A decision criterion is suggested to decide whether to evacuate the population at risk (PAR) or to delay the decision. The optimum time for evacuating the PAR is obtained by minimizing the expected total loss, which integrates the time-related probabilities and flood consequences. When a delayed decision is chosen, the decision making can be updated with available new information. A specific dam-break case study is presented in a companion paper to illustrate the application of this framework to complex dam-breaching problems.

The role of the non-homologous end-joining pathway in lymphocyte development.

PubMed

Rooney, Sean; Chaudhuri, Jayanta; Alt, Frederick W

2004-08-01

One of the most toxic insults a cell can incur is a disruption of its linear DNA in the form of a double-strand break (DSB). Left unrepaired, or repaired improperly, these lesions can result in cell death or neoplastic transformation. Despite these dangers, lymphoid cells purposely introduce DSBs into their genome to maximize the diversity and effector functions of their antigen receptor genes. While the generation of breaks requires distinct lymphoid-specific factors, their resolution requires various ubiquitously expressed DNA-repair proteins, known collectively as the non-homologous end-joining pathway. In this review, we discuss the factors that constitute this pathway as well as the evidence of their involvement in two lymphoid-specific DNA recombination events.

Thermodynamic properties of Dynes superconductors

NASA Astrophysics Data System (ADS)

Herman, František; Hlubina, Richard

2018-01-01

The tunneling density of states in dirty s -wave superconductors is often well described by the phenomenological Dynes formula. Recently we have shown that this formula can be derived, within the coherent potential approximation, for superconductors with simultaneously present pair-conserving and pair-breaking impurity scattering. Here we demonstrate that the theory of such so-called Dynes superconductors is thermodynamically consistent. We calculate the specific heat and critical field of the Dynes superconductors, and we show that their gap parameter, specific heat, critical field, and penetration depth exhibit power-law scaling with temperature in the low-temperature limit. We also show that in the vicinity of a coupling-constant-controlled superconductor to normal metal transition, the Homes law is replaced by a different, pair-breaking-dominated scaling law.

Symmetry Breaking in the Supramolecular Gels of an Achiral Gelator Exclusively Driven by π-π Stacking.

PubMed

Shen, Zhaocun; Jiang, Yuqian; Wang, Tianyu; Liu, Minghua

2015-12-30

Supramolecular symmetry breaking, in which chiral assemblies with imbalanced right- and left-handedness emerge from achiral molecular building blocks, has been achieved in the organogels of a C3-symmetric molecule only via π-π stacking. Specifically, an achiral C3-symmetric benzene-1,3,5-tricarboxylate substituted with methyl cinnamate through ester bond was found to form organogels in various organic solvents. More interestingly, when gels formed in cyclohexane, symmetry breaking occurred; i.e., optically active organogels together with the helical nanofibers with predominant handedness were obtained. Furthermore, the stochastically appeared imbalanced helicity could be driven to desired handedness by utilizing slight chiral solvents such as (R)- or (S)-terpinen-4-ol. Remarkably, the handedness of supramolecular assemblies thus formed could be kept even when the chiral solvents were removed. For the first time, we show that symmetry breaking can occur in supramolecular gel system driven exclusively through π-π stacking.

Review of high fidelity imaging spectrometer design for remote sensing

NASA Astrophysics Data System (ADS)

Mouroulis, Pantazis; Green, Robert O.

2018-04-01

We review the design and assessment techniques that underlie a number of successfully deployed space and airborne imaging spectrometers that have been demonstrated to achieve demanding specifications in terms of throughput and response uniformity. The principles are illustrated with telescope designs as well as spectrometer examples from the Offner and Dyson families. We also show how the design space can be extended with the use of freeform surfaces and provide additional design examples with grating as well as prism dispersive elements.

Molecular Mechanisms of Neuroplasticity: An Expanding Universe.

PubMed

Gulyaeva, N V

2017-03-01

Biochemical processes in synapses and other neuronal compartments underlie neuroplasticity (functional and structural alterations in the brain enabling adaptation to the environment, learning, memory, as well as rehabilitation after brain injury). This basic molecular level of brain plasticity covers numerous specific proteins (enzymes, receptors, structural proteins, etc.) participating in many coordinated and interacting signal and metabolic processes, their modulation forming a molecular basis for brain plasticity. The articles in this issue are focused on different "hot points" in the research area of biochemical mechanisms supporting neuroplasticity.

Measurements of Two-Phase Suspended Sediment Transport in Breaking Waves Using Volumetric Three-Component Velocimetry

NASA Astrophysics Data System (ADS)

Ting, F. C. K.; LeClaire, P.

2016-02-01

Understanding the mechanisms of sediment pickup and distribution in breaking waves is important for modeling sediment transport in the surf zone. Previous studies were mostly concerned with bulk sediment transport under specific wave conditions. The distribution of suspended sediments in breaking waves had not been measured together with coherent flow structures. In this study, two-phase flow measurements were obtained under a train of plunging regular waves on a plane slope using the volumetric three-component velocimetry (V3V) technique. The measurements captured the motions of sediment particles simultaneously with the three-component, three-dimensional (3C3D) velocity fields of turbulent coherent structures (large eddies) induced by breaking waves. Sediment particles (solid glass spheres diameter 0.125 to 0.15 mm, specific gravity 2.5) were separated from fluid tracers (mean diameter 13 µm, specific gravity 1.3) based on a combination of particle spot size and brightness in the two-phase images. The interactions between the large eddies and glass spheres were investigated for plunger vortices generated at incipient breaking and for splash-up vortices generated at the second plunge point. The measured data show that large eddies impinging on the bottom was the primary mechanism which lift sediment particles into suspension and momentarily increased near-bed suspended sediment concentration. Although eddy impingement events were sporadic in space and time, the distributions of suspended sediments in the large eddies were not uniform. High suspended sediment concentration and vertical sediment flux were found in the wall-jet region where the impinging flow was deflected outward and upward. Sediment particles were also trapped and carried around by counter-rotating vortices (Figure 1). Suspended sediment concentration was significantly lower in the impingement region where the fluid velocity was downward, even though turbulent kinetic energy in the down flow was very high. These results suggest that vertical velocity or turbulent shear stress may be a better parameter for predicting sediment pick-up rate than turbulent kinetic energy. It was also found that splash-up vortices enhanced onshore transport relative to the condition when no vortex impinged on the bottom.

Splicing stimulates siRNA formation at Drosophila DNA double-strand breaks

PubMed Central

Merk, Karin; Breinig, Marco; Böttcher, Romy; Krebs, Stefan; Blum, Helmut; Boutros, Michael

2017-01-01

DNA double-strand breaks trigger the production of locus-derived siRNAs in fruit flies, human cells and plants. At least in flies, their biogenesis depends on active transcription running towards the break. Since siRNAs derive from a double-stranded RNA precursor, a major question is how broken DNA ends can generate matching sense and antisense transcripts. We performed a genome-wide RNAi-screen in cultured Drosophila cells, which revealed that in addition to DNA repair factors, many spliceosome components are required for efficient siRNA generation. We validated this observation through site-specific DNA cleavage with CRISPR-cas9 followed by deep sequencing of small RNAs. DNA breaks in intron-less genes or upstream of a gene’s first intron did not efficiently trigger siRNA production. When DNA double-strand breaks were induced downstream of an intron, however, this led to robust siRNA generation. Furthermore, a downstream break slowed down splicing of the upstream intron and a detailed analysis of siRNA coverage at the targeted locus revealed that unspliced pre-mRNA contributes the sense strand to the siRNA precursor. Since splicing factors are stimulating the response but unspliced transcripts are entering the siRNA biogenesis, the spliceosome is apparently stalled in a pre-catalytic state and serves as a signaling hub. We conclude that convergent transcription at DNA breaks is stimulated by a splicing dependent control process. The resulting double-stranded RNA is converted into siRNAs that instruct the degradation of cognate mRNAs. In addition to a potential role in DNA repair, the break-induced transcription may thus be a means to cull improper RNAs from the transcriptome of Drosophila melanogaster. Since the splicing factors identified in our screen also stimulated siRNA production from high copy transgenes, it is possible that this surveillance mechanism serves in genome defense beyond DNA double-strand breaks. PMID:28628606

A new phase transformation path from nanodiamond to new-diamond via an intermediate carbon onion

NASA Astrophysics Data System (ADS)

Xiao, J.; Li, J. L.; Liu, P.; Yang, G. W.

2014-11-01

The investigation of carbon allotropes such as graphite, diamond, fullerenes, nanotubes and carbon onions and mechanisms that underlie their mutual phase transformation is a long-standing problem of great fundamental importance. New diamond (n-diamond) is a novel metastable phase of carbon with a face-centered cubic structure; it is called ``new diamond'' because many reflections in its electron diffraction pattern are similar to those of diamond. However, producing n-diamond from raw carbon materials has so far been challenging due to n-diamond's higher formation energy than that of diamond. Here, we, for the first time, demonstrate a new phase transformation path from nanodiamond to n-diamond via an intermediate carbon onion in the unique process of laser ablation in water, and establish that water plays a crucial role in the formation of n-diamond. When a laser irradiates colloidal suspensions of nanodiamonds at ambient pressure and room temperature, nanodiamonds are first transformed into carbon onions serving as an intermediate phase, and sequentially carbon onions are transformed into n-diamonds driven by the laser-induced high temperature and high pressure from the carbon onion as a nanoscaled temperature and pressure cell upon the process of laser irradiation in a liquid. This phase transformation not only provides new insight into the physical mechanism involved, but also offers one suitable opportunity for breaking controllable pathways between n-diamond and carbon allotropes such as diamond and carbon onions.The investigation of carbon allotropes such as graphite, diamond, fullerenes, nanotubes and carbon onions and mechanisms that underlie their mutual phase transformation is a long-standing problem of great fundamental importance. New diamond (n-diamond) is a novel metastable phase of carbon with a face-centered cubic structure; it is called ``new diamond'' because many reflections in its electron diffraction pattern are similar to those of diamond. However, producing n-diamond from raw carbon materials has so far been challenging due to n-diamond's higher formation energy than that of diamond. Here, we, for the first time, demonstrate a new phase transformation path from nanodiamond to n-diamond via an intermediate carbon onion in the unique process of laser ablation in water, and establish that water plays a crucial role in the formation of n-diamond. When a laser irradiates colloidal suspensions of nanodiamonds at ambient pressure and room temperature, nanodiamonds are first transformed into carbon onions serving as an intermediate phase, and sequentially carbon onions are transformed into n-diamonds driven by the laser-induced high temperature and high pressure from the carbon onion as a nanoscaled temperature and pressure cell upon the process of laser irradiation in a liquid. This phase transformation not only provides new insight into the physical mechanism involved, but also offers one suitable opportunity for breaking controllable pathways between n-diamond and carbon allotropes such as diamond and carbon onions. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05246c

Perceptions of Rule-Breaking Related to Marine Ecosystem Health

PubMed Central

Slater, Matthew J.; Mgaya, Yunus D.; Stead, Selina M.

2014-01-01

Finding effective solutions to manage marine resources is high on political and conservation agendas worldwide. This is made more urgent by the rate of increase in the human population and concomitant resource pressures in coastal areas. This paper links empirical socio-economic data about perceptions of marine resource health to the breaking of marine management rules, using fisheries as a case study. The relationship between perceived rule-breaking (non-compliance with regulations controlling fishing) and perceived health of inshore marine environments was investigated through face-to-face interviews with 299 heads of households in three Tanzanian coastal communities in November and December 2011. Awareness of rules controlling fishing activity was high among all respondents. Fishers were able to describe more specific rules controlling fishing practices than non-fishers (t = 3.5, df = 297, p<0.01). Perceived breaking of fishing regulations was reported by nearly half of all respondents, saying “some” (32% of responses) or “most” (15% of responses) people break fishing rules. Ordinal regression modelling revealed a significant linkage (z = −3.44, p<0.001) in the relationship between respondents' perceptions of deteriorating marine health and their perception of increased rule-breaking. In this paper, inferences from an empirical study are used to identify and argue the potential for using perceptions of ecosystem health and level of rule-breaking as a means to guide management measures. When considering different management options (e.g. Marine Protected Areas), policy makers are advised to take account of and utilise likely egoistic or altruistic decision-making factors used by fishers to determine their marine activities. PMID:24586558

Perceptions of rule-breaking related to marine ecosystem health.

PubMed

Slater, Matthew J; Mgaya, Yunus D; Stead, Selina M

2014-01-01

Finding effective solutions to manage marine resources is high on political and conservation agendas worldwide. This is made more urgent by the rate of increase in the human population and concomitant resource pressures in coastal areas. This paper links empirical socio-economic data about perceptions of marine resource health to the breaking of marine management rules, using fisheries as a case study. The relationship between perceived rule-breaking (non-compliance with regulations controlling fishing) and perceived health of inshore marine environments was investigated through face-to-face interviews with 299 heads of households in three Tanzanian coastal communities in November and December 2011. Awareness of rules controlling fishing activity was high among all respondents. Fishers were able to describe more specific rules controlling fishing practices than non-fishers (t = 3.5, df = 297, p<0.01). Perceived breaking of fishing regulations was reported by nearly half of all respondents, saying "some" (32% of responses) or "most" (15% of responses) people break fishing rules. Ordinal regression modelling revealed a significant linkage (z= -3.44, p<0.001) in the relationship between respondents' perceptions of deteriorating marine health and their perception of increased rule-breaking. In this paper, inferences from an empirical study are used to identify and argue the potential for using perceptions of ecosystem health and level of rule-breaking as a means to guide management measures. When considering different management options (e.g. Marine Protected Areas), policy makers are advised to take account of and utilise likely egoistic or altruistic decision-making factors used by fishers to determine their marine activities.

Spring Break versus Spring Broken: Predictive Utility of Spring Break Alcohol Intentions and Willingness at Varying Levels of Extremity

PubMed Central

Litt, Dana M.; Lewis, Melissa A.; Patrick, Megan E.; Rodriguez, Lindsey; Neighbors, Clayton; Kaysen, Debra L.

2013-01-01

Objective Within the domain of risk-related behavior, many times the decision to engage is not a product of premeditation or intention. The Prototype Willingness model was created to capture and explain the unintended element of risk behavior. The present study aimed to evaluate the importance of willingness versus intention, two important constructs within the Prototype Willingness model, in relation to Spring Break drinking behavior when assessed at both high and low extremities. Method College undergraduates (N = 275) completed questionnaires prior to Spring Break regarding their anticipated Spring Break activities. Willingness and intention were assessed for different levels of risk. Specifically, participants indicated the extent to which they intended to (a) get drunk and (b) drink enough to black out or pass out; and the extent to which they were willing to (a) get drunk and (b) drink enough to black out or pass out. When classes resumed following Spring Break, the students indicated the extent to which they actually (a) got drunk and (b) drank enough to black out or pass out. Results Results demonstrated that when the health-related risk was lower (i.e., getting drunk), intention was a stronger predictor of behavior than was willingness. However, as the level of risk increased (i.e., getting drunk enough to black out or pass out), willingness more strongly predicted behavior. Conclusion The present study suggests that willingness and intentions differentially predict Spring Break alcohol-related behavior depending on the extremity of behavior in question. Implications regarding alcohol interventions are discussed. PMID:23404667

Dynamic and diverse sugar signaling

PubMed Central

Li, Lei; Sheen, Jen

2016-01-01

Sugars fuel life and exert numerous regulatory actions that are fundamental to all life forms. There are two principal mechanisms underlie sugar “perception and signal transduction” in biological systems. Direct sensing and signaling is triggered via sugar-binding sensors with a broad range of affinity and specificity, whereas sugar-derived bioenergetic molecules and metabolites modulate signaling proteins and indirectly relay sugar signals. This review discusses the emerging sugar signals and potential sugar sensors discovered in plant systems. The findings leading to informative understanding of physiological regulation by sugars are considered and assessed. Comparative transcriptome analyses highlight the primary and dynamic sugar responses and reveal the convergent and specific regulators of key biological processes in the sugar-signaling network. PMID:27423125

DOE Office of Scientific and Technical Information (OSTI.GOV)

FUHRMANN,M.SULLIVAN,T.

The objective of this report is to discuss the degree of sorption and desorption of {sup 137}Cs and {sup 60}Co that may be associated with the granite bedrock and the ''popcorn'' cement drain system that underlie the Maine Yankee Containment Foundation. The purpose is to estimate how much retardation of these two radionuclides takes place in groundwater that flows in the near-field of the Containment Foundation, specifically with respect to contamination originating at the PAB Test Pit. Specific concerns revolve around the potential for the contamination originating near the PAB to create a radioactive dose to a hypothetical ''resident farmer''more » using a well intercepting this water to exceed 4 millirems/yr.« less

Geographic variations in mortality from motor vehicle crashes in Taiwan.

PubMed

Yang, C Y; Chiu, J F; Lin, M C; Cheng, M F

1997-07-01

Mortality from motor vehicle crashes within five urbanization categories in Taiwan between 1981 and 1990 was investigated. Sex-specific standardized mortality ratios (SMRs) were calculated within each urbanization category for motor vehicle crash deaths. Most urban areas demonstrated lower SMRs for both males and females. In contrast, most rural areas exhibited higher SMRs for both males and females. Both males and females demonstrated a significant linear relationship between decreasing urbanization and increasing SMRs for motor vehicle crash mortality. A variety of factors may underlie the inverse correlation between SMRs for motor vehicle crashes and urbanization category. These data are most useful in generating hypotheses for further studies to define specific etiological factors operating within urbanization categories.

Childhood tuberculosis and malnutrition.

PubMed

Jaganath, Devan; Mupere, Ezekiel

2012-12-15

Despite the burden of both malnutrition and tuberculosis in children worldwide, there are few studies on the mechanisms that underlie this relationship. From available research, it appears that malnutrition is a predictor of tuberculosis disease and is associated with worse outcomes. This is supported through several lines of evidence, including the role of vitamin D receptor genotypes, malnutrition's effects on immune development, respiratory infections among malnourished children, and limited work specifically on pediatric tuberculosis and malnutrition. Nutritional supplementation has yet to suggest significant benefits on the course of tuberculosis in children. There is a critical need for research on childhood tuberculosis, specifically on how nutritional status affects the risk and progression of tuberculosis and whether nutritional supplementation improves clinical outcomes or prevents disease.

Synaptic Mechanisms of Memory Consolidation during Sleep Slow Oscillations

PubMed Central

Wei, Yina; Krishnan, Giri P.

2016-01-01

Sleep is critical for regulation of synaptic efficacy, memories, and learning. However, the underlying mechanisms of how sleep rhythms contribute to consolidating memories acquired during wakefulness remain unclear. Here we studied the role of slow oscillations, 0.2–1 Hz rhythmic transitions between Up and Down states during stage 3/4 sleep, on dynamics of synaptic connectivity in the thalamocortical network model implementing spike-timing-dependent synaptic plasticity. We found that the spatiotemporal pattern of Up-state propagation determines the changes of synaptic strengths between neurons. Furthermore, an external input, mimicking hippocampal ripples, delivered to the cortical network results in input-specific changes of synaptic weights, which persisted after stimulation was removed. These synaptic changes promoted replay of specific firing sequences of the cortical neurons. Our study proposes a neuronal mechanism on how an interaction between hippocampal input, such as mediated by sharp wave-ripple events, cortical slow oscillations, and synaptic plasticity, may lead to consolidation of memories through preferential replay of cortical cell spike sequences during slow-wave sleep. SIGNIFICANCE STATEMENT Sleep is critical for memory and learning. Replay during sleep of temporally ordered spike sequences related to a recent experience was proposed to be a neuronal substrate of memory consolidation. However, specific mechanisms of replay or how spike sequence replay leads to synaptic changes that underlie memory consolidation are still poorly understood. Here we used a detailed computational model of the thalamocortical system to report that interaction between slow cortical oscillations and synaptic plasticity during deep sleep can underlie mapping hippocampal memory traces to persistent cortical representation. This study provided, for the first time, a mechanistic explanation of how slow-wave sleep may promote consolidation of recent memory events. PMID:27076422

Referent control and motor equivalence of reaching from standing

PubMed Central

Tomita, Yosuke; Feldman, Anatol G.

2016-01-01

Motor actions may result from central changes in the referent body configuration, defined as the body posture at which muscles begin to be activated or deactivated. The actual body configuration deviates from the referent configuration, particularly because of body inertia and environmental forces. Within these constraints, the system tends to minimize the difference between these configurations. For pointing movement, this strategy can be expressed as the tendency to minimize the difference between the referent trajectory (RT) and actual trajectory (QT) of the effector (hand). This process may underlie motor equivalent behavior that maintains the pointing trajectory regardless of the number of body segments involved. We tested the hypothesis that the minimization process is used to produce pointing in standing subjects. With eyes closed, 10 subjects reached from a standing position to a remembered target located beyond arm length. In randomly chosen trials, hip flexion was unexpectedly prevented, forcing subjects to take a step during pointing to prevent falling. The task was repeated when subjects were instructed to intentionally take a step during pointing. In most cases, reaching accuracy and trajectory curvature were preserved due to adaptive condition-specific changes in interjoint coordination. Results suggest that referent control and the minimization process associated with it may underlie motor equivalence in pointing. NEW & NOTEWORTHY Motor actions may result from minimization of the deflection of the actual body configuration from the centrally specified referent body configuration, in the limits of neuromuscular and environmental constraints. The minimization process may maintain reaching trajectory and accuracy regardless of the number of body segments involved (motor equivalence), as confirmed in this study of reaching from standing in young healthy individuals. Results suggest that the referent control process may underlie motor equivalence in reaching. PMID:27784802

Blockbuster Ideas: Activities for Breaking Up Block Periods.

ERIC Educational Resources Information Center

Bohince, Judy

1996-01-01

Describes how to approach block scheduling of science classes. Discusses the planning process, specific activities that work well in longer science classes, and techniques for motivating students. (DDR)

Genetics Home Reference: generalized arterial calcification of infancy

MedlinePlus

... helps break down a molecule called adenosine triphosphate (ATP), specifically when it is found outside the cell (extracellular). Extracellular ATP is quickly broken down into other molecules called ...

Response of jammed packings to thermal fluctuations

NASA Astrophysics Data System (ADS)

Wu, Qikai; Bertrand, Thibault; Shattuck, Mark D.; O'Hern, Corey S.

2017-12-01

We focus on the response of mechanically stable (MS) packings of frictionless, bidisperse disks to thermal fluctuations, with the aim of quantifying how nonlinearities affect system properties at finite temperature. In contrast, numerous prior studies characterized the structural and mechanical properties of MS packings of frictionless spherical particles at zero temperature. Packings of disks with purely repulsive contact interactions possess two main types of nonlinearities, one from the form of the interaction potential (e.g., either linear or Hertzian spring interactions) and one from the breaking (or forming) of interparticle contacts. To identify the temperature regime at which the contact-breaking nonlinearities begin to contribute, we first calculated the minimum temperatures Tc b required to break a single contact in the MS packing for both single- and multiple-eigenmode perturbations of the T =0 MS packing. We find that the temperature required to break a single contact for equal velocity-amplitude perturbations involving all eigenmodes approaches the minimum value obtained for a perturbation in the direction connecting disk pairs with the smallest overlap. We then studied deviations in the constant volume specific heat C¯V and deviations of the average disk positions Δ r from their T =0 values in the temperature regime TC ¯V100 for linear spring interactions is independent of system size. This result emphasizes that contact-breaking nonlinearities are dominant over form nonlinearities in the low-temperature range Tc b

Value Contestations in Development Intervention: Community Development and Sustainable Livelihoods Approaches.

ERIC Educational Resources Information Center

Arce, Alberto

2003-01-01

Both community development and sustainable livelihood approaches ignore value contestations that underlie people's interests and experiences. A case from Bolivia demonstrates that local values, social relations, actions, and language strategies must underlie policy and method in development. (Contains 28 references.) (SK)

Lighten Up!

ERIC Educational Resources Information Center

Fleming, Colette

2001-01-01

Discusses how schools can reduce the occurances of physical injury, vandalism, and break-ins by properly lighting school areas. Several examples of lighting strategies are highlighted, including determining proper illumination levels for specific areas. (GR)

Analysis of unmitigated large break loss of coolant accidents using MELCOR code

NASA Astrophysics Data System (ADS)

Pescarini, M.; Mascari, F.; Mostacci, D.; De Rosa, F.; Lombardo, C.; Giannetti, F.

2017-11-01

In the framework of severe accident research activity developed by ENEA, a MELCOR nodalization of a generic Pressurized Water Reactor of 900 MWe has been developed. The aim of this paper is to present the analysis of MELCOR code calculations concerning two independent unmitigated large break loss of coolant accident transients, occurring in the cited type of reactor. In particular, the analysis and comparison between the transients initiated by an unmitigated double-ended cold leg rupture and an unmitigated double-ended hot leg rupture in the loop 1 of the primary cooling system is presented herein. This activity has been performed focusing specifically on the in-vessel phenomenology that characterizes this kind of accidents. The analysis of the thermal-hydraulic transient phenomena and the core degradation phenomena is therefore here presented. The analysis of the calculated data shows the capability of the code to reproduce the phenomena typical of these transients and permits their phenomenological study. A first sequence of main events is here presented and shows that the cold leg break transient results faster than the hot leg break transient because of the position of the break. Further analyses are in progress to quantitatively assess the results of the code nodalization for accident management strategy definition and fission product source term evaluation.

Large-mutation spectra induced at hemizygous loci by low-LET radiation: evidence for intrachromosomal proximity effects

NASA Technical Reports Server (NTRS)

Costes, S.; Sachs, R.; Hlatky, L.; Vannais, D.; Waldren, C.; Fouladi, B.; Chatterjee, A. (Principal Investigator)

2001-01-01

A mathematical model is used to analyze mutant spectra for large mutations induced by low-LET radiation. The model equations are based mainly on two-break misrejoining that leads to deletions or translocations. It is assumed, as a working hypothesis, that the initial damage induced by low-LET radiation is located randomly in the genome. Specifically, we analyzed data for two hemizygous loci: CD59- mutants, mainly very large-scale deletions (>3 Mbp), in human-hamster hybrid cells, and data from the literature on those HPRT- mutants which involve at least deletion of the whole gene, and often of additional flanking markers (approximately 50-kbp to approximately 4.4-Mbp deletions). For five data sets, we estimated f, the probability that two given breaks on the same chromosome will misrejoin to make a deletion, as a function of the separation between the breaks. We found that f is larger for nearby breaks than for breaks that are more widely separated; i.e., there is a "proximity effect". For acute irradiation, the values of f determined from the data are consistent with the corresponding break misrejoining parameters found previously in quantitative modeling of chromosome aberrations. The value of f was somewhat smaller for protracted irradiation than for acute irradiation at a given total dose; i.e., the mutation data show a decrease that was smaller than expected for dose protraction by fractionation or low dose rate.

Incoherent transport for phases that spontaneously break translations

NASA Astrophysics Data System (ADS)

Donos, Aristomenis; Gauntlett, Jerome P.; Griffin, Tom; Ziogas, Vaios

2018-04-01

We consider phases of matter at finite charge density which spontaneously break spatial translations. Without taking a hydrodynamic limit we identify a boost invariant incoherent current operator. We also derive expressions for the small frequency behaviour of the thermoelectric conductivities generalising those that have been derived in a translationally invariant context. Within holographic constructions we show that the DC conductivity for the incoherent current can be obtained from a solution to a Stokes flow for an auxiliary fluid on the black hole horizon combined with specific thermodynamic quantities associated with the equilibrium black hole solutions.

46 CFR 160.060-3a - Materials-Dee ring and snap hook assemblies and other instruments of closure for buoyant vests.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Specification for a Buoyant Vest, Unicellular Polyethylene Foam, Adult and Child § 160... and 115 pounds for a child size for 10 minutes at ambient temperatures without breaking or distorting...

Breaking the Discrepancy Code: A Meta-Analysis of the Specific Learning Disability Literature

ERIC Educational Resources Information Center

Bachmeier, Randy J.

2009-01-01

Previous "selective" meta-analyses of the literature relating to the IQ-achievement discrepancy model of specific learning disability identification have concluded that "underachieving" and "low-achieving" poor readers do not differ in any educationally meaningful way. Underachievers are those poor readers who qualify as learning disabled using an…

Exploring non-holomorphic soft terms in the framework of gauge mediated supersymmetry breaking

NASA Astrophysics Data System (ADS)

Chattopadhyay, Utpal; Das, Debottam; Mukherjee, Samadrita

2018-01-01

It is known that in the absence of a gauge singlet field, a specific class of supersymmetry (SUSY) breaking non-holomorphic (NH) terms can be soft breaking in nature so that they may be considered along with the Minimal Supersymmetric Standard Model (MSSM) and beyond. There have been studies related to these terms in minimal supergravity based models. Consideration of an F-type SUSY breaking scenario in the hidden sector with two chiral superfields however showed Planck scale suppression of such terms. In an unbiased point of view for the sources of SUSY breaking, the NH terms in a phenomenological MSSM (pMSSM) type of analysis showed a possibility of a large SUSY contribution to muon g - 2, a reasonable amount of corrections to the Higgs boson mass and a drastic reduction of the electroweak fine-tuning for a higgsino dominated {\\tilde{χ}}_1^0 in some regions of parameter space. We first investigate here the effects of the NH terms in a low scale SUSY breaking scenario. In our analysis with minimal gauge mediated supersymmetry breaking (mGMSB) we probe how far the results can be compared with the previous pMSSM plus NH terms based study. We particularly analyze the Higgs, stop and the electroweakino sectors focusing on a higgsino dominated {\\tilde{χ}}_1^0 and {\\tilde{χ}}_1^{± } , a feature typically different from what appears in mGMSB. The effect of a limited degree of RG evolutions and vanishing of the trilinear coupling terms at the messenger scale can be overcome by choosing a non-minimal GMSB scenario, such as one with a matter-messenger interaction.

Segmental duplications and evolutionary plasticity at tumor chromosome break-prone regions

PubMed Central

Darai-Ramqvist, Eva; Sandlund, Agneta; Müller, Stefan; Klein, George; Imreh, Stefan; Kost-Alimova, Maria

2008-01-01

We have previously found that the borders of evolutionarily conserved chromosomal regions often coincide with tumor-associated deletion breakpoints within human 3p12-p22. Moreover, a detailed analysis of a frequently deleted region at 3p21.3 (CER1) showed associations between tumor breaks and gene duplications. We now report on the analysis of 54 chromosome 3 breaks by multipoint FISH (mpFISH) in 10 carcinoma-derived cell lines. The centromeric region was broken in five lines. In lines with highly complex karyotypes, breaks were clustered near known fragile sites, FRA3B, FRA3C, and FRA3D (three lines), and in two other regions: 3p12.3-p13 (∼75 Mb position) and 3q21.3-q22.1 (∼130 Mb position) (six lines). All locations are shown based on NCBI Build 36.1 human genome sequence. The last two regions participated in three of four chromosome 3 inversions during primate evolution. Regions at 75, 127, and 131 Mb positions carry a large (∼250 kb) segmental duplication (tumor break-prone segmental duplication [TBSD]). TBSD homologous sequences were found at 15 sites on different chromosomes. They were located within bands frequently involved in carcinoma-associated breaks. Thirteen of them have been involved in inversions during primate evolution; 10 were reused by breaks during mammalian evolution; 14 showed copy number polymorphism in man. TBSD sites showed an increase in satellite repeats, retrotransposed sequences, and other segmental duplications. We propose that the instability of these sites stems from specific organization of the chromosomal region, associated with location at a boundary between different CG-content isochores and with the presence of TBSDs and “instability elements,” including satellite repeats and retroviral sequences. PMID:18230801

Segmental duplications and evolutionary plasticity at tumor chromosome break-prone regions.

PubMed

Darai-Ramqvist, Eva; Sandlund, Agneta; Müller, Stefan; Klein, George; Imreh, Stefan; Kost-Alimova, Maria

2008-03-01

We have previously found that the borders of evolutionarily conserved chromosomal regions often coincide with tumor-associated deletion breakpoints within human 3p12-p22. Moreover, a detailed analysis of a frequently deleted region at 3p21.3 (CER1) showed associations between tumor breaks and gene duplications. We now report on the analysis of 54 chromosome 3 breaks by multipoint FISH (mpFISH) in 10 carcinoma-derived cell lines. The centromeric region was broken in five lines. In lines with highly complex karyotypes, breaks were clustered near known fragile sites, FRA3B, FRA3C, and FRA3D (three lines), and in two other regions: 3p12.3-p13 ( approximately 75 Mb position) and 3q21.3-q22.1 ( approximately 130 Mb position) (six lines). All locations are shown based on NCBI Build 36.1 human genome sequence. The last two regions participated in three of four chromosome 3 inversions during primate evolution. Regions at 75, 127, and 131 Mb positions carry a large ( approximately 250 kb) segmental duplication (tumor break-prone segmental duplication [TBSD]). TBSD homologous sequences were found at 15 sites on different chromosomes. They were located within bands frequently involved in carcinoma-associated breaks. Thirteen of them have been involved in inversions during primate evolution; 10 were reused by breaks during mammalian evolution; 14 showed copy number polymorphism in man. TBSD sites showed an increase in satellite repeats, retrotransposed sequences, and other segmental duplications. We propose that the instability of these sites stems from specific organization of the chromosomal region, associated with location at a boundary between different CG-content isochores and with the presence of TBSDs and "instability elements," including satellite repeats and retroviral sequences.

Overview of Social Cognitive Dysfunctions in Rare Developmental Syndromes With Psychiatric Phenotype

PubMed Central

Morel, Aurore; Peyroux, Elodie; Leleu, Arnaud; Favre, Emilie; Franck, Nicolas; Demily, Caroline

2018-01-01

Rare neurodevelopmental syndromes often present social cognitive deficits that may underlie difficulties in social interactions and increase the risk of psychosis or autism spectrum disorders. However, little is known regarding the specificities of social cognitive impairment across syndromes while it remains a major challenge for the care. Our review provides an overview of social cognitive dysfunctions in rare diseases associated with psychiatric symptoms (with a prevalence estimated between 1 in 1,200 and 1 in 25,000 live births: 22q11.2 deletion syndrome, Angelman syndrome, Fragile X syndrome, Klinefelter syndrome, Prader–Willi syndrome, Rett syndrome, Smith–Magenis syndrome, Turner syndrome, and Williams syndrome) and shed some light on the specific mechanisms that may underlie these skills in each clinical presentation. We first detail the different processes included in the generic expression “social cognition” before summarizing the genotype, psychiatric phenotype, and non-social cognitive profile in each syndrome. Then, we offer a systematic review of the social cognitive abilities and the disturbed mechanisms they are likely associated with. We followed the PRISMA process, including the definition of the relevant search terms, the selection of studies based on clear inclusion, and exclusion criteria and the quality appraisal of papers. We finally provide insights that may have considerable influence on the development of adapted therapeutic interventions such as social cognitive training (SCT) therapies specifically designed to target the psychiatric phenotype. The results of this review suggest that social cognition impairments share some similarities across syndromes. We propose that social cognitive impairments are strongly involved in behavioral symptoms regardless of the overall cognitive level measured by intelligence quotient. Better understanding the mechanisms underlying impaired social cognition may lead to adapt therapeutic interventions. The studies targeting social cognition processes offer new thoughts about the development of specific cognitive training programs, as they highlight the importance of connecting neurocognitive and SCT techniques. PMID:29774207

New French Regulation for NPPs and Code Consequences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Faidy, Claude

2006-07-01

On December 2005, the French regulator issued a new regulation for French nuclear power plants, in particular for pressure equipment (PE). This regulation need first to agree with non-nuclear PE regulation and add to that some specific requirements, in particular radiation protection requirements. Different advantages are in these proposal, it's more qualitative risk oriented and it's an important link with non-nuclear industry. Only few components are nuclear specific. But, the general philosophy of the existing Codes (RCC-M [15], KTA [16] or ASME [17]) have to be improved. For foreign Codes, it's plan to define the differences in the user specifications.more » In parallel to that, a new safety classification has been developed by French utility. The consequences is the need to cross all these specifications to define a minimum quality level for each components or systems. In the same time a new concept has been developed to replace the well known 'Leak Before Break methodology': the 'Break Exclusion' methodology. This paper will summarize the key aspects of these different topics. (authors)« less

Nonlinearity in cytoplasm viscosity can generate an essential symmetry breaking in cellular behaviors.

PubMed

Tachikawa, Masashi; Mochizuki, Atsushi

2015-01-07

The cytoplasms of ameboid cells are nonlinearly viscous. The cell controls this viscosity by modulating the amount, localization and interactions of bio-polymers. Here we investigated how the nonlinearity infers the cellular behaviors and whether nonlinearity-specific behaviors exist. We modeled the developed plasmodium of the slime mold Physarum polycephalum as a network of branching tubes and examined the linear and nonlinear viscous cytoplasm flows in the tubes. We found that the nonlinearity in the cytoplasm׳s viscosity induces a novel type of symmetry breaking in the protoplasmic flow. We also show that symmetry breaking can play an important role in adaptive behaviors, namely, connection of behavioral modes implemented on different time scales and transportation of molecular signals from the front to the rear of the cell during cellular locomotion. Copyright © 2014 Elsevier Ltd. All rights reserved.

The early use of break-bone fever (Quebranta huesos, 1771) and dengue (1801) in Spanish.

PubMed

Rigau-Pérez, J G

1998-08-01

The appellation of break-bone fever for dengue is attributed to the popular name given to the disease in the first described epidemic of an illness that is clinically compatible with dengue in Philadelphia in 1780. The origin of the word dengue as the name of an illness is currently attributed to the Swahili phrase Ka dinga pepo, thought to have crossed from Africa to the Caribbean in 1827; in Cuba this phrase was popularly identified with the Spanish word dengue. This article presents documents from Spanish archives that indicate the use of quebranta huesos (break-bone) by a physician in Puerto Rico to describe a febrile illness in 1771, and the use of the term dengue by the Queen of Spain in 1801 to describe an acute febrile illness with bone and joint pains, hemorrhage, and jaundice. These texts are evidence of a more generalized use of the term break-bone than previously recognized, and conversely, the specifically Spanish origin of dengue as the name for an illness.

Cognitive Processes that Underlie Mathematical Precociousness in Young Children

ERIC Educational Resources Information Center

Swanson, H. Lee

2006-01-01

The working memory (WM) processes that underlie young children's (ages 6-8 years) mathematical precociousness were examined. A battery of tests that assessed components of WM (phonological loop, visual-spatial sketchpad, and central executive), naming speed, random generation, and fluency was administered to mathematically precocious and…

Synergy between Prkdc and Trp53 regulates stem cell proliferation and GI-ARS after irradiation.

PubMed

Gurley, Kay E; Ashley, Amanda K; Moser, Russell D; Kemp, Christopher J

2017-11-01

Ionizing radiation (IR) is one of the most widely used treatments for cancer. However, acute damage to the gastrointestinal tract or gastrointestinal acute radiation syndrome (GI-ARS) is a major dose-limiting side effect, and the mechanisms that underlie this remain unclear. Here we use mouse models to explore the relative roles of DNA repair, apoptosis, and cell cycle arrest in radiation response. IR induces DNA double strand breaks and DNA-PK mutant Prkdc scid/scid mice are sensitive to GI-ARS due to an inability to repair these breaks. IR also activates the tumor suppressor p53 to trigger apoptotic cell death within intestinal crypt cells and p53 deficient mice are resistant to apoptosis. To determine if DNA-PK and p53 interact to govern radiosensitivity, we compared the response of single and compound mutant mice to 8 Gy IR. Compound mutant Prkdc scid/scid /Trp53 -/- mice died earliest due to severe GI-ARS. While both Prkdc scid/scid and Prkdc scid/scid /Trp53 -/- mutant mice had higher levels of IR-induced DNA damage, particularly within the stem cell compartment of the intestinal crypt, in Prkdc scid/scid /Trp53 -/- mice these damaged cells abnormally progressed through the cell cycle resulting in mitotic cell death. This led to a loss of Paneth cells and a failure to regenerate the differentiated epithelial cells required for intestinal function. IR-induced apoptosis did not correlate with radiosensitivity. Overall, these data reveal that DNA repair, mediated by DNA-PK, and cell cycle arrest, mediated by p53, cooperate to protect the stem cell niche after DNA damage, suggesting combination approaches to modulate both pathways may be beneficial to reduce GI-ARS. As many cancers harbor p53 mutations, this also suggests targeting DNA-PK may be effective to enhance sensitivity of p53 mutant tumors to radiation.

p73 coordinates with Δ133p53 to promote DNA double-strand break repair.

PubMed

Gong, Hongjian; Zhang, Yuxi; Jiang, Kunpeng; Ye, Shengfan; Chen, Shuming; Zhang, Qinghe; Peng, Jinrong; Chen, Jun

2018-03-06

Tumour repressor p53 isoform Δ133p53 is a target gene of p53 and an antagonist of p53-mediated apoptotic activity. We recently demonstrated that Δ133p53 promotes DNA double-strand break (DSB) repair by upregulating transcription of the repair genes RAD51, LIG4 and RAD52 in a p53-independent manner. However, Δ133p53 lacks the transactivation domain of full-length p53, and the mechanism by which it exerts transcriptional activity independently of full-length p53 remains unclear. In this report, we describe the accumulation of high levels of both Δ133p53 and p73 (a p53 family member) at 24 h post γ-irradiation (hpi). Δ133p53 can form a complex with p73 upon γ-irradiation. The co-expression of Δ133p53 and p73, but not either protein alone, can significantly promote DNA DSB repair mechanisms, including homologous recombination (HR), non-homologous end joining (NHEJ) and single-strand annealing (SSA). p73 and Δ133p53 act synergistically to promote the expression of RAD51, LIG4 and RAD52 by joining together to bind to region containing a Δ133p53-responsive element (RE) and a p73-RE in the promoters of all three repair genes. In addition to its accumulation at 24 hpi, p73 protein expression also peaks at 4 hpi. The depletion of p73 not only reduces early-stage apoptotic frequency (4-6 hpi), but also significantly increases later-stage DNA DSB accumulation (48 hpi), leading to cell cycle arrest in the G2 phase and, ultimately, cell senescence. In summary, the apoptotic regulator p73 also coordinates with Δ133p53 to promote DNA DSB repair, and the loss of function of p73 in DNA DSB repair may underlie spontaneous and carcinogen-induced tumorigenesis in p73 knockout mice.

The effects of a mid-task break on the brain connectome in healthy participants: A resting-state functional MRI study.

PubMed

Sun, Yu; Lim, Julian; Dai, Zhongxiang; Wong, KianFoong; Taya, Fumihiko; Chen, Yu; Li, Junhua; Thakor, Nitish; Bezerianos, Anastasios

2017-05-15

Although rest breaks are commonly administered as a countermeasure to reduce mental fatigue and boost cognitive performance, the effects of taking a break on behavior are not consistent. Moreover, our understanding of the underlying neural mechanisms of rest breaks and how they modulate mental fatigue is still rudimentary. In this study, we investigated the effects of receiving a rest break on the topological properties of brain connectivity networks via a two-session experimental paradigm, in which one session comprised four successive blocks of a mentally demanding visual selective attention task (No-rest session), whereas the other contained a rest break between the second and third task blocks (Rest session). Functional brain networks were constructed using resting-state functional MRI data recorded from 20 healthy adults before and after the performance of the task blocks. Behaviorally, subjects displayed robust time-on-task (TOT) declines, as reflected by increasingly slower reaction time as the test progressed and lower post-task self-reported ratings of engagement. However, we did not find a significant effect on task performance due to administering a mid-task break. Compared to pre-task measurements, post-task functional brain networks demonstrated an overall decrease of optimal small-world properties together with lower global efficiency. Specifically, we found TOT-related reduced nodal efficiency in brain regions that mainly resided in the subcortical areas. More interestingly, a significant block-by-session interaction was revealed in local efficiency, attributing to a significant post-task decline in No-rest session and a preserved local efficiency when a mid-task break opportunity was introduced in the Rest session. Taken together, these findings augment our understanding of how the resting brain reorganizes following the accumulation of prolonged task, suggest dissociable processes between the neural mechanisms of fatigue and recovery, and provide some of the first quantitative insights into the cognitive neuroscience of work and rest. Copyright © 2017 Elsevier Inc. All rights reserved.

Developmental changes in genetic and environmental influences on rule-breaking and aggression: age and pubertal development.

PubMed

Harden, K Paige; Patterson, Megan W; Briley, Daniel A; Engelhardt, Laura E; Kretsch, Natalie; Mann, Frank D; Tackett, Jennifer L; Tucker-Drob, Elliot M

2015-12-01

Antisocial behavior (ASB) can be meaningfully divided into nonaggressive rule-breaking versus aggressive dimensions, which differ in developmental course and etiology. Previous research has found that genetic influences on rule-breaking, but not aggression, increase from late childhood to mid-adolescence. This study tested the extent to which the developmental increase in genetic influence on rule-breaking was associated with pubertal development compared to chronological age. Child and adolescent twins (n = 1,031), ranging in age from 8 to 20 years (M age = 13.5 years), were recruited from public schools as part of the Texas Twin Project. Participants reported on their pubertal development using the Pubertal Development Scale and on their involvement in ASB on items from the Child Behavior Checklist. Measurement invariance of ASB subtypes across age groups (≤12 years vs. >12 years old) was tested using confirmatory factor analyses. Quantitative genetic modeling was used to test whether the genetic and environmental influences on aggression and rule-breaking were moderated by age, pubertal status, or both. Quantitative genetic modeling indicated that genetic influences specific to rule-breaking increased as a function of pubertal development controlling for age (a gene × puberty interaction), but did not vary as a function of age controlling for pubertal status. There were no developmental differences in the genetic etiology of aggression. Family-level environmental influences common to aggression and rule-breaking decreased with age, further contributing to the differentiation between these subtypes of ASB from childhood to adolescence. Future research should discriminate between alternative possible mechanisms underlying gene × puberty interactions on rule-breaking forms of antisocial behavior, including possible effects of pubertal hormones on gene expression. © 2015 Association for Child and Adolescent Mental Health.

Genetic neuroscience of mammalian learning and memory.

PubMed Central

Tonegawa, Susumu; Nakazawa, Kazu; Wilson, Matthew A

2003-01-01

Our primary research interest is to understand the molecular and cellular mechanisms on neuronal circuitry underlying the acquisition, consolidation and retrieval of hippocampus-dependent memory in rodents. We study these problems by producing genetically engineered (i.e. spatially targeted and/or temporally restricted) mice and analysing these mice by multifaceted methods including molecular and cellular biology, in vitro and in vivo physiology and behavioural studies. We attempt to identify deficits at each of the multiple levels of complexity in specific brain areas or cell types and deduce those deficits that underlie specific learning or memory. We will review our recent studies on the acquisition, consolidation and recall of memories that have been conducted with mouse strains in which genetic manipulations were targeted to specific types of cells in the hippocampus or forebrain of young adult mice. PMID:12740125

Cellular and Molecular Underpinnings of Neuronal Assembly in the Central Auditory System during Mouse Development

PubMed Central

Di Bonito, Maria; Studer, Michèle

2017-01-01

During development, the organization of the auditory system into distinct functional subcircuits depends on the spatially and temporally ordered sequence of neuronal specification, differentiation, migration and connectivity. Regional patterning along the antero-posterior axis and neuronal subtype specification along the dorso-ventral axis intersect to determine proper neuronal fate and assembly of rhombomere-specific auditory subcircuits. By taking advantage of the increasing number of transgenic mouse lines, recent studies have expanded the knowledge of developmental mechanisms involved in the formation and refinement of the auditory system. Here, we summarize several findings dealing with the molecular and cellular mechanisms that underlie the assembly of central auditory subcircuits during mouse development, focusing primarily on the rhombomeric and dorso-ventral origin of auditory nuclei and their associated molecular genetic pathways. PMID:28469562

A construct divided: prosocial behavior as helping, sharing, and comforting subtypes.

PubMed

Dunfield, Kristen A

2014-01-01

The development and maintenance of prosocial, other-oriented behaviors has been of considerable recent interest. Though it is clear that prosocial behaviors emerge early and play a uniquely important role in the social lives of humans, there is less consensus regarding the mechanisms that underlie and maintain these fundamental acts. The goal of this paper is to clarify inconsistencies in our understanding of the early emergence and development of prosocial behavior by proposing a taxonomy of prosocial behavior anchored in the social-cognitive constraints that underlie the ability to act on behalf of others. I will argue that within the general domain of prosocial behavior, other-oriented actions can be categorized into three distinct types (helping, sharing, and comforting) that reflect responses to three distinct negative states (instrumental need, unmet material desire, and emotional distress). In support of this proposal, I will demonstrate that the three varieties of prosocial behavior show unique ages of onset, uncorrelated patterns of production, and distinct patterns of individual differences. Importantly, by differentiating specific varieties of prosocial behavior within the general category, we can begin to explain inconsistencies in the past literature and provide a framework for directing future research into the ontogenetic origins of these essential social behaviors.

Understanding the Cognitive and Genetic Underpinnings of Procrastination: Evidence for Shared Genetic Influences with Goal Management and Executive Function Abilities

PubMed Central

Gustavson, Daniel E.; Miyake, Akira; Hewitt, John K.; Friedman, Naomi P.

2015-01-01

Previous research has suggested that individual differences in procrastination are tied to everyday goal-management abilities, but little research has been conducted on specific cognitive abilities that may underlie tendencies for procrastination, such as executive functions (EFs). In this study, we used behavioral genetics methodology to investigate two hypotheses about the relationships between procrastination and EF ability: (a) that procrastination is negatively correlated with general EF ability, and (b) that this relationship is due to the genetic components of procrastination that are most related to other everyday goal-management abilities. The results confirmed both of these hypotheses. Procrastination was related to worse general EF ability at both the phenotypic and genetic levels, and this relationship was due to the component of procrastination shared with self-report measures of everyday goal-management failures. These results were observed even after controlling for potential self-report biases stemming from the urge to respond in a socially desirable manner. Together, these findings provide strong evidence for growing theories of procrastination emphasizing the importance of goal-related cognitive abilities and further highlight important genetic influences that underlie procrastination. PMID:26389573

Understanding the cognitive and genetic underpinnings of procrastination: Evidence for shared genetic influences with goal management and executive function abilities.

PubMed

Gustavson, Daniel E; Miyake, Akira; Hewitt, John K; Friedman, Naomi P

2015-12-01

Previous research has suggested that individual differences in procrastination are tied to everyday goal-management abilities, but little research has been conducted on specific cognitive abilities that may underlie tendencies for procrastination, such as executive functions (EFs). In this study, we used behavioral genetics methodology to investigate 2 hypotheses about the relationships between procrastination and EF ability: (a) that procrastination is negatively correlated with general EF ability, and (b) that this relationship is due to the genetic components of procrastination that are most related to other everyday goal-management abilities. The results confirmed both of these hypotheses. Procrastination was related to worse general EF ability at both the phenotypic and genetic levels, and this relationship was due to the component of procrastination shared with self-report measures of everyday goal-management failures. These results were observed even after controlling for potential self-report biases stemming from the urge to respond in a socially desirable manner. Together, these findings provide strong evidence for growing theories of procrastination emphasizing the importance of goal-related cognitive abilities and further highlight important genetic influences that underlie procrastination. (c) 2015 APA, all rights reserved).

Structure Building Predicts Grades in College Psychology and Biology

ERIC Educational Resources Information Center

Arnold, Kathleen M.; Daniel, David B.; Jensen, Jamie L.; McDaniel, Mark A.; Marsh, Elizabeth J.

2016-01-01

Knowing what skills underlie college success can allow students, teachers, and universities to identify and to help at-risk students. One skill that may underlie success across a variety of subject areas is structure building, the ability to create mental representations of narratives (Gernsbacher, Varner, & Faust, 1990). We tested if…

Recognising Value Tensions That Underlie Problems in Inclusive Education

ERIC Educational Resources Information Center

Norwich, Brahm

2014-01-01

This paper aims to examine some tensions that underlie inclusive education as regards pupils with disabilities and difficulties. Two key tensions are analysed: difference as enabling-stigmatising (dilemmas of difference) and participation-protection, both of which can lead to significant dilemmas. Berlin's hedgehog-fox distinction about the unity…

Addition of DNA to CrVI and Cytochrome b5 Containing Proteoliposomes Leads to Generation of DNA Strand Breaks and CrIII Complexes

PubMed Central

Borthiry, Griselda R.; Antholine, William E.; Myers, Judith M.; Myers, Charles R.

2009-01-01

Chromium (Cr) is a cytotoxic metal that can be associated with a variety of types of DNA damage, including Cr-DNA adducts and strand breaks. Prior studies with purified human cytochrome b5 and NADPH :P450 reductase in reconstituted proteoliposomes (PLs) demonstrated rapid reduction of CrVI (hexavalent chromium, as CrO42− ), and the generation of CrV, superoxide (O2·−) , and hydroxyl radical (HO˙). Studies reported here examined the potential for the species produced by this system to interact with DNA. Strand breaks of purified plasmid DNA increased over time aerobically, but were not observed in the absence of O2. CrV is formed under both conditions, so the breaks are not mediated directly by CrV. The aerobic strand breaks were significantly prevented by catalase and EtOH, but not by the metal chelator diethylenetriaminepentaacetic acid (DTPA), suggesting that they are largely due to HO˙ from Cr-mediated redox cycling. EPR was used to assess the formation of Cr-DNA complexes. Following a 10-min incubation of PLs, CrO42− , and plasmid DNA, intense EPR signals at g = 5.7and g = 5.0 were observed. These signals are attributed to specific CrIII complexes with large zero field splitting (ZFS). Without DNA, the signals in the g = 5 region were weak. The large ZFS signals were not seen, when CrIIICl3 was incubated with DNA, suggesting that the CrIII–DNA interactions are different when generated by the PLs. After 24 h, a broad signal at g = 2 is attributed to CrIII complexes with a small ZFS. This g = 2 signal was observed without DNA, but it was different from that seen with plasmid. It is concluded that EPR can detect specific CrIII complexes that depend on the presence of plasmid DNA and the manner in which the CrIII is formed. PMID:18729091

New methods for the analysis of the protein-solvent interface

NASA Astrophysics Data System (ADS)

Goodfellow, Julia M.; Pitt, William R.; Smart, Oliver S.; Williams, Mark A.

1995-09-01

The protein-solvent interface is complex and may include solvent channels and cavities as well as the normal surface water molecules. We describe several algorithms for investigating the intra- and inter-molecular interactions of proteins in general but with the aim of developing methods to accurately and definitively characterise the interactions of water and other small ligands with proteins. Specifically, we present the methods which underlie three programs (AQUARIUS2, HOLE and PRO_ACT) which can be used to to look at different aspects of these interactions.

Neural circuitry engaged by prostaglandins during the sickness syndrome.

PubMed

Saper, Clifford B; Romanovsky, Andrej A; Scammell, Thomas E

2012-07-26

During illnesses caused by infectious disease or other sources of inflammation, a suite of brain-mediated responses called the sickness syndrome occurs, which includes fever, anorexia, sleepiness, hyperalgesia and elevated corticosteroid secretion. Much of the sickness syndrome is mediated by prostaglandins acting on the brain and can be prevented by nonsteroidal anti-inflammatory drugs, such as aspirin or ibuprofen, that block prostaglandin synthesis. By examining which prostaglandins are produced at which sites and how they interact with the nervous system, researchers have identified specific neural circuits that underlie the sickness syndrome.

Neural Circuitry Engaged by Prostaglandins during the Sickness Syndrome

PubMed Central

Saper, Clifford B.; Romanovsky, Andrej A.; Scammell, Thomas E.

2013-01-01

During illnesses caused by infectious disease or other sources of inflammation, a suite of brain-mediated responses called the “sickness syndrome” occurs, including fever, anorexia, sleepiness, hyperalgesia, and elevated corticosteroid secretion. Much of the sickness syndrome is mediated by prostaglandins acting on the brain, and can be prevented by non-steroidal anti-inflammatory drugs, such as aspirin or ibuprofen, that block prostaglandin synthesis. By examining which prostaglandins are produced at which sites and how they interact with the nervous system, researchers have identified specific neural circuits that underlie the sickness syndrome. PMID:22837039

Bili lights

MedlinePlus

Phototherapy for jaundice; Bilirubin - bili lights; Neonatal care - bili lights; Newborn care - bili lights ... Phototherapy involves shining fluorescent light from the bili lights on bare skin. A specific wavelength of light can break down bilirubin into a form that ...

Layer-specific morphological and molecular differences in neocortical astrocytes and their dependence on neuronal layers.

PubMed

Lanjakornsiripan, Darin; Pior, Baek-Jun; Kawaguchi, Daichi; Furutachi, Shohei; Tahara, Tomoaki; Katsuyama, Yu; Suzuki, Yutaka; Fukazawa, Yugo; Gotoh, Yukiko

2018-04-24

Non-pial neocortical astrocytes have historically been thought to comprise largely a nondiverse population of protoplasmic astrocytes. Here we show that astrocytes of the mouse somatosensory cortex manifest layer-specific morphological and molecular differences. Two- and three-dimensional observations revealed that astrocytes in the different layers possess distinct morphologies as reflected by differences in cell orientation, territorial volume, and arborization. The extent of ensheathment of synaptic clefts by astrocytes in layer II/III was greater than that by those in layer VI. Moreover, differences in gene expression were observed between upper-layer and deep-layer astrocytes. Importantly, layer-specific differences in astrocyte properties were abrogated in reeler and Dab1 conditional knockout mice, in which neuronal layers are disturbed, suggesting that neuronal layers are a prerequisite for the observed morphological and molecular differences of neocortical astrocytes. This study thus demonstrates the existence of layer-specific interactions between neurons and astrocytes, which may underlie their layer-specific functions.

Cnidarian Cell Type Diversity and Regulation Revealed by Whole-Organism Single-Cell RNA-Seq.

PubMed

Sebé-Pedrós, Arnau; Saudemont, Baptiste; Chomsky, Elad; Plessier, Flora; Mailhé, Marie-Pierre; Renno, Justine; Loe-Mie, Yann; Lifshitz, Aviezer; Mukamel, Zohar; Schmutz, Sandrine; Novault, Sophie; Steinmetz, Patrick R H; Spitz, François; Tanay, Amos; Marlow, Heather

2018-05-31

The emergence and diversification of cell types is a leading factor in animal evolution. So far, systematic characterization of the gene regulatory programs associated with cell type specificity was limited to few cell types and few species. Here, we perform whole-organism single-cell transcriptomics to map adult and larval cell types in the cnidarian Nematostella vectensis, a non-bilaterian animal with complex tissue-level body-plan organization. We uncover eight broad cell classes in Nematostella, including neurons, cnidocytes, and digestive cells. Each class comprises different subtypes defined by the expression of multiple specific markers. In particular, we characterize a surprisingly diverse repertoire of neurons, which comparative analysis suggests are the result of lineage-specific diversification. By integrating transcription factor expression, chromatin profiling, and sequence motif analysis, we identify the regulatory codes that underlie Nematostella cell-specific expression. Our study reveals cnidarian cell type complexity and provides insights into the evolution of animal cell-specific genomic regulation. Copyright © 2018 Elsevier Inc. All rights reserved.

Improving Executive Function and its Neurobiological Mechanisms through a Mindfulness-Based Intervention: Advances within the Field of Developmental Neuroscience.

PubMed

Tang, Yi-Yuan; Yang, Lizhu; Leve, Leslie D; Harold, Gordon T

2012-12-01

Poor executive function (EF) has been associated with a host of short- and long-term problems across the lifespan, including elevated rates of attention deficit hyperactivity disorder, depression, drug abuse, and antisocial behavior. Mindfulness-based interventions that focus on increasing awareness of one's thoughts, emotions, and actions have been shown to improve specific aspects of EF, including attention, cognitive control, and emotion regulation. In this article, we apply a developmental neuroscience perspective to review research relevant to one specific mindfulness-based intervention, Integrative Body-Mind Training (IBMT). Randomized controlled trials of IBMT indicate improvements in specific EF components, and uniquely highlight the role of neural circuitry specific to the anterior cingulate cortex (ACC) and the autonomic nervous system (ANS) as two brain-based mechanisms that underlie IBMT-related improvements. The relevance of improving specific dimensions of EF through short-term IBMT to prevent a cascade of risk behaviors for children and adolescents is described and future research directions are proposed.

Hydrogen cyanamide breaks grapevine bud dormancy in the summer through transient activation of gene expression and accumulation of reactive oxygen and nitrogen species.

PubMed

Sudawan, Boonyawat; Chang, Chih-Sheng; Chao, Hsiu-Fung; Ku, Maurice S B; Yen, Yung-Fu

2016-09-15

Hydrogen cyanamide (HC) and pruning (P) have frequently been used to break dormancy in grapevine floral buds. However, the exact underlying mechanism remains elusive. This study aimed to address the early mode of action of these treatments on accumulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and expression of related genes in the dormancy breaking buds of grapevine in the summer. The budbreak rates induced by pruning (P), hydrogen cyanamide (HC), pruning plus hydrogen cyanamide (PHC) and water (control) after 8 days were 33, 53, 95, and 0 %, respectively. Clearly, HC was more effective in stimulating grapevine budbreak and P further enhanced its potency. In situ staining of longitudinal bud sections after 12 h of treatments detected high levels of ROS and nitric oxide (NO) accumulated in the buds treated with PHC, compared with HC or P alone. The amounts of ROS and NO accumulated were highly correlated with the rates of budbreak among these treatments, highlighting the importance of a rapid, transient accumulation of sublethal levels of ROS and RNS in dormancy breaking. Microarray analysis revealed specific alterations in gene expression in dormancy breaking buds induced by P, HC and PHC after 24 h of treatment. Relative to control, PHC altered the expression of the largest number of genes, while P affected the expression of the least number of genes. PHC also exerted a greater intensity in transcriptional activation of these genes. Gene ontology (GO) analysis suggests that alteration in expression of ROS related genes is the major factor responsible for budbreak. qRT-PCR analysis revealed the transient expression dynamics of 12 specific genes related to ROS generation and scavenge during the 48 h treatment with PHC. Our results suggest that rapid accumulation of ROS and NO at early stage is important for dormancy release in grapevine in the summer, and the identification of the commonly expressed specific genes among the treatments allowed the construction of the signal transduction pathway related to ROS/RNS metabolism during dormancy release. The rapid accumulation of a sublethal level of ROS/RNS subsequently induces cell wall loosening and expansion for bud sprouting.

Childhood Tuberculosis and Malnutrition

PubMed Central

Jaganath, Devan; Mupere, Ezekiel

2012-01-01

Despite the burden of both malnutrition and tuberculosis in children worldwide, there are few studies on the mechanisms that underlie this relationship. From available research, it appears that malnutrition is a predictor of tuberculosis disease and is associated with worse outcomes. This is supported through several lines of evidence, including the role of vitamin D receptor genotypes, malnutrition's effects on immune development, respiratory infections among malnourished children, and limited work specifically on pediatric tuberculosis and malnutrition. Nutritional supplementation has yet to suggest significant benefits on the course of tuberculosis in children. There is a critical need for research on childhood tuberculosis, specifically on how nutritional status affects the risk and progression of tuberculosis and whether nutritional supplementation improves clinical outcomes or prevents disease. PMID:23033147

The Effect of Break Edge Configuration on the Aerodynamics of Anti-Ice Jet Flow

NASA Astrophysics Data System (ADS)

Tatar, V.; Yildizay, H.; Aras, H.

2015-05-01

One of the components of a turboprop gas turbine engine is the Front Bearing Structure (FBS) which leads air into the compressor. FBS directly encounters with ambient air, as a consequence ice accretion may occur on its static vanes. There are several aerodynamic parameters which should be considered in the design of anti-icing system of FBS, such as diameter, position, exit angle of discharge holes, etc. This research focuses on the effects of break edge configuration over anti-ice jet flow. Break edge operation is a process which is applied to the hole in order to avoid sharp edges which cause high stress concentration. Numerical analyses and flow visualization test have been conducted. Four different break edge configurations were used for this investigation; without break edge, 0.35xD, 74xD, 0.87xD. Three mainstream flow conditions at the inlet of the channel are defined; 10m/s, 20 m/s and 40 m/s. Shear stresses are extracted from numerical analyses near the trailing edge of pressure surface where ice may occur under icing conditions. A specific flow visualization method was used for the experimental study. Vane surface near the trailing edge was dyed and thinner was injected into anti-ice jet flow in order to remove dye from the vane surface. Hence, film effect on the surface could be computed for each testing condition. Thickness of the dye removal area of each case was examined. The results show noticeable effects of break edge operation on jet flow, and the air film effectiveness decreases when mainstream inlet velocity decreases.

Calculation on spectrum of direct DNA damage induced by low-energy electrons including dissociative electron attachment.

PubMed

Liu, Wei; Tan, Zhenyu; Zhang, Liming; Champion, Christophe

2017-03-01

In this work, direct DNA damage induced by low-energy electrons (sub-keV) is simulated using a Monte Carlo method. The characteristics of the present simulation are to consider the new mechanism of DNA damage due to dissociative electron attachment (DEA) and to allow determining damage to specific bases (i.e., adenine, thymine, guanine, or cytosine). The electron track structure in liquid water is generated, based on the dielectric response model for describing electron inelastic scattering and on a free-parameter theoretical model and the NIST database for calculating electron elastic scattering. Ionization cross sections of DNA bases are used to generate base radicals, and available DEA cross sections of DNA components are applied for determining DNA-strand breaks and base damage induced by sub-ionization electrons. The electron elastic scattering from DNA components is simulated using cross sections from different theoretical calculations. The resulting yields of various strand breaks and base damage in cellular environment are given. Especially, the contributions of sub-ionization electrons to various strand breaks and base damage are quantitatively presented, and the correlation between complex clustered DNA damage and the corresponding damaged bases is explored. This work shows that the contribution of sub-ionization electrons to strand breaks is substantial, up to about 40-70%, and this contribution is mainly focused on single-strand break. In addition, the base damage induced by sub-ionization electrons contributes to about 20-40% of the total base damage, and there is an evident correlation between single-strand break and damaged base pair A-T.

A numerical investigation of wave-breaking-induced turbulent coherent structure under a solitary wave

NASA Astrophysics Data System (ADS)

Zhou, Zheyu; Sangermano, Jacob; Hsu, Tian-Jian; Ting, Francis C. K.

2014-10-01

To better understand the effect of wave-breaking-induced turbulence on the bed, we report a 3-D large-eddy simulation (LES) study of a breaking solitary wave in spilling condition. Using a turbulence-resolving approach, we study the generation and the fate of wave-breaking-induced turbulent coherent structures, commonly known as obliquely descending eddies (ODEs). Specifically, we focus on how these eddies may impinge onto bed. The numerical model is implemented using an open-source CFD library of solvers, called OpenFOAM, where the incompressible 3-D filtered Navier-Stokes equations for the water and the air phases are solved with a finite volume scheme. The evolution of the water-air interfaces is approximated with a volume of fluid method. Using the dynamic Smagorinsky closure, the numerical model has been validated with wave flume experiments of solitary wave breaking over a 1/50 sloping beach. Simulation results show that during the initial overturning of the breaking wave, 2-D horizontal rollers are generated, accelerated, and further evolve into a couple of 3-D hairpin vortices. Some of these vortices are sufficiently intense to impinge onto the bed. These hairpin vortices possess counter-rotating and downburst features, which are key characteristics of ODEs observed by earlier laboratory studies using Particle Image Velocimetry. Model results also suggest that those ODEs that impinge onto bed can induce strong near-bed turbulence and bottom stress. The intensity and locations of these near-bed turbulent events could not be parameterized by near-surface (or depth integrated) turbulence unless in very shallow depth.

Deep photometry of two accreted families of globular clusters in the remote M31 halo

NASA Astrophysics Data System (ADS)

Mackey, Dougal

2013-10-01

Globular clusters {GCs} are fossil relics from which we can obtain critical insights into the merger and accretion events that underlie hierarchical galaxy assembly. As part of the major Pan-Andromeda Archaeological Survey {PAndAS} we have discovered two groups of GCs that closely trace narrow stellar debris streams in the M31 halo. These clearly represent two distinct accreted families of GCs - the only known examples apart from the few Galactic GCs arriving with the Sagittarius dwarf. We propose to obtain deep ACS imaging of 14 GCs spanning these two accreted families, allowing us to measure the constituent stellar populations, line-of-sight distance, and structural parameters of each object. We will, for the first time, quantify the typical properties of accreted GCs in the M31 halo as well as the degree of variation amongst them, and how closely they correspond to the suspected accreted GC population in the Milky Way. Combined with new radial velocity measurements for the GCs, our proposed observations will allow us to trace the 3D orbits of the two streams within the M31 halo, and thus break the main degeneracies that plague numerical models designed to probe the gravitational potential and distribution of dark mass.

Constructing local integrals of motion in the many-body localized phase

NASA Astrophysics Data System (ADS)

Chandran, Anushya; Kim, Isaac H.; Vidal, Guifre; Abanin, Dmitry A.

2015-02-01

Many-body localization provides a generic mechanism of ergodicity breaking in quantum systems. In contrast to conventional ergodic systems, many-body-localized (MBL) systems are characterized by extensively many local integrals of motion (LIOM), which underlie the absence of transport and thermalization in these systems. Here we report a physically motivated construction of local integrals of motion in the MBL phase. We show that any local operator (e.g., a local particle number or a spin-flip operator), evolved with the system's Hamiltonian and averaged over time, becomes a LIOM in the MBL phase. Such operators have a clear physical meaning, describing the response of the MBL system to a local perturbation. In particular, when a local operator represents a density of some globally conserved quantity, the corresponding LIOM describes how this conserved quantity propagates through the MBL phase. Being uniquely defined and experimentally measurable, these LIOMs provide a natural tool for characterizing the properties of the MBL phase, in both experiments and numerical simulations. We demonstrate the latter by numerically constructing an extensive set of LIOMs in the MBL phase of a disordered spin-chain model. We show that the resulting LIOMs are quasilocal and use their decay to extract the localization length and establish the location of the transition between the MBL and ergodic phases.

Machine Learning-based Transient Brokers for Real-time Classification of the LSST Alert Stream

NASA Astrophysics Data System (ADS)

Narayan, Gautham; Zaidi, Tayeb; Soraisam, Monika; ANTARES Collaboration

2018-01-01

The number of transient events discovered by wide-field time-domain surveys already far outstrips the combined followup resources of the astronomical community. This number will only increase as we progress towards the commissioning of the Large Synoptic Survey Telescope (LSST), breaking the community's current followup paradigm. Transient brokers - software to sift through, characterize, annotate and prioritize events for followup - will be a critical tool for managing alert streams in the LSST era. Developing the algorithms that underlie the brokers, and obtaining simulated LSST-like datasets prior to LSST commissioning, to train and test these algorithms are formidable, though not insurmountable challenges. The Arizona-NOAO Temporal Analysis and Response to Events System (ANTARES) is a joint project of the National Optical Astronomy Observatory and the Department of Computer Science at the University of Arizona. We have been developing completely automated methods to characterize and classify variable and transient events from their multiband optical photometry. We describe the hierarchical ensemble machine learning algorithm we are developing, and test its performance on sparse, unevenly sampled, heteroskedastic data from various existing observational campaigns, as well as our progress towards incorporating these into a real-time event broker working on live alert streams from time-domain surveys.

Opsin co-expression in Limulus photoreceptors: differential regulation by light and a circadian clock

PubMed Central

Katti, C.; Kempler, K.; Porter, M. L.; Legg, A.; Gonzalez, R.; Garcia-Rivera, E.; Dugger, D.; Battelle, B.-A.

2010-01-01

A long-standing concept in vision science has held that a single photoreceptor expresses a single type of opsin, the protein component of visual pigment. However, the number of examples in the literature of photoreceptors from vertebrates and invertebrates that break this rule is increasing. Here, we describe a newly discovered Limulus opsin, Limulus opsin5, which is significantly different from previously characterized Limulus opsins, opsins1 and 2. We show that opsin5 is co-expressed with opsins1 and 2 in Limulus lateral and ventral eye photoreceptors and provide the first evidence that the expression of co-expressed opsins can be differentially regulated. We show that the relative levels of opsin5 and opsin1 and 2 in the rhabdom change with a diurnal rhythm and that their relative levels are also influenced by the animal's central circadian clock. An analysis of the sequence of opsin5 suggests it is sensitive to visible light (400–700 nm) but that its spectral properties may be different from that of opsins1 and 2. Changes in the relative levels of these opsins may underlie some of the dramatic day–night changes in Limulus photoreceptor function and may produce a diurnal change in their spectral sensitivity. PMID:20639420

Sound Morality: Irritating and Icky Noises Amplify Judgments in Divergent Moral Domains

ERIC Educational Resources Information Center

Seidel, Angelika; Prinz, Jesse

2013-01-01

Theoretical models and correlational research suggest that anger and disgust play different roles in moral judgment. Anger is theorized to underlie reactions to crimes against persons, such as battery and unfairness, and disgust is theorized to underlie reactions to crimes against nature, such as sexual transgressions and cannibalism. To date,…

Are ADHD Symptoms Associated with Delay Aversion or Choice Impulsivity? A General Population Study

ERIC Educational Resources Information Center

Paloyelis, Yannis; Asherson, Philip; Kuntsi, Jonna

2009-01-01

The relationship of attention-deficit/hyperactivity disorder (ADHD) with choice impulsivity is examined. Findings were found to indicate that primary constitutional processes that underlie choice impulsivity and their potential role in behavioral inattention are important. It was also found that behavioral and brain processes that underlie choice…

Alkaline Comet Assay for Assessing DNA Damage in Individual Cells.

PubMed

Pu, Xinzhu; Wang, Zemin; Klaunig, James E

2015-08-06

Single-cell gel electrophoresis, commonly called a comet assay, is a simple and sensitive method for assessing DNA damage at the single-cell level. It is an important technique in genetic toxicological studies. The comet assay performed under alkaline conditions (pH >13) is considered the optimal version for identifying agents with genotoxic activity. The alkaline comet assay is capable of detecting DNA double-strand breaks, single-strand breaks, alkali-labile sites, DNA-DNA/DNA-protein cross-linking, and incomplete excision repair sites. The inclusion of digestion of lesion-specific DNA repair enzymes in the procedure allows the detection of various DNA base alterations, such as oxidative base damage. This unit describes alkaline comet assay procedures for assessing DNA strand breaks and oxidative base alterations. These methods can be applied in a variety of cells from in vitro and in vivo experiments, as well as human studies. Copyright © 2015 John Wiley & Sons, Inc.

Noncritical generation of nonclassical frequency combs via spontaneous rotational symmetry breaking

NASA Astrophysics Data System (ADS)

Navarrete-Benlloch, Carlos; Patera, Giuseppe; de Valcárcel, Germán J.

2017-10-01

Synchronously pumped optical parametric oscillators (SPOPOs) are optical cavities driven by mode-locked lasers, and containing a nonlinear crystal capable of down-converting a frequency comb to lower frequencies. SPOPOs have received a lot of attention lately because their intrinsic multimode nature makes them compact sources of quantum correlated light with promising applications in modern quantum information technologies. In this work we show that SPOPOs are also capable of accessing the challenging and interesting regime where spontaneous symmetry breaking confers strong nonclassical properties to the emitted light, which has eluded experimental observation so far. Apart from opening the possibility of studying experimentally this elusive regime of dissipative phase transitions, our predictions will have a practical impact, since we show that spontaneous symmetry breaking provides a specific spatiotemporal mode with large quadrature squeezing for any value of the system parameters, turning SPOPOs into robust sources of highly nonclassical light above threshold.

The Potential for Helicopter Passenger Service in Major Urban Areas. [cost analysis

NASA Technical Reports Server (NTRS)

Dajani, J. S.; Stortstrom, R. G.; Warner, D. B.

1977-01-01

An interurban helicopter cost model having the capability of selecting an efficient helicopter network for a given city in terms of service and total operating costs was developed. This model which is based upon the relationship between total and direct operating costs and the number of block hours of helicopter operation is compiled in terms of a computer program which simulates the operation of an intracity helicopter fleet over a given network. When applied to specific urban areas, the model produces results in terms of a break-even air passenger market penetration rate, which is the percent of the air travelers in each of those areas that must patronize the helicopter network to make it break even commercially. A total of twenty major metropolitan areas are analyzed and are ranked initially according to cost per seat mile and then according to break-even penetration rate.

Biological Clues to Potent DNA-Damaging Activities in Food and Flavoring

PubMed Central

Hossain, M. Zulfiquer; Gilbert, Samuel F.; Patel, Kalpesh; Ghosh, Soma; Bhunia, Anil K.; Kern, Scott E.

2013-01-01

Population differences in age-related diseases and cancer could stem from differences in diet. To characterize DNA strand-breaking activities in selected foods/beverages, flavorings, and some of their constituent chemicals, we used p53R cells, a cellular assay sensitive to such breaks. Substances testing positive included reference chemicals: quinacrine (peak response, 51X) and etoposide (33X); flavonoids: EGCG (19X), curcumin (12X), apigenin (9X), and quercetin (7X); beverages: chamomile (11X), green (21X), and black tea (26X) and coffee (3 to 29X); and liquid smoke (4 to 28X). Damage occurred at dietary concentrations: etoposide near 5 μg/ml produced responses similar to a 1:1000 dilution of liquid smoke, a 1:20 dilution of coffee, and a 1:5 dilution of tea. Pyrogallol-related chemicals and tannins are present in dietary sources and individually produced strong activity: pyrogallol (30X), 3-methoxycatechol (25X), gallic acid (21X), and 1,2,4-benzenetriol (21X). From structure-activity relationships, high activities depended on specific orientations of hydroxyls on the benzene ring. Responses accompanied cellular signals characteristic of DNA breaks such as H2AX phosphorylation. Breaks were also directly detected by comet assay. Cellular toxicological effects of foods and flavorings could guide epidemiologic and experimental studies of potential disease risks from DNA strand-breaking chemicals in diets. PMID:23402862

Attributing Historical Changes in Probabilities of Record-Breaking Daily Temperature and Precipitation Extreme Events

DOE PAGES

Shiogama, Hideo; Imada, Yukiko; Mori, Masato; ...

2016-08-07

Here, we describe two unprecedented large (100-member), longterm (61-year) ensembles based on MRI-AGCM3.2, which were driven by historical and non-warming climate forcing. These ensembles comprise the "Database for Policy Decision making for Future climate change (d4PDF)". We compare these ensembles to large ensembles based on another climate model, as well as to observed data, to investigate the influence of anthropogenic activities on historical changes in the numbers of record-breaking events, including: the annual coldest daily minimum temperature (TNn), the annual warmest daily maximum temperature (TXx) and the annual most intense daily precipitation event (Rx1day). These two climate model ensembles indicatemore » that human activity has already had statistically significant impacts on the number of record-breaking extreme events worldwide mainly in the Northern Hemisphere land. Specifically, human activities have altered the likelihood that a wider area globally would suffer record-breaking TNn, TXx and Rx1day events than that observed over the 2001- 2010 period by a factor of at least 0.6, 5.4 and 1.3, respectively. However, we also find that the estimated spatial patterns and amplitudes of anthropogenic impacts on the probabilities of record-breaking events are sensitive to the climate model and/or natural-world boundary conditions used in the attribution studies.« less

(Oncogenic action of ionizing radiation)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1990-01-01

An extensive experiment involving approximately 400 rats exposed to the neon ion beam at the Bevalac in Berkeley, CA and to electrons is nearing completion. The carcinogenicity of energetic electrons was determined for comparison with the neon ion results. As in past reports we will describe progress in three areas corresponding to the specific aims of the proposal: (1) carcinogenesis and DNA strand breaks in rat skin following exposure by the neon ions or electrons; (2) DNA strand breaks in the epidermis as a function of radiation penetration; (3) oncogene activation in radiation-induced rat skin cancers. 72 refs., 6 tabs.

Deciphering the Code of the Cancer Genome: Mechanisms of Chromosome Rearrangement

PubMed Central

Willis, Nicholas A.; Rass, Emilie; Scully, Ralph

2015-01-01

Chromosome rearrangement plays a causal role in tumorigenesis by contributing to the inactivation of tumor suppressor genes, the dysregulated expression or amplification of oncogenes and the generation of novel gene fusions. Chromosome breaks are important intermediates in this process. How, when and where these breaks arise and the specific mechanisms engaged in their repair strongly influence the resulting patterns of chromosome rearrangement. Here, we review recent progress in understanding how certain distinctive features of the cancer genome, including clustered mutagenesis, tandem segmental duplications, complex breakpoints, chromothripsis, chromoplexy and chromoanasynthesis may arise. PMID:26726318

Activation induced deaminase C-terminal domain links DNA breaks to end protection and repair during class switch recombination

PubMed Central

Zahn, Astrid; Eranki, Anil K.; Patenaude, Anne-Marie; Methot, Stephen P.; Fifield, Heather; Cortizas, Elena M.; Foster, Paul; Imai, Kohsuke; Durandy, Anne; Larijani, Mani; Verdun, Ramiro E.; Di Noia, Javier M.

2014-01-01

Activation-induced deaminase (AID) triggers antibody class switch recombination (CSR) in B cells by initiating DNA double strand breaks that are repaired by nonhomologous end-joining pathways. A role for AID at the repair step is unclear. We show that specific inactivation of the C-terminal AID domain encoded by exon 5 (E5) allows very efficient deamination of the AID target regions but greatly impacts the efficiency and quality of subsequent DNA repair. Specifically eliminating E5 not only precludes CSR but also, causes an atypical, enzymatic activity-dependent dominant-negative effect on CSR. Moreover, the E5 domain is required for the formation of AID-dependent Igh-cMyc chromosomal translocations. DNA breaks at the Igh switch regions induced by AID lacking E5 display defective end joining, failing to recruit DNA damage response factors and undergoing extensive end resection. These defects lead to nonproductive resolutions, such as rearrangements and homologous recombination that can antagonize CSR. Our results can explain the autosomal dominant inheritance of AID variants with truncated E5 in patients with hyper-IgM syndrome 2 and establish that AID, through the E5 domain, provides a link between DNA damage and repair during CSR. PMID:24591601

Chromosome neighborhood composition determines translocation outcomes after exposure to high-dose radiation in primary cells.

PubMed

Brianna Caddle, Lura; Grant, Jeremy L; Szatkiewicz, Jin; van Hase, Johann; Shirley, Bobbi-Jo; Bewersdorf, Joerg; Cremer, Christoph; Arneodo, Alain; Khalil, Andre; Mills, Kevin D

2007-01-01

Radiation exposure is an occupational hazard for military personnel, some health care professionals, airport security screeners, and medical patients, with some individuals at risk for acute, high-dose exposures. Therefore, the biological effects of radiation, especially the potential for chromosome damage, are major occupational and health concerns. However, the biophysical mechanisms of chromosome instability subsequent to radiation-induced DNA damage are poorly understood. It is clear that interphase chromosomes occupy discrete structural and functional subnuclear domains, termed chromosome territories (CT), which may be organized into 'neighborhoods' comprising groups of specific CTs. We directly evaluated the relationship between chromosome positioning, neighborhood composition, and translocation partner choice in primary lymphocytes, using a cell-based system in which we could induce multiple, concentrated DNA breaks via high-dose irradiation. We critically evaluated mis-rejoining profiles and tested whether breaks occurring nearby were more likely to fuse than breaks occurring at a distance. We show that CT neighborhoods comprise heterologous chromosomes, within which inter-CT distances directly relate to translocation partner choice. These findings demonstrate that interphase chromosome arrangement is a principal factor in genomic instability outcomes in primary lymphocytes, providing a structural context for understanding the biological effects of radiation exposure, and the molecular etiology of tumor-specific translocation patterns.

Fear Extinction Memory Consolidation Requires Potentiation of Pontine-Wave Activity during REM Sleep

PubMed Central

Datta, Subimal; O'Malley, Matthew W .

2013-01-01

Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction. PMID:23467372

Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation.

PubMed

Stennard, Fiona A; Costa, Mauro W; Lai, Donna; Biben, Christine; Furtado, Milena B; Solloway, Mark J; McCulley, David J; Leimena, Christiana; Preis, Jost I; Dunwoodie, Sally L; Elliott, David E; Prall, Owen W J; Black, Brian L; Fatkin, Diane; Harvey, Richard P

2005-05-01

The genetic hierarchies guiding lineage specification and morphogenesis of the mammalian embryonic heart are poorly understood. We now show by gene targeting that murine T-box transcription factor Tbx20 plays a central role in these pathways, and has important activities in both cardiac development and adult function. Loss of Tbx20 results in death of embryos at mid-gestation with grossly abnormal heart morphogenesis. Underlying these disturbances was a severely compromised cardiac transcriptional program, defects in the molecular pre-pattern, reduced expansion of cardiac progenitors and a block to chamber differentiation. Notably, Tbx20-null embryos showed ectopic activation of Tbx2 across the whole heart myogenic field. Tbx2 encodes a transcriptional repressor normally expressed in non-chamber myocardium, and in the atrioventricular canal it has been proposed to inhibit chamber-specific gene expression through competition with positive factor Tbx5. Our data demonstrate a repressive activity for Tbx20 and place it upstream of Tbx2 in the cardiac genetic program. Thus, hierarchical, repressive interactions between Tbx20 and other T-box genes and factors underlie the primary lineage split into chamber and non-chamber myocardium in the forming heart, an early event upon which all subsequent morphogenesis depends. Additional roles for Tbx20 in adult heart integrity and contractile function were revealed by in-vivo cardiac functional analysis of Tbx20 heterozygous mutant mice. These data suggest that mutations in human cardiac transcription factor genes, possibly including TBX20, underlie both congenital heart disease and adult cardiomyopathies.

Visual and Vestibular Determinants of Perceived Eye-Level

NASA Technical Reports Server (NTRS)

Cohen, Malcolm Martin

2003-01-01

Both gravitational and optical sources of stimulation combine to determine the perceived elevations of visual targets. The ways in which these sources of stimulation combine with one another in operational aeronautical environments are critical for pilots to make accurate judgments of the relative altitudes of other aircraft and of their own altitude relative to the terrain. In a recent study, my colleagues and I required eighteen observers to set visual targets at their apparent horizon while they experienced various levels of G(sub z) in the human centrifuge at NASA-Ames Research Center. The targets were viewed in darkness and also against specific background optical arrays that were oriented at various angles with respect to the vertical; target settings were lowered as Gz was increased; this effect was reduced when the background optical array was visible. Also, target settings were displaced in the direction that the background optical array was pitched. Our results were attributed to the combined influences of otolith-oculomotor mechanisms that underlie the elevator illusion and visual-oculomotor mechanisms (optostatic responses) that underlie the perceptual effects of viewing pitched optical arrays that comprise the background. In this paper, I present a mathematical model that describes the independent and combined effects of G(sub z) intensity and the orientation and structure of background optical arrays; the model predicts quantitative deviations from normal accurate perceptions of target localization under a variety of conditions. Our earlier experimental results and the mathematical model are described in some detail, and the effects of viewing specific optical arrays under various gravitational-inertial conditions encountered in aeronautical environments are discussed.

Blood flow patterns underlie developmental heart defects

PubMed Central

Midgett, Madeline; Thornburg, Kent

2017-01-01

Although cardiac malformations at birth are typically associated with genetic anomalies, blood flow dynamics also play a crucial role in heart formation. However, the relationship between blood flow patterns in the early embryo and later cardiovascular malformation has not been determined. We used the chicken embryo model to quantify the extent to which anomalous blood flow patterns predict cardiac defects that resemble those in humans and found that restricting either the inflow to the heart or the outflow led to reproducible abnormalities with a dose-response type relationship between blood flow stimuli and the expression of cardiac phenotypes. Constricting the outflow tract by 10–35% led predominantly to ventricular septal defects, whereas constricting by 35–60% most often led to double outlet right ventricle. Ligation of the vitelline vein caused mostly pharyngeal arch artery malformations. We show that both cardiac inflow reduction and graded outflow constriction strongly influence the development of specific and persistent abnormal cardiac structure and function. Moreover, the hemodynamic-associated cardiac defects recapitulate those caused by genetic disorders. Thus our data demonstrate the importance of investigating embryonic blood flow conditions to understand the root causes of congenital heart disease as a prerequisite to future prevention and treatment. NEW & NOTEWORTHY Congenital heart defects result from genetic anomalies, teratogen exposure, and altered blood flow during embryonic development. We show here a novel “dose-response” type relationship between the level of blood flow alteration and manifestation of specific cardiac phenotypes. We speculate that abnormal blood flow may frequently underlie congenital heart defects. PMID:28062416

[Visual acuity in anti-VEGF therapy for AMD : Can specific characteristics in the SD-OCT help?

PubMed

Book, B; Ziegler, M; Heimes, B; Gutfleisch, M; Spital, G; Pauleikhoff, D; Lommatzsch, A

2017-01-01

The efficacy of anti-VEGF therapy in exudative AMD has been established in several large clinical trials using a fixed injection regimen as well as a SD-OCT-based PRN regimen. In these studies, after the first three injections, an increase of the mean visual acuity was observed, which could be stabilized with constant treatment for up to 24 months. However, the specific course of the visual acuity is very different between individuals. The aim of the present study was to correlate specific initial SD-OCT parameters with the course of visual acuity in order to characterize factors that may be important for the individual visual prognosis. In a prospective case study, the visual course and SD-OCT changes of 156 patients with minimum follow-up of 12 months (mean 80.1 months) were analysed. Visual acuity (LogMar) was investigated at regular intervals and correlated with specific SD-OCT parameters (foveal thickness, height of sub-retinal fluid or presence of associated PED, presence of intra-retinal cysts, length of IS/OS break, choroidal thickness). The initial increase in visual acuity could be stabilized over time. This effect was associated with a decrease in foveal retinal thickness, which also persisted over time. While sub-retinal fluid, presence of PED, and choroidal thickness showed no prognostic relevance for the change in visual acuity, the presence of more advanced central retinal thickness, of intra-retinal cysts or a longer break in the IS/OS junction were associated with a less favourable development of visual acuity. In the present study, the presence of more advanced central retinal thickness, of intra-retinal cysts or a larger IS/OS break correlated significantly with a worse visual prognosis. These might be clinical signs for more extensive pre-existing intra-retinal changes. Further analysis and new diagnostic tools may prove this and may result in specific additive neuroprotective or regenerative therapeutic approaches in exudative AMD.

The Association of Multiple Interacting Genes with Specific Phenotypes in Rice Using Gene Coexpression Networks1[C][W][OA

PubMed Central

Ficklin, Stephen P.; Luo, Feng; Feltus, F. Alex

2010-01-01

Discovering gene sets underlying the expression of a given phenotype is of great importance, as many phenotypes are the result of complex gene-gene interactions. Gene coexpression networks, built using a set of microarray samples as input, can help elucidate tightly coexpressed gene sets (modules) that are mixed with genes of known and unknown function. Functional enrichment analysis of modules further subdivides the coexpressed gene set into cofunctional gene clusters that may coexist in the module with other functionally related gene clusters. In this study, 45 coexpressed gene modules and 76 cofunctional gene clusters were discovered for rice (Oryza sativa) using a global, knowledge-independent paradigm and the combination of two network construction methodologies. Some clusters were enriched for previously characterized mutant phenotypes, providing evidence for specific gene sets (and their annotated molecular functions) that underlie specific phenotypes. PMID:20668062

The association of multiple interacting genes with specific phenotypes in rice using gene coexpression networks.

PubMed

Ficklin, Stephen P; Luo, Feng; Feltus, F Alex

2010-09-01

Discovering gene sets underlying the expression of a given phenotype is of great importance, as many phenotypes are the result of complex gene-gene interactions. Gene coexpression networks, built using a set of microarray samples as input, can help elucidate tightly coexpressed gene sets (modules) that are mixed with genes of known and unknown function. Functional enrichment analysis of modules further subdivides the coexpressed gene set into cofunctional gene clusters that may coexist in the module with other functionally related gene clusters. In this study, 45 coexpressed gene modules and 76 cofunctional gene clusters were discovered for rice (Oryza sativa) using a global, knowledge-independent paradigm and the combination of two network construction methodologies. Some clusters were enriched for previously characterized mutant phenotypes, providing evidence for specific gene sets (and their annotated molecular functions) that underlie specific phenotypes.

Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation.

PubMed

Preissl, Sebastian; Fang, Rongxin; Huang, Hui; Zhao, Yuan; Raviram, Ramya; Gorkin, David U; Zhang, Yanxiao; Sos, Brandon C; Afzal, Veena; Dickel, Diane E; Kuan, Samantha; Visel, Axel; Pennacchio, Len A; Zhang, Kun; Ren, Bing

2018-03-01

Analysis of chromatin accessibility can reveal transcriptional regulatory sequences, but heterogeneity of primary tissues poses a significant challenge in mapping the precise chromatin landscape in specific cell types. Here we report single-nucleus ATAC-seq, a combinatorial barcoding-assisted single-cell assay for transposase-accessible chromatin that is optimized for use on flash-frozen primary tissue samples. We apply this technique to the mouse forebrain through eight developmental stages. Through analysis of more than 15,000 nuclei, we identify 20 distinct cell populations corresponding to major neuronal and non-neuronal cell types. We further define cell-type-specific transcriptional regulatory sequences, infer potential master transcriptional regulators and delineate developmental changes in forebrain cellular composition. Our results provide insight into the molecular and cellular dynamics that underlie forebrain development in the mouse and establish technical and analytical frameworks that are broadly applicable to other heterogeneous tissues.

Cellular and molecular mechanisms of HIV-1 integration targeting.

PubMed

Engelman, Alan N; Singh, Parmit K

2018-07-01

Integration is central to HIV-1 replication and helps mold the reservoir of cells that persists in AIDS patients. HIV-1 interacts with specific cellular factors to target integration to interior regions of transcriptionally active genes within gene-dense regions of chromatin. The viral capsid interacts with several proteins that are additionally implicated in virus nuclear import, including cleavage and polyadenylation specificity factor 6, to suppress integration into heterochromatin. The viral integrase protein interacts with transcriptional co-activator lens epithelium-derived growth factor p75 to principally position integration within gene bodies. The integrase additionally senses target DNA distortion and nucleotide sequence to help fine-tune the specific phosphodiester bonds that are cleaved at integration sites. Research into virus-host interactions that underlie HIV-1 integration targeting has aided the development of a novel class of integrase inhibitors and may help to improve the safety of viral-based gene therapy vectors.

Dysfunction of Rapid Neural Adaptation in Dyslexia.

PubMed

Perrachione, Tyler K; Del Tufo, Stephanie N; Winter, Rebecca; Murtagh, Jack; Cyr, Abigail; Chang, Patricia; Halverson, Kelly; Ghosh, Satrajit S; Christodoulou, Joanna A; Gabrieli, John D E

2016-12-21

Identification of specific neurophysiological dysfunctions resulting in selective reading difficulty (dyslexia) has remained elusive. In addition to impaired reading development, individuals with dyslexia frequently exhibit behavioral deficits in perceptual adaptation. Here, we assessed neurophysiological adaptation to stimulus repetition in adults and children with dyslexia for a wide variety of stimuli, spoken words, written words, visual objects, and faces. For every stimulus type, individuals with dyslexia exhibited significantly diminished neural adaptation compared to controls in stimulus-specific cortical areas. Better reading skills in adults and children with dyslexia were associated with greater repetition-induced neural adaptation. These results highlight a dysfunction of rapid neural adaptation as a core neurophysiological difference in dyslexia that may underlie impaired reading development. Reduced neurophysiological adaptation may relate to prior reports of reduced behavioral adaptation in dyslexia and may reveal a difference in brain functions that ultimately results in a specific reading impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

Developing learning environments which support early algebraic reasoning: a case from a New Zealand primary classroom

NASA Astrophysics Data System (ADS)

Hunter, Jodie

2014-12-01

Current reforms in mathematics education advocate the development of mathematical learning communities in which students have opportunities to engage in mathematical discourse and classroom practices which underlie algebraic reasoning. This article specifically addresses the pedagogical actions teachers take which structure student engagement in dialogical discourse and activity which facilitates early algebraic reasoning. Using videotaped recordings of classroom observations, the teacher and researcher collaboratively examined the classroom practices and modified the participatory practices to develop a learning environment which supported early algebraic reasoning. Facilitating change in the classroom environment was a lengthy process which required consistent and ongoing attention initially to the social norms and then to the socio-mathematical norms. Specific pedagogical actions such as the use of specifically designed tasks, materials and representations and a constant press for justification and generalisation were required to support students to link their numerical understandings to algebraic reasoning.

The effects of music genre on young people's alcohol consumption: an experimental observational study.

PubMed

Engels, Rutger C M E; Poelen, Evelien A P; Spijkerman, Renske; Ter Bogt, Tom

2012-01-01

The aim of this study was to test whether exposure to specific music genres in a social drinking setting leads to differences in drinking levels. An observational experimental design was used in which we invited peer groups of young adults into a bar lab, a lab which is furnished like an ordinary, small pub. Between two tasks, people had a break of 50 minutes in which they could order nonalcoholic and alcoholic beverages. During the break, participants were exposed to a specific music genre: popular, hard rock, rap, or classical music. Those groups who were exposed to classical music drank significantly more alcohol than those who were exposed to other music genres. This pattern is quite robust and does not depend on participants' sex or age, drinking habits, own music preference, and relative importance of music in participant's lives. The study's limitations are mentioned.

Retributive and restorative justice.

PubMed

Wenzel, Michael; Okimoto, Tyler G; Feather, Norman T; Platow, Michael J

2008-10-01

The emergence of restorative justice as an alternative model to Western, court-based criminal justice may have important implications for the psychology of justice. It is proposed that two different notions of justice affect responses to rule-breaking: restorative and retributive justice. Retributive justice essentially refers to the repair of justice through unilateral imposition of punishment, whereas restorative justice means the repair of justice through reaffirming a shared value-consensus in a bilateral process. Among the symbolic implications of transgressions, concerns about status and power are primarily related to retributive justice and concerns about shared values are primarily related to restorative justice. At the core of these processes, however, lies the parties' construal of their identity relation, specifically whether or not respondents perceive to share an identity with the offender. The specific case of intergroup transgressions is discussed, as are implications for future research on restoring a sense of justice after rule-breaking.

Suppression of genetic recombination in the pseudoautosomal region and at subtelomeres in mice with a hypomorphic Spo11 allele.

PubMed

Smagulova, Fatima; Brick, Kevin; Pu, Yongmei; Sengupta, Uttara; Camerini-Otero, R Daniel; Petukhova, Galina V

2013-07-22

Homologous recombination is the key process that generates genetic diversity and drives evolution. SPO11 protein triggers recombination by introducing DNA double stranded breaks at discreet areas of the genome called recombination hotspots. The hotspot locations are largely determined by the DNA binding specificity of the PRDM9 protein in human, mice and most other mammals. In budding yeast Saccharomyces cerevisae, which lacks a Prdm9 gene, meiotic breaks are formed opportunistically in the regions of accessible chromatin, primarily at gene promoters. The genome-wide distribution of hotspots in this organism can be altered by tethering Spo11 protein to Gal4 recognition sequences in the strain expressing Spo11 attached to the DNA binding domain of the Gal4 transcription factor. To establish whether similar re-targeting of meiotic breaks can be achieved in PRDM9-containing organisms we have generated a Gal4BD-Spo11 mouse that expresses SPO11 protein joined to the DNA binding domain of yeast Gal4. We have mapped the genome-wide distribution of the recombination initiation sites in the Gal4BD-Spo11 mice. More than two hundred of the hotspots in these mice were novel and were likely defined by Gal4BD, as the Gal4 consensus motif was clustered around the centers in these hotspots. Surprisingly, meiotic DNA breaks in the Gal4BD-Spo11 mice were significantly depleted near the ends of chromosomes. The effect is particularly striking at the pseudoautosomal region of the X and Y chromosomes - normally the hottest region in the genome. Our data suggest that specific, yet-unidentified factors influence the initiation of meiotic recombination at subtelomeric chromosomal regions.

Defining Nitrogen Kinetics for Air Break in Prebreathe

NASA Technical Reports Server (NTRS)

Conkin, Johnny

2009-01-01

Actual tissue nitrogen (N2) kinetics are complex; the uptake and elimination is often approximated with a single half-time compartment in statistical descriptions of denitrogenation [prebreathe (PB)] protocols. Air breaks during PB complicate N2 kinetics. A comparison of symmetrical versus asymmetrical N2 kinetics was performed using the time to onset of hypobaric decompression sickness (DCS) as a surrogate for actual venous N2 tension. Published results of 12 tests involving 179 hypobaric exposures in altitude chambers after PB, with and without air breaks, provide the complex protocols from which to model N2 kinetics. DCS survival time for combined control and air breaks were described with an accelerated log logistic model where N2 uptake and elimination before, during, and after the air break was computed with a simple exponential function or a function that changed half-time depending on ambient N2 partial pressure. P1N2-P2 = delta P defined DCS dose for each altitude exposure, where P2 was the test altitude and P1N2 was computed N2 pressure at the beginning of the altitude exposure. The log likelihood (LL) without DCS dose (null model) was -155.6, and improved (best-fit) to -97.2 when dose was defined with a 240 min half-time for both N2 elimination and uptake during the PB. The description of DCS survival time was less precise with asymmetrical N2 kinetics, for example, LL was -98.9 with 240 min half-time elimination and 120 min half-time uptake. The statistical regression described survival time mechanistically linked to symmetrical N2 kinetics during PBs that also included air breaks. The results are data-specific, and additional data may change the conclusion. The regression is useful to compute additional PB time to compensate for an air break in PB within the narrow range of tested conditions.

Genetic and Environmental Architecture of Changes in Episodic Memory from Middle to Late Middle Age

PubMed Central

Panizzon, Matthew S.; Neale, Michael C.; Docherty, Anna R.; Franz, Carol E.; Jacobson, Kristen C.; Toomey, Rosemary; Xian, Hong; Vasilopoulos, Terrie; Rana, Brinda K.; McKenzie, Ruth M.; Lyons, Michael J.; Kremen, William S.

2015-01-01

Episodic memory is a complex construct at both the phenotypic and genetic level. Ample evidence supports age-related cognitive stability and change being accounted for by general and domain-specific factors. We hypothesized that general and specific factors would underlie change even within this single cognitive domain. We examined six measures from three episodic memory tests in a narrow age cohort at middle and late middle age. The factor structure was invariant across occasions. At both timepoints two of three test-specific factors (story recall, design recall) had significant genetic influences independent of the general memory factor. Phenotypic stability was moderate to high, and primarily accounted for by genetic influences, except for one test-specific factor (list learning). Mean change over time was nonsignificant for one test-level factor; one declined; one improved. The results highlight the phenotypic and genetic complexity of memory and memory change, and shed light on an understudied period of life. PMID:25938244

Genetic and environmental architecture of changes in episodic memory from middle to late middle age.

PubMed

Panizzon, Matthew S; Neale, Michael C; Docherty, Anna R; Franz, Carol E; Jacobson, Kristen C; Toomey, Rosemary; Xian, Hong; Vasilopoulos, Terrie; Rana, Brinda K; McKenzie, Ruth; Lyons, Michael J; Kremen, William S

2015-06-01

Episodic memory is a complex construct at both the phenotypic and genetic level. Ample evidence supports age-related cognitive stability and change being accounted for by general and domain-specific factors. We hypothesized that general and specific factors would underlie change even within this single cognitive domain. We examined 6 measures from 3 episodic memory tests in a narrow age cohort at middle and late middle age. The factor structure was invariant across occasions. At both timepoints 2 of 3 test-specific factors (story recall, design recall) had significant genetic influences independent of the general memory factor. Phenotypic stability was moderate to high, and primarily accounted for by genetic influences, except for 1 test-specific factor (list learning). Mean change over time was nonsignificant for 1 test-level factor; 1 declined; 1 improved. The results highlight the phenotypic and genetic complexity of memory and memory change, and shed light on an understudied period of life. (c) 2015 APA, all rights reserved.

Profound Tissue Specificity in Proliferation Control Underlies Cancer Drivers and Aneuploidy Patterns.

PubMed

Sack, Laura Magill; Davoli, Teresa; Li, Mamie Z; Li, Yuyang; Xu, Qikai; Naxerova, Kamila; Wooten, Eric C; Bernardi, Ronald J; Martin, Timothy D; Chen, Ting; Leng, Yumei; Liang, Anthony C; Scorsone, Kathleen A; Westbrook, Thomas F; Wong, Kwok-Kin; Elledge, Stephen J

2018-04-05

Genomics has provided a detailed structural description of the cancer genome. Identifying oncogenic drivers that work primarily through dosage changes is a current challenge. Unrestrained proliferation is a critical hallmark of cancer. We constructed modular, barcoded libraries of human open reading frames (ORFs) and performed screens for proliferation regulators in multiple cell types. Approximately 10% of genes regulate proliferation, with most performing in an unexpectedly highly tissue-specific manner. Proliferation drivers in a given cell type showed specific enrichment in somatic copy number changes (SCNAs) from cognate tumors and helped predict aneuploidy patterns in those tumors, implying that tissue-type-specific genetic network architectures underlie SCNA and driver selection in different cancers. In vivo screening confirmed these results. We report a substantial contribution to the catalog of SCNA-associated cancer drivers, identifying 147 amplified and 107 deleted genes as potential drivers, and derive insights about the genetic network architecture of aneuploidy in tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

A model study of sediment transport across the shelf break

NASA Astrophysics Data System (ADS)

Marchal, Olivier

2017-04-01

A variety of dynamical processes can contribute to the transport of material (e.g., particulate matter) across the shelf break - the region separating the continental shelf from the continental slope. Among these processes are (i) the reflection of internal waves on the outer shelf and upper slope, and (ii) the instability of hydrographic fronts, roughly aligned with isobaths, that are often present at the shelf break. On the one hand, internal waves reflecting on a sloping boundary can produce bottom shear stresses that are large enough to resuspend non-cohesive sediments into the water column. On the other hand, eddies shed from unstable shelf break fronts can incorporate into their core particle-rich waters from the outer shelf and upper slope, and transport these waters offshore. Here we present numerical experiments with a three-dimensional numerical model of ocean circulation and sediment transport, which illustrate the joint effect of internal waves and eddies on sediment transport across the shelf break. The model is based on the primitive equations and terrain-following coordinates. The model domain is square and idealized, comprising a flat continental shelf, a constant continental slope, and a flat abyssal basin. The model grid has O(1 km) horizontal resolution, so that (sub)mesoscale eddies observed in the vicinity of shelf breaks, such as south of New England, can be represented in detail. Internal waves are excited through the specification of a periodic variation in the across-slope component of velocity at the offshore boundary of the domain, and eddies are generated from the baroclinic instability of a shelf break jet that is initially in strict thermal wind balance. Numerical experiments are conducted that are characterized by (i) different slopes of internal wave characteristics relative to the continental slope, representing sub-critical, critical, and super-critical regimes, and (ii) different values for the dimensionless ratios that emerge from the linear stability analysis of shelf break fronts. Emphasis is placed on the physical conditions that are conducive to the formation and maintenance of bottom and intermediate nepheloid layers - the particle-rich layers that are often observed near oceanic margins in the traces of optical instruments.

[Experience of a Break-Even Point Analysis for Make-or-Buy Decision.].

PubMed

Kim, Yunhee

2006-12-01

Cost containment through continuous quality improvement of medical service is required in an age of a keen competition of the medical market. Laboratory managers should examine the matters on make-or-buy decision periodically. On this occasion, a break-even point analysis can be useful as an analyzing tool. In this study, cost accounting and break-even point (BEP) analysis were performed in case that the immunoassay items showing a recent increase in order volume were to be in-house made. Fixed and variable costs were calculated in case that alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), ferritin, free thyroxine (fT4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), CA 125, CA 19-9, and hepatitis B envelope antibody (HBeAb) were to be tested with Abbott AxSYM instrument. Break-even volume was calculated as fixed cost per year divided by purchasing cost per test minus variable cost per test and BEP ratio as total purchasing costs at break-even volume divided by total purchasing costs at actual annual volume. The average fixed cost per year of AFP, CEA, PSA, ferritin, fT4, T3, TSH, CA 125, CA 19-9, and HBeAb was 8,279,187 won and average variable cost per test, 3,786 won. Average break-even volume was 1,599 and average BEP ratio was 852%. Average BEP ratio without including quality costs such as calibration and quality control was 74%. Because the quality assurance of clinical tests cannot be waived, outsourcing all of 10 items was more adequate than in-house make at the present volume in financial aspect. BEP analysis was useful as a financial tool for make-or-buy decision, the common matter which laboratory managers meet with.

The democratization of gene editing: Insights from site-specific cleavage and double-strand break repair.

PubMed

Jasin, Maria; Haber, James E

2016-08-01

DNA double-strand breaks (DSBs) are dangerous lesions that if not properly repaired can lead to genomic change or cell death. Organisms have developed several pathways and have many factors devoted to repairing DSBs, which broadly occurs by homologous recombination, which relies on an identical or homologous sequence to template repair, or nonhomologous end-joining. Much of our understanding of these repair mechanisms has come from the study of induced DNA cleavage by site-specific endonucleases. In addition to their biological role, these cellular pathways can be co-opted for gene editing to study gene function or for gene therapy or other applications. While the first gene editing experiments were done more than 20 years ago, the recent discovery of RNA-guided endonucleases has simplified approaches developed over the years to make gene editing an approach that is available to the entire biomedical research community. Here, we review DSB repair mechanisms and site-specific cleavage systems that have provided insight into these mechanisms and led to the current gene editing revolution. Copyright © 2016. Published by Elsevier B.V.

The Democratization of Gene Editing: Insights from site-specific cleavage and double-strand break repair

PubMed Central

Jasin, Maria; Haber, James E.

2017-01-01

DNA double-strand breaks (DSBs) are dangerous lesions that if not properly repaired can lead to genomic change or cell death. Organisms have developed several pathways and have many factors devoted to repairing DSBs, which broadly occur by homologous recombination that relies on an identical or homologous sequence to template repair, or nonhomologous end-joining. Much of our understanding of these repair mechanisms has come from the study of induced DNA cleavage by site-specific endonucleases. In addition to their biological role, these cellular pathways can be co-opted for gene editing to study gene function or for gene therapy or other applications. While the first gene editing experiments were done more than 20 years ago, the recent discovery of RNA-guided endonucleases has simplified approaches developed over the years to make gene editing an approach that is available to the entire biomedical research community. Here, we review DSB repair mechanisms and site-specific cleavage systems that have provided insight into these mechanisms and led to the current gene editing revolution. PMID:27261202

Work capacity and anticipation in A.A. Ukhtomsky's concept of dominance

NASA Astrophysics Data System (ADS)

Pavlova, L. P.

2015-08-01

This paper presents the results of theoretical and experimental investigations of human activity and anticipation based on A.A. Ukhtomsky's concept of brain dominance - a non-equilibrium system-forming factor in living systems. Facts on the stages of dominance formation are presented in relation to the creative abilities of the human brain and the role of fatigue as a "lever" for increasing systems' work capacity on the basis of "trace exaltation". Individually, specific features of dominantogenesis are compared with variations in behavioural types. On the basis of chronotopic EEG analysis, we delineate cortical dominants that underlie individual specifics of cognitive processes. The relation is shown between anticipation and the "expansion of dominants" - the broadening of "distal perception" in time and space, as framed by A.A. Ukhtomsky.

Long-Term Synaptic Changes in Two Input Pathways into the Lateral Nucleus of the Amygdala Underlie Fear Extinction

ERIC Educational Resources Information Center

Park, Junchol; Choi, June-Seek

2010-01-01

Plasticity in two input pathways into the lateral nucleus of the amygdala (LA), the medial prefrontal cortex (mPFC) and the sensory thalamus, have been suggested to underlie extinction, suppression of a previously acquired conditioned response (CR) following repeated presentations of the conditioned stimulus (CS). However, little is known about…

Early Phase Endotoxin Tolerance: A Study of the Cellular Mechanisms which Underlie a State of Acquired Refractoriness to Endotoxin-induced Toxic Manifestations

DTIC Science & Technology

1985-12-13

Her leadership , help, and understanding at crltlcal times will always be remembered. Thank you for help ing me attain this great goal and captu~e a...by Braude §1 ~!- (1955) and Cremer and Watson (1957 ) to be the primary site of endotoxin localization following i.v. injection] were st imulated by...A-specif ic tr iggeri ng r eceptor on murine B lymp hocytes. Eur. J. Immunol. 8:63 . Cremer , N. and D.W. Watson. 1957. Inf luence of s tress on

Safety of vitrectomy for floaters.

PubMed

Tan, H Stevie; Mura, Marco; Lesnik Oberstein, Sarit Y; Bijl, Heico M

2011-06-01

To assess the risks of vitrectomy for the removal of primary and secondary vitreous opacities. Retrospective, nonrandomized, interventional case series. We reviewed the results of 116 consecutive cases of vitrectomy for vitreous floaters. Eighty-six cases were primary and 30 cases were secondary floaters. Main outcome measures were the incidence of iatrogenic retinal breaks and postoperative rhegmatogenous retinal detachments. We found iatrogenic retinal breaks in 16.4% of operations. There was no statistically significant difference in risk between cases of primary and secondary floaters. Intraoperative posterior vitreous detachment induction was found to increase significantly the risk of breaks. Retinal detachment occurred in 3 cases (2.5%), all after operations for primary floaters. One case of complicated retinal detachment ended with a low visual acuity of hand movements. Cataract occurred in 50% of phakic cases. Transient postoperative hypotony was found after 5.2% of our operations, and transient postoperative high intraocular pressure was encountered in 7.8%. An intraoperative choroidal hemorrhage occurred in 1 case, which resolved spontaneously. The mean visual acuity improved from 0.20 to 0.13 logarithm of the minimal angle of resolution units. The risk profile of vitrectomy for floaters is comparable with that of vitrectomy for other elective indications. Retinal breaks are a common finding during surgery and treatment of these breaks is crucial for the prevention of postoperative retinal detachment. Patients considering surgery for floaters should be informed specifically about the risks involved. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular and Neuroendocrine Approaches to Understanding Trade-offs: Food, Sex, Aggression, Stress, and Longevity-An Introduction to the Symposium.

PubMed

Schneider, Jill E; Deviche, Pierre

2017-12-01

Life history strategies are composed of multiple fitness components, each of which incurs costs and benefits. Consequently, organisms cannot maximize all fitness components simultaneously. This situation results in a dynamic array of trade-offs in which some fitness traits prevail at the expense of others, often depending on context. The identification of specific constraints and trade-offs has helped elucidate physiological mechanisms that underlie variation in behavioral and physiological life history strategies. There is general recognition that trade-offs are made at the individual and population level, but much remains to be learned concerning the molecular neuroendocrine mechanisms that underlie trade-offs. For example, we still do not know whether the mechanisms that underlie trade-offs at the individual level relate to trade-offs at the population level. To advance our understanding of trade-offs, we organized a group of speakers who study neuroendocrine mechanisms at the interface of traits that are not maximized simultaneously. Speakers were invited to represent research from a wide range of taxa including invertebrates (e.g., worms and insects), fish, nonavian reptiles, birds, and mammals. Three general themes emerged. First, the study of trade-offs requires that we investigate traditional endocrine mechanisms that include hormones, neuropeptides, and their receptors, and in addition, other chemical messengers not traditionally included in endocrinology. The latter group includes growth factors, metabolic intermediates, and molecules of the immune system. Second, the nomenclature and theory of neuroscience that has dominated the study of behavior is being re-evaluated in the face of evidence for the peripheral actions of so-called neuropeptides and neurotransmitters and the behavioral repercussions of these actions. Finally, environmental and ecological contexts continue to be critical in unmasking molecular mechanisms that are hidden when study animals are housed in enclosed spaces, with unlimited food, without competitors or conspecifics, and in constant ambient conditions. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.

Activity of the anterior cingulate cortex and ventral hippocampus underlie increases in contextual fear generalization.

PubMed

Cullen, Patrick K; Gilman, T Lee; Winiecki, Patrick; Riccio, David C; Jasnow, Aaron M

2015-10-01

Memories for context become less specific with time resulting in animals generalizing fear from training contexts to novel contexts. Though much attention has been given to the neural structures that underlie the long-term consolidation of a context fear memory, very little is known about the mechanisms responsible for the increase in fear generalization that occurs as the memory ages. Here, we examine the neural pattern of activation underlying the expression of a generalized context fear memory in male C57BL/6J mice. Animals were context fear conditioned and tested for fear in either the training context or a novel context at recent and remote time points. Animals were sacrificed and fluorescent in situ hybridization was performed to assay neural activation. Our results demonstrate activity of the prelimbic, infralimbic, and anterior cingulate (ACC) cortices as well as the ventral hippocampus (vHPC) underlie expression of a generalized fear memory. To verify the involvement of the ACC and vHPC in the expression of a generalized fear memory, animals were context fear conditioned and infused with 4% lidocaine into the ACC, dHPC, or vHPC prior to retrieval to temporarily inactivate these structures. The results demonstrate that activity of the ACC and vHPC is required for the expression of a generalized fear memory, as inactivation of these regions returned the memory to a contextually precise form. Current theories of time-dependent generalization of contextual memories do not predict involvement of the vHPC. Our data suggest a novel role of this region in generalized memory, which should be incorporated into current theories of time-dependent memory generalization. We also show that the dorsal hippocampus plays a prolonged role in contextually precise memories. Our findings suggest a possible interaction between the ACC and vHPC controls the expression of fear generalization. Copyright © 2015 Elsevier Inc. All rights reserved.

Electrical Arc Ignition Testing for Constellation Program

NASA Technical Reports Server (NTRS)

Sparks, Kyle; Gallus, Timothy; Smith, Sarah

2009-01-01

NASA Johnson Space Center (JSC) Materials and Processes Branch requested that NASA JSC White Sands Test Facility (WSTF) perform testing for the Constellation Program to evaluate the hazard of electrical arc ignition of materials that could be in close proximity to batteries. Specifically, WSTF was requested to perform wire-break electrical arc tests to determine the current threshold for ignition of generic cotton woven fabric samples with a fixed voltage of 3.7 V, a common voltage for hand-held electrical devices. The wire-break test was developed during a previous test program to evaluate the hazard of electrical arc ignition inside the Extravehicular Mobility Unit [1].

A construct divided: prosocial behavior as helping, sharing, and comforting subtypes

PubMed Central

Dunfield, Kristen A.

2014-01-01

The development and maintenance of prosocial, other-oriented behaviors has been of considerable recent interest. Though it is clear that prosocial behaviors emerge early and play a uniquely important role in the social lives of humans, there is less consensus regarding the mechanisms that underlie and maintain these fundamental acts. The goal of this paper is to clarify inconsistencies in our understanding of the early emergence and development of prosocial behavior by proposing a taxonomy of prosocial behavior anchored in the social-cognitive constraints that underlie the ability to act on behalf of others. I will argue that within the general domain of prosocial behavior, other-oriented actions can be categorized into three distinct types (helping, sharing, and comforting) that reflect responses to three distinct negative states (instrumental need, unmet material desire, and emotional distress). In support of this proposal, I will demonstrate that the three varieties of prosocial behavior show unique ages of onset, uncorrelated patterns of production, and distinct patterns of individual differences. Importantly, by differentiating specific varieties of prosocial behavior within the general category, we can begin to explain inconsistencies in the past literature and provide a framework for directing future research into the ontogenetic origins of these essential social behaviors. PMID:25228893

Predictive Coding in Area V4: Dynamic Shape Discrimination under Partial Occlusion

PubMed Central

Choi, Hannah; Pasupathy, Anitha; Shea-Brown, Eric

2018-01-01

The primate visual system has an exquisite ability to discriminate partially occluded shapes. Recent electrophysiological recordings suggest that response dynamics in intermediate visual cortical area V4, shaped by feedback from prefrontal cortex (PFC), may play a key role. To probe the algorithms that may underlie these findings, we build and test a model of V4 and PFC interactions based on a hierarchical predictive coding framework. We propose that probabilistic inference occurs in two steps. Initially, V4 responses are driven solely by bottom-up sensory input and are thus strongly influenced by the level of occlusion. After a delay, V4 responses combine both feedforward input and feedback signals from the PFC; the latter reflect predictions made by PFC about the visual stimulus underlying V4 activity. We find that this model captures key features of V4 and PFC dynamics observed in experiments. Specifically, PFC responses are strongest for occluded stimuli and delayed responses in V4 are less sensitive to occlusion, supporting our hypothesis that the feedback signals from PFC underlie robust discrimination of occluded shapes. Thus, our study proposes that area V4 and PFC participate in hierarchical inference, with feedback signals encoding top-down predictions about occluded shapes. PMID:29566355

The Mirror Neuron System: A Fresh View

PubMed Central

Casile, Antonino; Caggiano, Vittorio; Ferrari, Pier Francesco

2013-01-01

Mirror neurons are a class of visuomotor neurons in the monkey premotor and parietal cortices that discharge during the execution and observation of goal-directed motor acts. They are deemed to be at the basis of primates’ social abilities. In this review, the authors provide a fresh view about two still open questions about mirror neurons. The first question is their possible functional role. By reviewing recent neurophysiological data, the authors suggest that mirror neurons might represent a flexible system that encodes observed actions in terms of several behaviorally relevant features. The second question concerns the possible developmental mechanisms responsible for their initial emergence. To provide a possible answer to question, the authors review two different aspects of sensorimotor development: facial and hand movements, respectively. The authors suggest that possibly two different “mirror” systems might underlie the development of action understanding and imitative abilities in the two cases. More specifically, a possibly prewired system already present at birth but shaped by the social environment might underlie the early development of facial imitative abilities. On the contrary, an experience-dependent system might subserve perception-action couplings in the case of hand movements. The development of this latter system might be critically dependent on the observation of own movements. PMID:21467305

Planning-related motor processes underlie mental practice and imitation learning.

PubMed

Bach, Patric; Allami, Bassem Khalaf; Tucker, Mike; Ellis, Rob

2014-06-01

It is still controversial whether mental practice-the internal rehearsal of movements to improve later performance-relies on processes engaged during physical motor performance and, if so, which processes these are. We report data from 5 experiments, in which participants mentally practiced complex rhythms with either feet or hands while using the same or different body parts to respond to unrelated sounds. We found that responses were impaired for those body parts that were concurrently used in mental practice, suggesting a binding of body-part-specific motor processes to action plans. This result was found when participants mentally trained to memorize the rhythms, to merely improve their performance, when mental practice and execution directly followed one another and when separated by a different task. Finally, it was found irrespective of whether participants practiced on the basis of a symbolic rhythm description and when they practiced by watching somebody perform the rhythms (imitation learning). The effect was eliminated only when the requirement for mental practice was eliminated from the task while keeping visual stimulation identical. These data link mental practice not to execution but planning related motor processes and reveal that these planning processes underlie both mental practice and imitation learning. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Size-Sensitive Perceptual Representations Underlie Visual and Haptic Object Recognition

PubMed Central

Craddock, Matt; Lawson, Rebecca

2009-01-01

A variety of similarities between visual and haptic object recognition suggests that the two modalities may share common representations. However, it is unclear whether such common representations preserve low-level perceptual features or whether transfer between vision and haptics is mediated by high-level, abstract representations. Two experiments used a sequential shape-matching task to examine the effects of size changes on unimodal and crossmodal visual and haptic object recognition. Participants felt or saw 3D plastic models of familiar objects. The two objects presented on a trial were either the same size or different sizes and were the same shape or different but similar shapes. Participants were told to ignore size changes and to match on shape alone. In Experiment 1, size changes on same-shape trials impaired performance similarly for both visual-to-visual and haptic-to-haptic shape matching. In Experiment 2, size changes impaired performance on both visual-to-haptic and haptic-to-visual shape matching and there was no interaction between the cost of size changes and direction of transfer. Together the unimodal and crossmodal matching results suggest that the same, size-specific perceptual representations underlie both visual and haptic object recognition, and indicate that crossmodal memory for objects must be at least partly based on common perceptual representations. PMID:19956685

Gross wood characteristics affecting properties of handsheets made from loblolly pine refiner groundwood

Treesearch

Charles W. McMillin

1968-01-01

Specific refining energy and gross wood properties accounted for as much as 90% of the total variation in strength of handsheets made from 96 pulps disk-refined from chips of varying characteristics. Burst, tear, and breaking length were increased by applying high specific refining energy and using fast-grown wood of high latewood content but of relatively low density...

Ketogenic Diets and Pain

PubMed Central

Masino, Susan A.; Ruskin, David N.

2014-01-01

Ketogenic diets are well-established as a successful anticonvulsant therapy. Based on overlap between mechanisms postulated to underlie pain and inflammation, and mechanisms postulated to underlie therapeutic effects of ketogenic diets, recent studies have explored the ability for ketogenic diets to reduce pain. Here we review clinical and basic research thus far exploring the impact of a ketogenic diet on thermal pain, inflammation, and neuropathic pain. PMID:23680946

Compression selective solid-state chemistry

NASA Astrophysics Data System (ADS)

Hu, Anguang

Compression selective solid-state chemistry refers to mechanically induced selective reactions of solids under thermomechanical extreme conditions. Advanced quantum solid-state chemistry simulations, based on density functional theory with localized basis functions, were performed to provide a remarkable insight into bonding pathways of high-pressure chemical reactions in all agreement with experiments. These pathways clearly demonstrate reaction mechanisms in unprecedented structural details, showing not only the chemical identity of reactive intermediates but also how atoms move along the reaction coordinate associated with a specific vibrational mode, directed by induced chemical stress occurred during bond breaking and forming. It indicates that chemical bonds in solids can break and form precisely under compression as we wish. This can be realized through strongly coupling of mechanical work to an initiation vibrational mode when all other modes can be suppressed under compression, resulting in ultrafast reactions to take place isothermally in a few femtoseconds. Thermodynamically, such reactions correspond to an entropy minimum process on an isotherm where the compression can force thermal expansion coefficient equal to zero. Combining a significantly brief reaction process with specific mode selectivity, both statistical laws and quantum uncertainty principle can be bypassed to precisely break chemical bonds, establishing fundamental principles of compression selective solid-state chemistry. Naturally this leads to understand the ''alchemy'' to purify, grow, and perfect certain materials such as emerging novel disruptive energetics.

BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks.

PubMed

Yan, Winston X; Mirzazadeh, Reza; Garnerone, Silvano; Scott, David; Schneider, Martin W; Kallas, Tomasz; Custodio, Joaquin; Wernersson, Erik; Li, Yinqing; Gao, Linyi; Federova, Yana; Zetsche, Bernd; Zhang, Feng; Bienko, Magda; Crosetto, Nicola

2017-05-12

Precisely measuring the location and frequency of DNA double-strand breaks (DSBs) along the genome is instrumental to understanding genomic fragility, but current methods are limited in versatility, sensitivity or practicality. Here we present Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1) direct labelling of DSBs in fixed cells or tissue sections on a solid surface; (2) low-input requirement by linear amplification of tagged DSBs by in vitro transcription; (3) quantification of DSBs through unique molecular identifiers; and (4) easy scalability and multiplexing. We apply BLISS to profile endogenous and exogenous DSBs in low-input samples of cancer cells, embryonic stem cells and liver tissue. We demonstrate the sensitivity of BLISS by assessing the genome-wide off-target activity of two CRISPR-associated RNA-guided endonucleases, Cas9 and Cpf1, observing that Cpf1 has higher specificity than Cas9. Our results establish BLISS as a versatile, sensitive and efficient method for genome-wide DSB mapping in many applications.

Strongly coupled gauge theories: What can lattice calculations teach us?

NASA Astrophysics Data System (ADS)

Hasenfratz, A.; Brower, R. C.; Rebbi, C.; Weinberg, E.; Witzel, O.

2017-12-01

The dynamical origin of electroweak symmetry breaking is an open question with many possible theoretical explanations. Strongly coupled systems predicting the Higgs boson as a bound state of a new gauge-fermion interaction form one class of candidate models. Due to increased statistics, LHC run II will further constrain the phenomenologically viable models in the near future. In the meanwhile it is important to understand the general properties and specific features of the different competing models. In this work we discuss many-flavor gauge-fermion systems that contain both massless (light) and massive fermions. The former provide Goldstone bosons and trigger electroweak symmetry breaking, while the latter indirectly influence the infrared dynamics. Numerical results reveal that such systems can exhibit a light 0++ isosinglet scalar, well separated from the rest of the spectrum. Further, when we set the scale via the vev of electroweak symmetry breaking, we predict a 2 TeV vector resonance which could be a generic feature of SU(3) gauge theories.

A comparison of two different approaches to characterizing the heterogeneity within antisocial behavior: age-of-onset versus behavioral sub-types.

PubMed

Burt, S Alexandra; Hopwood, Christopher J

2010-04-01

There are two common approaches to sub-typing the well-documented heterogeneity within antisocial behavior: age-of-onset (i.e., child-onset versus adolescent-onset; see Moffitt, 1993) and behavioral (i.e., physical aggression versus nonaggressive rule-breaking). These approaches appear to be intimately connected, such that aggression is particularly characteristic of child-onset antisocial behavior whereas rule-breaking is largely specific to adolescent-onset antisocial behavior (see Moffitt, 2003). Even so, it remains unclear which approach, if either, substantively drives these different manifestations of antisocial behavior. We examined this question in a sample of 1,726 adults in treatment for alcoholism, evaluating the two approaches in regards to their prediction of anger and alcohol dependency. Although age-of-onset predicted both outcomes when analyzed alone, these associations fully dissipated once we controlled for aggression and rule-breaking. Such findings suggest that the behavioral sub-types may prove to be a stronger predictor of antisocial behavior outcomes than is age-of-onset.

Charge ordering and scattering pre-peaks in ionic liquids and alcohols.

PubMed

Perera, Aurélien

2017-01-04

The structural properties of ionic liquids and alcohols are viewed under the charge ordering process as a common basis to explain the peculiarity of their radiation scattering properties, namely the presence, or absence, of a scattering pre-peak. Through the analysis of models, it is shown that the presence, or absence, of a radiation scattering pre-peak is principally related to the symmetry breaking, or not, of the global charge order, induced by the peculiarities of the molecular shapes. This symmetry breaking is achieved, in practice, by the emergence of specific types of clusters, which manifests how the global charge order has changed into a local form. Various atom-atom correlations witness the symmetry breaking induced by this re organization, and this is manifested into a pre-peak in the structure factor. This approach explains why associated liquids such as water do not show a scattering pre-peak. It also explains under which conditions core-soft models can mimic associating liquids.

The CAF-1 and Hir Histone Chaperones Associate with Sites of Meiotic Double-Strand Breaks in Budding Yeast

PubMed Central

Brachet, Elsa; Béneut, Claire; Serrentino, Maria-Elisabetta; Borde, Valérie

2015-01-01

In the meiotic prophase, programmed DNA double-strand breaks (DSB) are introduced along chromosomes to promote homolog pairing and recombination. Although meiotic DSBs usually occur in nucleosome-depleted, accessible regions of chromatin, their repair by homologous recombination takes place in a nucleosomal environment. Nucleosomes may represent an obstacle for the recombination machinery and their timely eviction and reincorporation into chromatin may influence the outcome of recombination, for instance by stabilizing recombination intermediates. Here we show in budding yeast that nucleosomes flanking a meiotic DSB are transiently lost during recombination, and that specific histone H3 chaperones, CAF-1 and Hir, are mobilized at meiotic DSBs. However, the absence of these chaperones has no effect on meiotic recombination, suggesting that timely histone reincorporation following their eviction has no influence on the recombination outcome, or that redundant pathways are activated. This study is the first example of the involvement of histone H3 chaperones at naturally occurring, developmentally programmed DNA double-strand breaks. PMID:25938567

Consensus guidelines for the detection of immunogenic cell death

PubMed Central

Kepp, Oliver; Senovilla, Laura; Vitale, Ilio; Vacchelli, Erika; Adjemian, Sandy; Agostinis, Patrizia; Apetoh, Lionel; Aranda, Fernando; Barnaba, Vincenzo; Bloy, Norma; Bracci, Laura; Breckpot, Karine; Brough, David; Buqué, Aitziber; Castro, Maria G.; Cirone, Mara; Colombo, Maria I.; Cremer, Isabelle; Demaria, Sandra; Dini, Luciana; Eliopoulos, Aristides G.; Faggioni, Alberto; Formenti, Silvia C.; Fučíková, Jitka; Gabriele, Lucia; Gaipl, Udo S.; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giese, Nathalia A.; Guo, Zong Sheng; Hemminki, Akseli; Herrmann, Martin; Hodge, James W.; Holdenrieder, Stefan; Honeychurch, Jamie; Hu, Hong-Min; Huang, Xing; Illidge, Tim M.; Kono, Koji; Korbelik, Mladen; Krysko, Dmitri V.; Loi, Sherene; Lowenstein, Pedro R.; Lugli, Enrico; Ma, Yuting; Madeo, Frank; Manfredi, Angelo A.; Martins, Isabelle; Mavilio, Domenico; Menger, Laurie; Merendino, Nicolò; Michaud, Michael; Mignot, Gregoire; Mossman, Karen L.; Multhoff, Gabriele; Oehler, Rudolf; Palombo, Fabio; Panaretakis, Theocharis; Pol, Jonathan; Proietti, Enrico; Ricci, Jean-Ehrland; Riganti, Chiara; Rovere-Querini, Patrizia; Rubartelli, Anna; Sistigu, Antonella; Smyth, Mark J.; Sonnemann, Juergen; Spisek, Radek; Stagg, John; Sukkurwala, Abdul Qader; Tartour, Eric; Thorburn, Andrew; Thorne, Stephen H.; Vandenabeele, Peter; Velotti, Francesca; Workenhe, Samuel T.; Yang, Haining; Zong, Wei-Xing; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2014-01-01

Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named “immunogenic cell death” (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine. PMID:25941621

Dissociations between developmental dyslexias and attention deficits

PubMed Central

Lukov, Limor; Friedmann, Naama; Shalev, Lilach; Khentov-Kraus, Lilach; Shalev, Nir; Lorber, Rakefet; Guggenheim, Revital

2014-01-01

We examine whether attention deficits underlie developmental dyslexia, or certain types of dyslexia, by presenting double dissociations between the two. We took into account the existence of distinct types of dyslexia and of attention deficits, and focused on dyslexias that may be thought to have an attentional basis: letter position dyslexia (LPD), in which letters migrate within words, attentional dyslexia (AD), in which letters migrate between words, neglect dyslexia, in which letters on one side of the word are omitted or substituted, and surface dyslexia, in which words are read via the sublexical route. We tested 110 children and adults with developmental dyslexia and/or attention deficits, using extensive batteries of reading and attention. For each participant, the existence of dyslexia and the dyslexia type were tested using reading tests that included stimuli sensitive to the various dyslexia types. Attention deficit and its type was established through attention tasks assessing sustained, selective, orienting, and executive attention functioning. Using this procedure, we identified 55 participants who showed a double dissociation between reading and attention: 28 had dyslexia with normal attention and 27 had attention deficits with normal reading. Importantly, each dyslexia with suspected attentional basis dissociated from attention: we found 21 individuals with LPD, 13 AD, 2 neglect dyslexia, and 12 surface dyslexia without attention deficits. Other dyslexia types (vowel dyslexia, phonological dyslexia, visual dyslexia) also dissociated from attention deficits. Examination of 55 additional individuals with both a specific dyslexia and a certain attention deficit found no attention function that was consistently linked with any dyslexia type. Specifically, LPD and AD dissociated from selective attention, neglect dyslexia dissociated from orienting, and surface dyslexia dissociated from sustained and executive attention. These results indicate that visuospatial attention deficits do not underlie these dyslexias. PMID:25628578

Dissociations between developmental dyslexias and attention deficits.

PubMed

Lukov, Limor; Friedmann, Naama; Shalev, Lilach; Khentov-Kraus, Lilach; Shalev, Nir; Lorber, Rakefet; Guggenheim, Revital

2014-01-01

We examine whether attention deficits underlie developmental dyslexia, or certain types of dyslexia, by presenting double dissociations between the two. We took into account the existence of distinct types of dyslexia and of attention deficits, and focused on dyslexias that may be thought to have an attentional basis: letter position dyslexia (LPD), in which letters migrate within words, attentional dyslexia (AD), in which letters migrate between words, neglect dyslexia, in which letters on one side of the word are omitted or substituted, and surface dyslexia, in which words are read via the sublexical route. We tested 110 children and adults with developmental dyslexia and/or attention deficits, using extensive batteries of reading and attention. For each participant, the existence of dyslexia and the dyslexia type were tested using reading tests that included stimuli sensitive to the various dyslexia types. Attention deficit and its type was established through attention tasks assessing sustained, selective, orienting, and executive attention functioning. Using this procedure, we identified 55 participants who showed a double dissociation between reading and attention: 28 had dyslexia with normal attention and 27 had attention deficits with normal reading. Importantly, each dyslexia with suspected attentional basis dissociated from attention: we found 21 individuals with LPD, 13 AD, 2 neglect dyslexia, and 12 surface dyslexia without attention deficits. Other dyslexia types (vowel dyslexia, phonological dyslexia, visual dyslexia) also dissociated from attention deficits. Examination of 55 additional individuals with both a specific dyslexia and a certain attention deficit found no attention function that was consistently linked with any dyslexia type. Specifically, LPD and AD dissociated from selective attention, neglect dyslexia dissociated from orienting, and surface dyslexia dissociated from sustained and executive attention. These results indicate that visuospatial attention deficits do not underlie these dyslexias.

Loss of the imprinted snoRNA mbii-52 leads to increased 5htr2c pre-RNA editing and altered 5HT2CR-mediated behaviour.

PubMed

Doe, Christine M; Relkovic, Dinko; Garfield, Alastair S; Dalley, Jeffrey W; Theobald, David E H; Humby, Trevor; Wilkinson, Lawrence S; Isles, Anthony R

2009-06-15

The Prader-Willi syndrome (PWS) genetic interval contains several brain-expressed small nucleolar (sno)RNA species that are subject to genomic imprinting. In vitro studies have shown that one of these snoRNA molecules, h/mbii-52, negatively regulates editing and alternative splicing of the serotonin 2C receptor (5htr2c) pre-RNA. However, the functional consequences of loss of h/mbii-52 and subsequent increased post-transcriptional modification of 5htr2c are unknown. 5HT2CRs are important in controlling aspects of cognition and the cessation of feeding, and disruption of their function may underlie some of the psychiatric and feeding abnormalities seen in PWS. In a mouse model for PWS lacking expression of mbii-52 (PWS-IC+/-), we show an increase in editing, but not alternative splicing, of the 5htr2c pre-RNA. This change in post-transcriptional modification is associated with alterations in a number of 5HT2CR-related behaviours, including impulsive responding, locomotor activity and reactivity to palatable foodstuffs. In a non-5HT2CR-related behaviour, marble burying, loss of mbii-52 was without effect. The specificity of the behavioural effects to changes in 5HT2CR function was further confirmed using drug challenges. These data illustrate, for the first time, the physiological consequences of altered RNA editing of 5htr2c linked to mbii-52 loss that may underlie specific aspects of the complex PWS phenotype and point to an important functional role for this imprinted snoRNA.

Two-Tailed Comet Assay (2T-Comet): Simultaneous Detection of DNA Single and Double Strand Breaks.

PubMed

Cortés-Gutiérrez, Elva I; Fernández, José Luis; Dávila-Rodríguez, Martha I; López-Fernández, Carmen; Gosálvez, Jaime

2017-01-01

A modification of the original comet assay was developed for the simultaneous evaluation of DNA single strand breaks (SSBs) and double strand breaks (DSBs) in human spermatozoa. The two-dimensional perpendicular tail comet assay (2T-comet) combines non-denaturing and denaturant conditions to the same sperm nucleoid. In this case, the species-specific deproteinized sperm is first subjected to an electrophoretic field under non-denaturing conditions to mobilize isolated free discrete DNA fragments produced from DSBs; this is then followed by a second electrophoresis running perpendicular to the first one but under alkaline conditions to produce DNA denaturation, exposing SSBs on the same linear DNA chain or DNA fragments flanked by DSBs. This procedure results in a two dimensional comet tail emerging from the core where two types of original DNA affected molecule can be simultaneously discriminated. The 2T-comet is a fast, sensitive, and reliable procedure to distinguish between single and double strand DNA damage within the same cell. It is an innovative method for assessing sperm DNA integrity, which has important implications for human fertility and andrological pathology. This technique may be adapted to assess different DNA break types in other species and other cell types.

Oligosyndactylism Mice Have an Inversion of Chromosome 8

PubMed Central

Wise, Thomas L.; Pravtcheva, Dimitrina D.

2004-01-01

The radiation-induced mutation Oligosyndactylism (Os) is associated with limb and kidney defects in heterozygotes and with mitotic arrest and embryonic lethality in homozygotes. We reported that the cell cycle block in Os and in the 94-A/K transgene-induced mutations is due to disruption of the Anapc10 (Apc10/Doc1) gene. To understand the genetic basis of the limb and kidney abnormalities in Os mice we characterized the structural changes of chromosome 8 associated with this mutation. We demonstrate that the Os chromosome 8 has suffered two breaks that are 5 cM (∼10 Mb) apart and the internal fragment delineated by the breaks is in an inverted orientation on the mutant chromosome. While sequences in proximity to the distal break are present in an abnormal Os-specific Anapc10 hybrid transcript, transcription of these sequences in normal mice is low and difficult to detect. Transfer of the Os mutation onto an FVB/N background indicated that the absence of dominant effects in 94-A/K mice is not due to strain background effects on the mutation. Further analysis of this mutation will determine if a gene interrupted by the break or a long-range effect of the rearrangement on neighboring genes is responsible for the dominant effects of Os. PMID:15611179

Oxidant-induced DNA damage of target cells.

PubMed Central

Schraufstätter, I; Hyslop, P A; Jackson, J H; Cochrane, C G

1988-01-01

In this study we examined the leukocytic oxidant species that induce oxidant damage of DNA in whole cells. H2O2 added extracellularly in micromolar concentrations (10-100 microM) induced DNA strand breaks in various target cells. The sensitivity of a specific target cell was inversely correlated to its catalase content and the rate of removal of H2O2 by the target cell. Oxidant species produced by xanthine oxidase/purine or phorbol myristate acetate-stimulated monocytes induced DNA breakage of target cells in proportion to the amount of H2O2 generated. These DNA strand breaks were prevented by extracellular catalase, but not by superoxide dismutase. Cytotoxic doses of HOCl, added to target cells, did not induce DNA strand breakage, and myeloperoxidase added extracellularly in the presence of an H2O2-generating system, prevented the formation of DNA strand breaks in proportion to its H2O2 degrading capacity. The studies also indicated that H2O2 formed hydroxyl radical (.OH) intracellularly, which appeared to be the most likely free radical responsible for DNA damage: .OH was detected in cells exposed to H2O2; the DNA base, deoxyguanosine, was hydroxylated in cells exposed to H2O2; and intracellular iron was essential for induction of DNA strand breaks. PMID:2843565

Breaking cover: neural responses to slow and fast camouflage-breaking motion.

PubMed

Yin, Jiapeng; Gong, Hongliang; An, Xu; Chen, Zheyuan; Lu, Yiliang; Andolina, Ian M; McLoughlin, Niall; Wang, Wei

2015-08-22

Primates need to detect and recognize camouflaged animals in natural environments. Camouflage-breaking movements are often the only visual cue available to accomplish this. Specifically, sudden movements are often detected before full recognition of the camouflaged animal is made, suggesting that initial processing of motion precedes the recognition of motion-defined contours or shapes. What are the neuronal mechanisms underlying this initial processing of camouflaged motion in the primate visual brain? We investigated this question using intrinsic-signal optical imaging of macaque V1, V2 and V4, along with computer simulations of the neural population responses. We found that camouflaged motion at low speed was processed as a direction signal by both direction- and orientation-selective neurons, whereas at high-speed camouflaged motion was encoded as a motion-streak signal primarily by orientation-selective neurons. No population responses were found to be invariant to the camouflage contours. These results suggest that the initial processing of camouflaged motion at low and high speeds is encoded as direction and motion-streak signals in primate early visual cortices. These processes are consistent with a spatio-temporal filter mechanism that provides for fast processing of motion signals, prior to full recognition of camouflage-breaking animals. © 2015 The Authors.

Breaking cover: neural responses to slow and fast camouflage-breaking motion

PubMed Central

Yin, Jiapeng; Gong, Hongliang; An, Xu; Chen, Zheyuan; Lu, Yiliang; Andolina, Ian M.; McLoughlin, Niall; Wang, Wei

2015-01-01

Primates need to detect and recognize camouflaged animals in natural environments. Camouflage-breaking movements are often the only visual cue available to accomplish this. Specifically, sudden movements are often detected before full recognition of the camouflaged animal is made, suggesting that initial processing of motion precedes the recognition of motion-defined contours or shapes. What are the neuronal mechanisms underlying this initial processing of camouflaged motion in the primate visual brain? We investigated this question using intrinsic-signal optical imaging of macaque V1, V2 and V4, along with computer simulations of the neural population responses. We found that camouflaged motion at low speed was processed as a direction signal by both direction- and orientation-selective neurons, whereas at high-speed camouflaged motion was encoded as a motion-streak signal primarily by orientation-selective neurons. No population responses were found to be invariant to the camouflage contours. These results suggest that the initial processing of camouflaged motion at low and high speeds is encoded as direction and motion-streak signals in primate early visual cortices. These processes are consistent with a spatio-temporal filter mechanism that provides for fast processing of motion signals, prior to full recognition of camouflage-breaking animals. PMID:26269500

Chromatin Folding, Fragile Sites, and Chromosome Aberrations Induced by Low- and High- LET Radiation

NASA Technical Reports Server (NTRS)

Zhang, Ye; Cox, Bradley; Asaithamby, Aroumougame; Chen, David J.; Wu, Honglu

2013-01-01

We previously demonstrated non-random distributions of breaks involved in chromosome aberrations induced by low- and high-LET radiation. To investigate the factors contributing to the break point distribution in radiation-induced chromosome aberrations, human epithelial cells were fixed in G1 phase. Interphase chromosomes were hybridized with a multicolor banding in situ hybridization (mBAND) probe for chromosome 3 which distinguishes six regions of the chromosome in separate colors. After the images were captured with a laser scanning confocal microscope, the 3-dimensional structure of interphase chromosome 3 was reconstructed at multimega base pair scale. Specific locations of the chromosome, in interphase, were also analyzed with bacterial artificial chromosome (BAC) probes. Both mBAND and BAC studies revealed non-random folding of chromatin in interphase, and suggested association of interphase chromatin folding to the radiation-induced chromosome aberration hotspots. We further investigated the distribution of genes, as well as the distribution of breaks found in tumor cells. Comparisons of these distributions to the radiation hotspots showed that some of the radiation hotspots coincide with the frequent breaks found in solid tumors and with the fragile sites for other environmental toxins. Our results suggest that multiple factors, including the chromatin structure and the gene distribution, can contribute to radiation-induced chromosome aberrations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiogama, Hideo; Imada, Yukiko; Mori, Masato

Here, we describe two unprecedented large (100-member), longterm (61-year) ensembles based on MRI-AGCM3.2, which were driven by historical and non-warming climate forcing. These ensembles comprise the "Database for Policy Decision making for Future climate change (d4PDF)". We compare these ensembles to large ensembles based on another climate model, as well as to observed data, to investigate the influence of anthropogenic activities on historical changes in the numbers of record-breaking events, including: the annual coldest daily minimum temperature (TNn), the annual warmest daily maximum temperature (TXx) and the annual most intense daily precipitation event (Rx1day). These two climate model ensembles indicatemore » that human activity has already had statistically significant impacts on the number of record-breaking extreme events worldwide mainly in the Northern Hemisphere land. Specifically, human activities have altered the likelihood that a wider area globally would suffer record-breaking TNn, TXx and Rx1day events than that observed over the 2001- 2010 period by a factor of at least 0.6, 5.4 and 1.3, respectively. However, we also find that the estimated spatial patterns and amplitudes of anthropogenic impacts on the probabilities of record-breaking events are sensitive to the climate model and/or natural-world boundary conditions used in the attribution studies.« less

WHO ARE THE DISADVANTAGED.

ERIC Educational Resources Information Center

ORNSTEIN, ALLAN C.

THIS ARTICLE DISCUSSES SOME SPECIFIC ASPECTS OF THE INDIVIDUAL, SOCIAL, ENVIRONMENTAL, PARENTAL AND HYGIENIC DEPRIVATIONS OF DISADVANTAGED YOUTH. ALSO NOTED ARE DEPRIVATIONS THAT RESULT FROM RACE, CONSTRICTED EXPERIENCE, AND EDUCATIONAL HANDICAPS. EDUCATION IS CONSIDERED THE MOST IMPORTANT MEANS OF BREAKING THROUGH THE COMPLEX CYCLE OF POVERTY AND…

Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells

PubMed Central

van den Brink, Susanne C.; Baillie-Johnson, Peter; Balayo, Tina; Hadjantonakis, Anna-Katerina; Nowotschin, Sonja; Turner, David A.; Martinez Arias, Alfonso

2014-01-01

Mouse embryonic stem cells (mESCs) are clonal populations derived from preimplantation mouse embryos that can be propagated in vitro and, when placed into blastocysts, contribute to all tissues of the embryo and integrate into the normal morphogenetic processes, i.e. they are pluripotent. However, although they can be steered to differentiate in vitro into all cell types of the organism, they cannot organise themselves into structures that resemble embryos. When aggregated into embryoid bodies they develop disorganised masses of different cell types with little spatial coherence. An exception to this rule is the emergence of retinas and anterior cortex-like structures under minimal culture conditions. These structures emerge from the cultures without any axial organisation. Here, we report that small aggregates of mESCs, of about 300 cells, self-organise into polarised structures that exhibit collective behaviours reminiscent of those that cells exhibit in early mouse embryos, including symmetry breaking, axial organisation, germ layer specification and cell behaviour, as well as axis elongation. The responses are signal specific and uncouple processes that in the embryo are tightly associated, such as specification of the anteroposterior axis and anterior neural development, or endoderm specification and axial elongation. We discuss the meaning and implications of these observations and the potential uses of these structures which, because of their behaviour, we suggest to call ‘gastruloids’. PMID:25371360

Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells.

PubMed

van den Brink, Susanne C; Baillie-Johnson, Peter; Balayo, Tina; Hadjantonakis, Anna-Katerina; Nowotschin, Sonja; Turner, David A; Martinez Arias, Alfonso

2014-11-01

Mouse embryonic stem cells (mESCs) are clonal populations derived from preimplantation mouse embryos that can be propagated in vitro and, when placed into blastocysts, contribute to all tissues of the embryo and integrate into the normal morphogenetic processes, i.e. they are pluripotent. However, although they can be steered to differentiate in vitro into all cell types of the organism, they cannot organise themselves into structures that resemble embryos. When aggregated into embryoid bodies they develop disorganised masses of different cell types with little spatial coherence. An exception to this rule is the emergence of retinas and anterior cortex-like structures under minimal culture conditions. These structures emerge from the cultures without any axial organisation. Here, we report that small aggregates of mESCs, of about 300 cells, self-organise into polarised structures that exhibit collective behaviours reminiscent of those that cells exhibit in early mouse embryos, including symmetry breaking, axial organisation, germ layer specification and cell behaviour, as well as axis elongation. The responses are signal specific and uncouple processes that in the embryo are tightly associated, such as specification of the anteroposterior axis and anterior neural development, or endoderm specification and axial elongation. We discuss the meaning and implications of these observations and the potential uses of these structures which, because of their behaviour, we suggest to call 'gastruloids'. © 2014. Published by The Company of Biologists Ltd.

The RNA surveillance protein SMG1 activates p53 in response to DNA double-strand breaks but not exogenously oxidized mRNA

PubMed Central

Gewandter, Jennifer S; Bambara, Robert A

2011-01-01

DNA damage, stalled replication forks, errors in mRNA splicing and availability of nutrients activate specific phosphatidylinositiol-3-kinase-like kinases (PIKKs) that in turn phosphorylate downstream targets such as p53 on serine 15. While the PIKK proteins ATM and ATR respond to specific DNA lesions, SMG1 responds to errors in mRNA splicing and when cells are exposed to genotoxic stress. Yet, whether genotoxic stress activates SMG1 through specific types of DNA lesions or RNA damage remains poorly understood. Here, we demonstrate that siRNA oligonucleotides targeting the mRNA surveillance proteins SMG1, Upf1, Upf2 or the PIKK protein ATM attenuated p53 (ser15) phosphorylation in cells damaged by high oxygen (hyperoxia), a model of persistent oxidative stress that damages nucleotides. In contrast, loss of SMG1 or ATM, but not Upf1 or Upf2 reduced p53 (ser15) phosphorylation in response to DNA double strand breaks produced by expression of the endonuclease I-PpoI. To determine whether SMG1-dependent activation of p53 was in response to oxidative mRNA damage, mRNA encoding green fluorescence protein (GFP) transcribed in vitro was oxidized by Fenton chemistry and transfected into cells. Although oxidation of GFP mRNA resulted in dose-dependent fragmentation of the mRNA and reduced expression of GFP, it did not stimulate p53 or the p53-target gene p21. These findings establish SMG1 activates p53 in response to DNA double strand breaks independent of the RNA surveillance proteins Upf1 or Upf2; however, these proteins can stimulate p53 in response to oxidative stress but not necessarily oxidized RNA. PMID:21701263

Does Growth in the Executive System of Working Memory Underlie Growth in Literacy for Bilingual Children with and without Reading Disabilities?

ERIC Educational Resources Information Center

Swanson, H. Lee; Orosco, Michael J.; Kudo, Milagros

2017-01-01

This cohort-sequential study explored the components of working memory (WM) that underlie second language (L2) reading growth in 450 children at risk and not at risk for reading disabilities (RD) whose first language is Spanish. English language learners designated as balanced and nonbalanced bilinguals with and without risk for RD in Grades 1, 2,…

Structure-based control of complex networks with nonlinear dynamics.

PubMed

Zañudo, Jorge Gomez Tejeda; Yang, Gang; Albert, Réka

2017-07-11

What can we learn about controlling a system solely from its underlying network structure? Here we adapt a recently developed framework for control of networks governed by a broad class of nonlinear dynamics that includes the major dynamic models of biological, technological, and social processes. This feedback-based framework provides realizable node overrides that steer a system toward any of its natural long-term dynamic behaviors, regardless of the specific functional forms and system parameters. We use this framework on several real networks, identify the topological characteristics that underlie the predicted node overrides, and compare its predictions to those of structural controllability in control theory. Finally, we demonstrate this framework's applicability in dynamic models of gene regulatory networks and identify nodes whose override is necessary for control in the general case but not in specific model instances.

Functional neuroimaging in epileptic encephalopathies.

PubMed

Siniatchkin, Michael; Capovilla, Giuseppe

2013-11-01

Epileptic encephalopathies (EEs) represent a group of severe epileptic disorders associated with cognitive and behavioral disturbances. The mechanisms of cognitive disability in EEs remain unclear. This review summarized neuroimaging studies that have tried to describe specific fingerprints of brain activation in EE. Although the epileptic activity can be generated individually in different brain regions, it seems likely that the activity propagates in a syndrome-specific way. In some EEs, the epileptiform discharges were associated with an interruption of activity in the default mode network. In another EE, other mechanisms seem to underlie cognitive disability associated with epileptic activity, for example, abnormal connectivity pattern or interfering activity in the thalamocortical network. Further neuroimaging studies are needed to investigate the short-term and long-term impact of epileptic activity on cognition and development. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Brain Oscillations, Hypnosis, and Hypnotizability.

PubMed

Jensen, Mark P; Adachi, Tomonori; Hakimian, Shahin

2015-01-01

This article summarizes the state-of-science knowledge regarding the associations between hypnosis and brain oscillations. Brain oscillations represent the combined electrical activity of neuronal assemblies, usually measured as specific frequencies representing slower (delta, theta, alpha) and faster (beta, gamma) oscillations. Hypnosis has been most closely linked to power in the theta band and changes in gamma activity. These oscillations are thought to play a critical role in both the recording and recall of declarative memory and emotional limbic circuits. The authors propose that this role may be the mechanistic link between theta (and perhaps gamma) oscillations and hypnosis, specifically, that the increases in theta oscillations and changes in gamma activity observed with hypnosis may underlie some hypnotic responses. If these hypotheses are supported, they have important implications for both understanding the effects of hypnosis and for enhancing response to hypnotic treatments.

Population Ancestry and Genetic Risk for Diabetes and Kidney, Cardiovascular, and Bone Disease: Modifiable Environmental Factors May Produce the Cures

PubMed Central

Freedman, Barry I.; Divers, Jasmin; Palmer, Nicholette D.

2013-01-01

Variable rates of disease observed between members of different continental population groups may be mediated by inherited factors, environmental exposures, or their combination. This manuscript provides evidence in support of differential allele frequency distributions that underlie the higher rates of non-diabetic kidney disease in the focal segmental glomerulosclerosis spectrum of disease and lower rates of coronary artery calcified atherosclerotic plaque and osteoporosis in populations of African ancestry. With recognition that these and other common complex diseases are affected by biologic factors comes the realization that targeted manipulation of environmental exposures and pharmacologic treatments will have different effects based on genotype. The current era of precision medicine will couple one’s genetic make-up with specific therapies to reduce rates of disease based on presence of disease-specific alleles. PMID:23896482

Gray's Reinforcement Sensitivity Theory as a framework for research on personality-psychopathology associations.

PubMed

Bijttebier, Patricia; Beck, Ilse; Claes, Laurence; Vandereycken, Walter

2009-07-01

Gray's Reinforcement Sensitivity Theory (RST) presupposes individual differences in the sensitivity of basic brain systems that respond to punishing and reinforcing stimuli. These differences are thought to underlie the personality dimensions of anxiety and impulsivity, and to have relevance for psychopathology. The present article aims at reviewing RST-based research on personality-psychopathology associations. First, RST and its revisions are described and the link between RST systems and personality dimensions is discussed. Second, studies investigating associations between RST systems and specific types of psychopathology are summarized. Although the available research yields a rather consistent picture with respect to constellations of BIS/BAS sensitivity that are associated with specific types of psychopathology, it also provides a clear indication that much work remains to be done. The discussion section highlights several topics that deserve future research attention.

Proteomic Approaches in Biomarker Discovery: New Perspectives in Cancer Diagnostics

PubMed Central

Kocevar, Nina; Komel, Radovan

2014-01-01

Despite remarkable progress in proteomic methods, including improved detection limits and sensitivity, these methods have not yet been established in routine clinical practice. The main limitations, which prevent their integration into clinics, are high cost of equipment, the need for highly trained personnel, and last, but not least, the establishment of reliable and accurate protein biomarkers or panels of protein biomarkers for detection of neoplasms. Furthermore, the complexity and heterogeneity of most solid tumours present obstacles in the discovery of specific protein signatures, which could be used for early detection of cancers, for prediction of disease outcome, and for determining the response to specific therapies. However, cancer proteome, as the end-point of pathological processes that underlie cancer development and progression, could represent an important source for the discovery of new biomarkers and molecular targets for tailored therapies. PMID:24550697

Lexical Processing in School-Age Children with Autism Spectrum Disorder and Children with Specific Language Impairment: The Role of Semantics.

PubMed

Haebig, Eileen; Kaushanskaya, Margarita; Ellis Weismer, Susan

2015-12-01

Children with autism spectrum disorder (ASD) and specific language impairment (SLI) often have immature lexical-semantic knowledge; however, the organization of lexical-semantic knowledge is poorly understood. This study examined lexical processing in school-age children with ASD, SLI, and typical development, who were matched on receptive vocabulary. Children completed a lexical decision task, involving words with high and low semantic network sizes and nonwords. Children also completed nonverbal updating and shifting tasks. Children responded more accurately to words from high than from low semantic networks; however, follow-up analyses identified weaker semantic network effects in the SLI group. Additionally, updating and shifting abilities predicted lexical processing, demonstrating similarity in the mechanisms which underlie semantic processing in children with ASD, SLI, and typical development.

Lexical Processing in School-Age Children with Autism Spectrum Disorder and Children with Specific Language Impairment: The Role of Semantics

PubMed Central

Haebig, Eileen; Kaushanskaya, Margarita; Weismer, Susan Ellis

2016-01-01

Children with autism spectrum disorder (ASD) and specific language impairment (SLI) often have immature lexical-semantic knowledge; however, the organization of lexical-semantic knowledge is poorly understood. This study examined lexical processing in school-age children with ASD, SLI, and typical development, who were matched on receptive vocabulary. Children completed a lexical decision task, involving words with high and low semantic network sizes and nonwords. Children also completed nonverbal updating and shifting tasks. Children responded more accurately to words from high than from low semantic networks; however, follow-up analyses identified weaker semantic network effects in the SLI group. Additionally, updating and shifting abilities predicted lexical processing, demonstrating similarity in the mechanisms which underlie semantic processing in children with ASD, SLI, and typical development. PMID:26210517

A Window into the Brain: Advances in Psychiatric fMRI

PubMed Central

Zhan, Xiaoyan

2015-01-01

Functional magnetic resonance imaging (fMRI) plays a key role in modern psychiatric research. It provides a means to assay differences in brain systems that underlie psychiatric illness, treatment response, and properties of brain structure and function that convey risk factor for mental diseases. Here we review recent advances in fMRI methods in general use and progress made in understanding the neural basis of mental illness. Drawing on concepts and findings from psychiatric fMRI, we propose that mental illness may not be associated with abnormalities in specific local regions but rather corresponds to variation in the overall organization of functional communication throughout the brain network. Future research may need to integrate neuroimaging information drawn from different analysis methods and delineate spatial and temporal patterns of brain responses that are specific to certain types of psychiatric disorders. PMID:26413531

Low-Energy Electron-Induced Strand Breaks in Telomere-Derived DNA Sequences-Influence of DNA Sequence and Topology.

PubMed

Rackwitz, Jenny; Bald, Ilko

2018-03-26

During cancer radiation therapy high-energy radiation is used to reduce tumour tissue. The irradiation produces a shower of secondary low-energy (<20 eV) electrons, which are able to damage DNA very efficiently by dissociative electron attachment. Recently, it was suggested that low-energy electron-induced DNA strand breaks strongly depend on the specific DNA sequence with a high sensitivity of G-rich sequences. Here, we use DNA origami platforms to expose G-rich telomere sequences to low-energy (8.8 eV) electrons to determine absolute cross sections for strand breakage and to study the influence of sequence modifications and topology of telomeric DNA on the strand breakage. We find that the telomeric DNA 5'-(TTA GGG) 2 is more sensitive to low-energy electrons than an intermixed sequence 5'-(TGT GTG A) 2 confirming the unique electronic properties resulting from G-stacking. With increasing length of the oligonucleotide (i.e., going from 5'-(GGG ATT) 2 to 5'-(GGG ATT) 4 ), both the variety of topology and the electron-induced strand break cross sections increase. Addition of K + ions decreases the strand break cross section for all sequences that are able to fold G-quadruplexes or G-intermediates, whereas the strand break cross section for the intermixed sequence remains unchanged. These results indicate that telomeric DNA is rather sensitive towards low-energy electron-induced strand breakage suggesting significant telomere shortening that can also occur during cancer radiation therapy. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Global analysis of double-strand break processing reveals in vivo properties of the helicase-nuclease complex AddAB

PubMed Central

Badrinarayanan, Anjana; Cisse, Ibrahim I.

2017-01-01

In bacteria, double-strand break (DSB) repair via homologous recombination is thought to be initiated through the bi-directional degradation and resection of DNA ends by a helicase-nuclease complex such as AddAB. The activity of AddAB has been well-studied in vitro, with translocation speeds between 400–2000 bp/s on linear DNA suggesting that a large section of DNA around a break site is processed for repair. However, the translocation rate and activity of AddAB in vivo is not known, and how AddAB is regulated to prevent excessive DNA degradation around a break site is unclear. To examine the functions and mechanistic regulation of AddAB inside bacterial cells, we developed a next-generation sequencing-based approach to assay DNA processing after a site-specific DSB was introduced on the chromosome of Caulobacter crescentus. Using this assay we determined the in vivo rates of DSB processing by AddAB and found that putative chi sites attenuate processing in a RecA-dependent manner. This RecA-mediated regulation of AddAB prevents the excessive loss of DNA around a break site, limiting the effects of DSB processing on transcription. In sum, our results, taken together with prior studies, support a mechanism for regulating AddAB that couples two key events of DSB repair–the attenuation of DNA-end processing and the initiation of homology search by RecA–thereby helping to ensure that genomic integrity is maintained during DSB repair. PMID:28489851

DNA Double-Strand Breaks Coupled with PARP1 and HNRNPA2B1 Binding Sites Flank Coordinately Expressed Domains in Human Chromosomes

PubMed Central

Fedoseeva, Daria M.; Sosin, Dmitri V.; Grachev, Sergei A.; Serebraykova, Marina V.; Romanenko, Svetlana A.; Vorobieva, Nadezhda V.; Kravatsky, Yuri V.

2013-01-01

Genome instability plays a key role in multiple biological processes and diseases, including cancer. Genome-wide mapping of DNA double-strand breaks (DSBs) is important for understanding both chromosomal architecture and specific chromosomal regions at DSBs. We developed a method for precise genome-wide mapping of blunt-ended DSBs in human chromosomes, and observed non-random fragmentation and DSB hot spots. These hot spots are scattered along chromosomes and delimit protected 50–250 kb DNA domains. We found that about 30% of the domains (denoted forum domains) possess coordinately expressed genes and that PARP1 and HNRNPA2B1 specifically bind DNA sequences at the forum domain termini. Thus, our data suggest a novel type of gene regulation: a coordinated transcription or silencing of gene clusters delimited by DSB hot spots as well as PARP1 and HNRNPa2B1 binding sites. PMID:23593027

Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation

PubMed Central

Devlin, Rebecca; Marques, Catarina A; Paape, Daniel; Prorocic, Marko; Zurita-Leal, Andrea C; Campbell, Samantha J; Lapsley, Craig; Dickens, Nicholas; McCulloch, Richard

2016-01-01

Survival of Trypanosoma brucei depends upon switches in its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation. VSG switching occurs by frequent homologous recombination, which is thought to require locus-specific initiation. Here, we show that a RecQ helicase, RECQ2, acts to repair DNA breaks, including in the telomeric site of VSG expression. Despite this, RECQ2 loss does not impair antigenic variation, but causes increased VSG switching by recombination, arguing against models for VSG switch initiation through direct generation of a DNA double strand break (DSB). Indeed, we show DSBs inefficiently direct recombination in the VSG expression site. By mapping genome replication dynamics, we reveal that the transcribed VSG expression site is the only telomeric site that is early replicating – a differential timing only seen in mammal-infective parasites. Specific association between VSG transcription and replication timing reveals a model for antigenic variation based on replication-derived DNA fragility. DOI: http://dx.doi.org/10.7554/eLife.12765.001 PMID:27228154

DNA Breaks and End Resection Measured Genome-wide by End Sequencing.

PubMed

Canela, Andres; Sridharan, Sriram; Sciascia, Nicholas; Tubbs, Anthony; Meltzer, Paul; Sleckman, Barry P; Nussenzweig, André

2016-09-01

DNA double-strand breaks (DSBs) arise during physiological transcription, DNA replication, and antigen receptor diversification. Mistargeting or misprocessing of DSBs can result in pathological structural variation and mutation. Here we describe a sensitive method (END-seq) to monitor DNA end resection and DSBs genome-wide at base-pair resolution in vivo. We utilized END-seq to determine the frequency and spectrum of restriction-enzyme-, zinc-finger-nuclease-, and RAG-induced DSBs. Beyond sequence preference, chromatin features dictate the repertoire of these genome-modifying enzymes. END-seq can detect at least one DSB per cell among 10,000 cells not harboring DSBs, and we estimate that up to one out of 60 cells contains off-target RAG cleavage. In addition to site-specific cleavage, we detect DSBs distributed over extended regions during immunoglobulin class-switch recombination. Thus, END-seq provides a snapshot of DNA ends genome-wide, which can be utilized for understanding genome-editing specificities and the influence of chromatin on DSB pathway choice. Published by Elsevier Inc.

Utility of γH2AX as a molecular marker of DNA double-strand breaks in nuclear medicine: applications to radionuclide therapy employing auger electron-emitting isotopes.

PubMed

Mah, Li-Jeen; Orlowski, Christian; Ververis, Katherine; El-Osta, Assam; Karagiannis, Tom C

2011-01-01

There is an intense interest in the development of radiopharmaceuticals for cancer therapy. In particular, radiopharmaceuticals which involve targeting radionuclides specifically to cancer cells with the use of monoclonal antibodies (radioimmunotherapy) or peptides (targeted radiotherapy) are being widely investigated. For example, the ultra-short range Auger electron-emitting isotopes, which are discussed in this review, are being considered in the context of DNAtargeted radiotherapy. The efficient quantitative evaluation of the levels of damage caused by such potential radiopharmaceuticals is required for assessment of therapeutic efficacy and determination of relevant doses for successful treatment. The DNA double-strand break surrogate marker, γH2AX, has emerged as a useful biomonitor of damage and thus effectiveness of treatment, offering a highly specific and sensitive means of assessment. This review will cover the potential applications of γH2AX in nuclear medicine, in particular radionuclide therapy.

Stone tool production and utilization by bonobo-chimpanzees (Pan paniscus).

PubMed

Roffman, Itai; Savage-Rumbaugh, Sue; Rubert-Pugh, Elizabeth; Ronen, Avraham; Nevo, Eviatar

2012-09-04

Using direct percussion, language-competent bonobo-chimpanzees Kanzi and Pan-Banisha produced a significantly wider variety of flint tool types than hitherto reported, and used them task-specifically to break wooden logs or to dig underground for food retrieval. For log breaking, small flakes were rotated drill-like or used as scrapers, whereas thick cortical flakes were used as axes or wedges, leaving consistent wear patterns along the glued slits, the weakest areas of the log. For digging underground, a variety of modified stone tools, as well as unmodified flint nodules, were used as shovels. Such tool production and utilization competencies reported here in Pan indicate that present-day Pan exhibits Homo-like technological competencies.

FAST TRACK COMMUNICATION: Criticality-induced universality in ratchets

NASA Astrophysics Data System (ADS)

Chacón, Ricardo

2010-08-01

Conclusive mathematical arguments are presented supporting the ratchet conjecture (Chacón 2007 J. Phys. A: Math. Theor. 40 F413), i.e. the existence of a universal force waveform which optimally enhances directed transport by symmetry breaking. Specifically, such a particular waveform is shown to be unique for both temporal and spatial biharmonic forces, and general (non-perturbative) laws providing the dependence of the strength of directed transport on the force parameters are deduced for these forces. The theory explains previous results for a great diversity of systems subjected to such biharmonic forces and provides a universal quantitative criterion to optimize any application of the ratchet effect induced by symmetry breaking of temporal and spatial biharmonic forces.

A method for assessing the cost-effectiveness and the break-even point of clinical practice guidelines.

PubMed

Gandjour, A; Lauterbach, K W

2001-01-01

Assessing the costs and benefits of developing a clinical practice guideline is important because investments in guidelines compete with investments in other clinical programs. Despite the considerable number of guidelines in many industrialized countries, little is known about their costs and cost-effectiveness. The authors have developed specific measures to determine the cost-effectiveness of guidelines, using a German evidence-based guideline on obesity for the diagnosis and treatment of obese patients as a model. The measures are: the number of people needed to cure, the number of people needed to prevent from developing the disease in question, and the number of people to treat in order to break even.

Deciphering the Landauer-Büttiker Transmission Function from Single Molecule Break Junction Experiments

NASA Astrophysics Data System (ADS)

Reuter, Matthew; Tschudi, Stephen

When investigating the electrical response properties of molecules, experiments often measure conductance whereas computation predicts transmission probabilities. Although the Landauer-Büttiker theory relates the two in the limit of coherent scattering through the molecule, a direct comparison between experiment and computation can still be difficult. Experimental data (specifically that from break junctions) is statistical and computational results are deterministic. Many studies compare the most probable experimental conductance with computation, but such an analysis discards almost all of the experimental statistics. In this work we develop tools to decipher the Landauer-Büttiker transmission function directly from experimental statistics and then apply them to enable a fairer comparison between experimental and computational results.

The cellular immune response of Daphnia magna under host-parasite genetic variation and variation in initial dose

PubMed Central

Auld, Stuart K. J. R; Edel, Kai H.; Little, Tom J.

2013-01-01

In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. PMID:23025616

Randomized Controlled Study to Investigate the Effect of Topical Diquafosol Tetrasodium on Corneal Sensitivity in Short Tear Break-Up Time Dry Eye.

PubMed

Kaido, Minako; Kawashima, Motoko; Shigeno, Yuta; Yamada, Yoshiaki; Tsubota, Kazuo

2018-05-01

Complex mechanisms underlie dry eye (DE) symptom provocation. In particular, corneal hypersensitivity may provoke symptoms in short tear break-up time (BUT) DE characterized by tear film instability. We hypothesized that improved tear film stability may alleviate corneal sensitivity in patients with short tear BUT DE. Therefore, we investigated the effect of topical diquafosol tetrasodium (DQS) on corneal sensitivity in unstable tear film DE. This prospective, randomized study included 27 subjects (age: 39.1 ± 8.4 years; range: 25-59 years) with short tear BUT DE, defined based on the presence of DE symptoms and tear film instability. Subjects were randomly divided into DQS (3% DQS, 12 subjects) and artificial tear (AT; preservative-free AT, 15 subjects) groups. Subjects applied the medication 6 times a day for 5 weeks. The perception of touch (S-touch) and pain (S-pain) sensitivity was measured using a Cochet-Bonnet esthesiometer. Tear evaluation, corneal sensitivity, and DE symptoms were compared before and after DQS or AT administration. The correlation between the improvement degrees of corneal sensitivity and DE symptoms following medication was analyzed. DQS significantly improved tear BUT and tear meniscus height (TMH) scores (p < 0.05), while AT significantly improved tear BUT (p < 0.05) but not TMH score. Mean S-pain and DE symptom scores were lower after medication use in the DQS (S-pain and DE symptoms: p  < 0.05) and AT groups (S-pain: p  = 0.05; DE symptoms: p  < 0.05). However, S-touch did not change significantly in either group. A positive correlation was observed between the improvement degrees of S-pain and DE symptoms in the overall subjects studied. Both DQS and AT alleviate corneal hypersensitivity and DE symptoms in eyes with short tear BUT DE. However, DQS seems to be more effective to adjust tear environment, leading to the normalization of corneal sensitivity and DE symptoms. UMIN Clinical Trials Registry Identifier, UMIN000014536.

Detection of Listeria spp. in liquid egg products and in the egg breaking plants environment and tracking of Listeria monocytogenes by PFGE.

PubMed

Rivoal, Katell; Fablet, Aurore; Courtillon, Céline; Bougeard, Stéphanie; Chemaly, Marianne; Protais, Jocelyne

2013-08-16

Human listeriosis, caused by Listeria monocytogenes, is a severe bacterial infection that can lead to meningitis, cerebromeningitis, bacteremia or septicemia, with acute lethality and potentially leading to death. A study has shown that 29.5% of the caged laying hens in France are contaminated by L. monocytogenes (Chemaly et al., 2008). However, very little information regarding egg and egg product contamination is currently available. The objective of this study is to determine the sanitary status of egg products and egg breaking plants in France regarding Listeria spp. and L. monocytogenes contaminations. The sampling scheme performed in five egg breaking plants in Western France during one year have revealed that 8.5% of raw egg products were contaminated by L. monocytogenes. No pasteurized egg products have been shown to be contaminated by L. monocytogenes. However, a high level of contamination by Listeria spp., and particularly by L. innocua, has been shown with 26.2% and 1.8% of raw and pasteurized egg products contaminated, respectively. This work has also revealed the presence of Listeria spp. and L. monocytogenes in the environment of egg breaking plants with 65.1% and 8.0% of contaminated samples, respectively. The typing of 253 isolates of L. monocytogenes by PFGE using ApaI and AscI enzymes has revealed a high diversity with 46 different pulsotypes and has shown that the raw material is a source of contamination of egg breaking plants. One L. monocytogenes cluster was dominant in the 5 egg-breaking plants during the four seasons studied. The issue of which strains are better adapted to egg products must be considered and studied in depth by comparing them to pulsotypes from strains of other chains. However, the traceability of L. monocytogenes in plants during the various seasons has also made it possible to highlight the presence of strains that are specific to egg breaking plants. The study of cleaning and disinfection methods in these plants as well as the recurring bacteria's resistance to disinfectants could provide answers to the egg product industry. Copyright © 2013 Elsevier B.V. All rights reserved.

Investigation of Structure and Property of Indian Cocos nucifera L. Fibre

NASA Astrophysics Data System (ADS)

Basu, Gautam; Mishra, Leena; Samanta, Ashis Kumar

2017-12-01

Structure and physico-mechanical properties of Cocos nucifera L. fibre from a specific agro-climatic region of India, was thoroughly studied. Fine structure of the fibre was examined by Fourier Transform Infra-Red (FTIR) spectroscopy, Thermo-Gravimetric Analysis (TGA), X-Ray Diffraction (XRD), component analysis, Scanning Electron Microscope (SEM) and optical microscope. SEM shows prominent longitudinal cracks and micro-pores on the surface. XRD shows a low degree of crystallinity (45%), bigger crystallite size, and even the presence of appreciable amount of non-cellulose matter. FTIR reveals presence of large quantities of hydroxyl, phenolic and aldehyde groups. Component and thermal analyses indicates presence of cellulose and lignin as major components. Physical parameters reveal that, fibres are highly variable in length (range 44-305 mm), and diameter (range 100-795 µm). Mechanical properties of the fibre viz. breaking tenacity, breaking extensibility, specific work of rupture, and coefficient of friction were measured. Microbial decomposition test under soil reveals excellent durability of coconut fibre which makes it appropriate for the application in geotextiles. Mass specific electrical resistance of 4 Ω-kg/m2 indicates its enhanced insulation as compared to the jute.

Effort-Based Decision-Making in Schizophrenia.

PubMed

Culbreth, Adam J; Moran, Erin K; Barch, Deanna M

2018-08-01

Motivational impairment has long been associated with schizophrenia but the underlying mechanisms are not clearly understood. Recently, a small but growing literature has suggested that aberrant effort-based decision-making may be a potential contributory mechanism for motivational impairments in psychosis. Specifically, multiple reports have consistently demonstrated that individuals with schizophrenia are less willing than healthy controls to expend effort to obtain rewards. Further, this effort-based decision-making deficit has been shown to correlate with severity of negative symptoms and level of functioning, in many but not all studies. In the current review, we summarize this literature and discuss several factors that may underlie aberrant effort-based decision-making in schizophrenia.

Verifying visual properties in sentence verification facilitates picture recognition memory.

PubMed

Pecher, Diane; Zanolie, Kiki; Zeelenberg, René

2007-01-01

According to the perceptual symbols theory (Barsalou, 1999), sensorimotor simulations underlie the representation of concepts. We investigated whether recognition memory for pictures of concepts was facilitated by earlier representation of visual properties of those concepts. During study, concept names (e.g., apple) were presented in a property verification task with a visual property (e.g., shiny) or with a nonvisual property (e.g., tart). Delayed picture recognition memory was better if the concept name had been presented with a visual property than if it had been presented with a nonvisual property. These results indicate that modality-specific simulations are used for concept representation.

Top-down modulation: the crossroads of perception, attention and memory

NASA Astrophysics Data System (ADS)

Gazzaley, Adam

2010-02-01

Research in our laboratory focuses on understanding the neural mechanisms that serve at the crossroads of perception, memory and attention, specifically exploring how brain region interactions underlie these abilities. To accomplish this, we study top-down modulation, the process by which we enhance neural activity associated with relevant information and suppress activity for irrelevant information, thus establishing a neural basis for all higher-order cognitive operations. We also study alterations in top-down modulation that occur with normal aging. Our experiments are performed on human participants, using a multimodal approach that integrates functional MRI (fMRI), transcranial magnetic stimulation (TMS) and electroencephalography (EEG).

Neuropathological Basis of Non-Motor Manifestations of Parkinson’s Disease

PubMed Central

Adler, Charles H.; Beach, Thomas G.

2016-01-01

Non-motor manifestations of Parkinson’s disease (PD) can begin well before motor PD begins. It is now clear, from clinical and autopsy studies, that there is significant Lewy type alpha-synucleinopathy present outside the nigro-striatal pathway, and that this may underlie these non-motor manifestations. This review will discuss neuropathological findings that may underlie non-motor symptoms that either predate motor findings or occur as the disease progresses. PMID:27030013

MENO-II: An AI-Based Programming Tutor.

DTIC Science & Technology

1983-08-01

TUTORing component then attempts to infer the misconception that might underlie the bug and present the student with remedial instruction. We tested the BUG...of the student’s program. The TUTORing component then attempts to inter the misconception that might underlie the bug and present the student with... student errors, MENO-11 can cope with 18 different types of program bugs. These bugs are tied explicitly to a knowledge base of potential misconceptions

Dual-phase evolution in complex adaptive systems

PubMed Central

Paperin, Greg; Green, David G.; Sadedin, Suzanne

2011-01-01

Understanding the origins of complexity is a key challenge in many sciences. Although networks are known to underlie most systems, showing how they contribute to well-known phenomena remains an issue. Here, we show that recurrent phase transitions in network connectivity underlie emergent phenomena in many systems. We identify properties that are typical of systems in different connectivity phases, as well as characteristics commonly associated with the phase transitions. We synthesize these common features into a common framework, which we term dual-phase evolution (DPE). Using this framework, we review the literature from several disciplines to show that recurrent connectivity phase transitions underlie the complex properties of many biological, physical and human systems. We argue that the DPE framework helps to explain many complex phenomena, including perpetual novelty, modularity, scale-free networks and criticality. Our review concludes with a discussion of the way DPE relates to other frameworks, in particular, self-organized criticality and the adaptive cycle. PMID:21247947

Dual-phase evolution in complex adaptive systems.

PubMed

Paperin, Greg; Green, David G; Sadedin, Suzanne

2011-05-06

Understanding the origins of complexity is a key challenge in many sciences. Although networks are known to underlie most systems, showing how they contribute to well-known phenomena remains an issue. Here, we show that recurrent phase transitions in network connectivity underlie emergent phenomena in many systems. We identify properties that are typical of systems in different connectivity phases, as well as characteristics commonly associated with the phase transitions. We synthesize these common features into a common framework, which we term dual-phase evolution (DPE). Using this framework, we review the literature from several disciplines to show that recurrent connectivity phase transitions underlie the complex properties of many biological, physical and human systems. We argue that the DPE framework helps to explain many complex phenomena, including perpetual novelty, modularity, scale-free networks and criticality. Our review concludes with a discussion of the way DPE relates to other frameworks, in particular, self-organized criticality and the adaptive cycle.

Autism and 15q11-q13 disorders: behavioral, genetic, and pathophysiological issues.

PubMed

Dykens, Elisabeth M; Sutcliffe, James S; Levitt, Pat

2004-01-01

New insights into biological factors that underlie autism may be gained by comparing autism to other neurodevelopmental disorders that have autistic features and relatively well-delineated genetic etiologies or neurobiological findings. This review moves beyond global diagnoses of autism and instead uses an endophenotypic approach to compare specific clusters of autistic symptomatology to features of chromosome 15q11-q13 disorders. Paternally or maternally derived deficiencies of 15q11-q13 result in Prader-Willi or Angelman syndromes, and we first use a global approach to review potential autism susceptibility genes in the 15q11-q13 region. We then use a more trait-based approach to suggest possible ties between specific phenotypic characteristics of autism and Prader-Willi syndrome, namely savant-like skills. We conclude with insights from pathophysiological studies that implicate altered development of specific neuron types and circuits in the cerebral cortex as part of the pathophysiological processes associated with autism and mental retardation. Copyright 2004 Wiley-Liss, Inc.

Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio.

PubMed

Weidmann, Chase A; Qiu, Chen; Arvola, René M; Lou, Tzu-Fang; Killingsworth, Jordan; Campbell, Zachary T; Tanaka Hall, Traci M; Goldstrohm, Aaron C

2016-08-02

Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAs that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.

Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weidmann, Chase A.; Qiu, Chen; Arvola, René M.

Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation byDrosophilaPumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAs that aremore » not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulatedin vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.« less

Fiber type-specific afferent nerve activity induced by transient contractions of rat bladder smooth muscle in pathological states

PubMed Central

Kuga, Nahoko; Tanioka, Asao; Hagihara, Koichiro; Kawai, Tomoyuki

2017-01-01

Bladder smooth muscle shows spontaneous phasic contractions, which undergo a variety of abnormal changes depending on pathological conditions. How abnormal contractions affect the activity of bladder afferent nerves remains to be fully tested. In this study, we examined the relationship between transient increases in bladder pressure, representing transient contraction of bladder smooth muscle, and spiking patterns of bladder afferent fibers of the L6 dorsal root, in rat pathological models. All recordings were performed at a bladder pressure of approximately 10 cmH2O by maintaining the degree of bladder filling. In the cyclophosphamide-induced model, both Aδ and C fibers showed increased sensitivity to transient bladder pressure increases. In the prostaglandin E2-induced model, Aδ fibers, but not C fibers, specifically showed overexcitation that was time-locked with transient bladder pressure increases. These fiber type-specific changes in nerve spike patterns may underlie the symptoms of urinary bladder diseases. PMID:29267380

77 FR 2342 - Fifth Meeting: RTCA, Next Gen Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-17

... University, Florida NextGen Test Bed, 557 Innovation Way, Daytona Beach, FL 32114. FOR FURTHER INFORMATION... Capabilities to Identified Metroplexes--a recommendation derived from a mapping of integrated capabilities to... specific capabilities. Lunch Break Review and Approve Recommendations for Submission to FAA DataComm...

Improving TCP Performance over Mobile Satellite Channels: The ACKPrime Approach

NASA Technical Reports Server (NTRS)

Scott, Keith; Czetty, Stephen

1998-01-01

Various issues associated with "Improving TCP Performance over Mobile Satellite Channels: The ACKPrime Approach" are presented in viewgraph form. Specific topics include: 1) TCP over mobile satellite links; 2) ways of breaking the control loop at the groundstation; 3) ACK implementation; and 4) ACK performance.

In vitro assembly of semi-artificial molecular machine and its use for detection of DNA damage.

PubMed

Minchew, Candace L; Didenko, Vladimir V

2012-01-11

Naturally occurring bio-molecular machines work in every living cell and display a variety of designs. Yet the development of artificial molecular machines centers on devices capable of directional motion, i.e. molecular motors, and on their scaled-down mechanical parts (wheels, axels, pendants etc). This imitates the macro-machines, even though the physical properties essential for these devices, such as inertia and momentum conservation, are not usable in the nanoworld environments. Alternative designs, which do not follow the mechanical macromachines schemes and use mechanisms developed in the evolution of biological molecules, can take advantage of the specific conditions of the nanoworld. Besides, adapting actual biological molecules for the purposes of nano-design reduces potential dangers the nanotechnology products may pose. Here we demonstrate the assembly and application of one such bio-enabled construct, a semi-artificial molecular device which combines a naturally-occurring molecular machine with artificial components. From the enzymology point of view, our construct is a designer fluorescent enzyme-substrate complex put together to perform a specific useful function. This assembly is by definition a molecular machine, as it contains one. Yet, its integration with the engineered part - fluorescent dual hairpin - re-directs it to a new task of labeling DNA damage. Our construct assembles out of a 32-mer DNA and an enzyme vaccinia topoisomerase I (VACC TOPO). The machine then uses its own material to fabricate two fluorescently labeled detector units (Figure 1). One of the units (green fluorescence) carries VACC TOPO covalently attached to its 3'end and another unit (red fluorescence) is a free hairpin with a terminal 3'OH. The units are short-lived and quickly reassemble back into the original construct, which subsequently recleaves. In the absence of DNA breaks these two units continuously separate and religate in a cyclic manner. In tissue sections with DNA damage, the topoisomerase-carrying detector unit selectively attaches to blunt-ended DNA breaks with 5'OH (DNase II-type breaks), fluorescently labeling them. The second, enzyme-free hairpin formed after oligonucleotide cleavage, will ligate to a 5'PO(4) blunt-ended break (DNase I-type breaks), if T4 DNA ligase is present in the solution. When T4 DNA ligase is added to a tissue section or a solution containing DNA with 5'PO(4) blunt-ended breaks, the ligase reacts with 5'PO(4) DNA ends, forming semi-stable enzyme-DNA complexes. The blunt ended hairpins will interact with these complexes releasing ligase and covalently linking hairpins to DNA, thus labeling 5'PO(4) blunt-ended DNA breaks. This development exemplifies a new practical approach to the design of molecular machines and provides a useful sensor for detection of apoptosis and DNA damage in fixed cells and tissues. Copyright © 2012 Journal of Visualized Experiments

Investigating the impact of surface wave breaking on modeling the trajectories of drifters in the northern Adriatic Sea during a wind-storm event

USGS Publications Warehouse

Carniel, S.; Warner, J.C.; Chiggiato, J.; Sclavo, M.

2009-01-01

An accurate numerical prediction of the oceanic upper layer velocity is a demanding requirement for many applications at sea and is a function of several near-surface processes that need to be incorporated in a numerical model. Among them, we assess the effects of vertical resolution, different vertical mixing parameterization (the so-called Generic Length Scale -GLS- set of k-??, k-??, gen, and the Mellor-Yamada), and surface roughness values on turbulent kinetic energy (k) injection from breaking waves. First, we modified the GLS turbulence closure formulation in the Regional Ocean Modeling System (ROMS) to incorporate the surface flux of turbulent kinetic energy due to wave breaking. Then, we applied the model to idealized test cases, exploring the sensitivity to the above mentioned factors. Last, the model was applied to a realistic situation in the Adriatic Sea driven by numerical meteorological forcings and river discharges. In this case, numerical drifters were released during an intense episode of Bora winds that occurred in mid-February 2003, and their trajectories compared to the displacement of satellite-tracked drifters deployed during the ADRIA02-03 sea-truth campaign. Results indicted that the inclusion of the wave breaking process helps improve the accuracy of the numerical simulations, subject to an increase in the typical value of the surface roughness z0. Specifically, the best performance was obtained using ??CH = 56,000 in the Charnok formula, the wave breaking parameterization activated, k-?? as the turbulence closure model. With these options, the relative error with respect to the average distance of the drifter was about 25% (5.5 km/day). The most sensitive factors in the model were found to be the value of ??CH enhanced with respect to a standard value, followed by the adoption of wave breaking parameterization and the particular turbulence closure model selected. ?? 2009 Elsevier Ltd.

ERK Signaling in the Pituitary Is Required for Female But Not Male Fertility

PubMed Central

Bliss, Stuart P.; Miller, Andrew; Navratil, Amy M.; Xie, JianJun; McDonough, Sean P.; Fisher, Patricia J.; Landreth, Gary E.; Roberson, Mark S.

2009-01-01

Males and females require different patterns of pituitary gonadotropin secretion for fertility. The mechanisms underlying these gender-specific profiles of pituitary hormone production are unknown; however, they are fundamental to understanding the sexually dimorphic control of reproductive function at the molecular level. Several studies suggest that ERK1 and -2 are essential modulators of hypothalamic GnRH-mediated regulation of pituitary gonadotropin production and fertility. To test this hypothesis, we generated mice with a pituitary-specific depletion of ERK1 and 2 and examined a range of physiological parameters including fertility. We find that ERK signaling is required in females for ovulation and fertility, whereas male reproductive function is unaffected by this signaling deficiency. The effects of ERK pathway ablation on LH biosynthesis underlie this gender-specific phenotype, and the molecular mechanism involves a requirement for ERK-dependent up-regulation of the transcription factor Egr1, which is necessary for LHβ expression. Together, these findings represent a significant advance in elucidating the molecular basis of gender-specific regulation of the hypothalamic-pituitary-gonadal axis and sexually dimorphic control of fertility. PMID:19372235

Hepatitis E virus and fulminant hepatitis--a virus or host-specific pathology?

PubMed

Smith, Donald B; Simmonds, Peter

2015-04-01

Fulminant hepatitis is a rare outcome of infection with hepatitis E virus. Several recent reports suggest that virus variation is an important determinant of disease progression. To critically examine the evidence that virus-specific factors underlie the development of fulminant hepatitis following hepatitis E virus infection. Published sequence information of hepatitis E virus isolates from patients with and without fulminant hepatitis was collected and analysed using statistical tests to identify associations between virus polymorphisms and disease outcome. Fulminant hepatitis has been reported following infection with all four hepatitis E virus genotypes that infect humans comprising multiple phylogenetic lineages within genotypes 1, 3 and 4. Analysis of virus sequences from individuals infected by a common source did not detect any common substitutions associated with progression to fulminant hepatitis. Re-analysis of previously reported associations between virus substitutions and fulminant hepatitis suggests that these were probably the result of sampling biases. Host-specific factors rather than virus genotype, variants or specific substitutions appear to be responsible for the development of fulminant hepatitis. © 2014 The Authors. Liver International Published by John Wiley & Sons Ltd.

Habitat-Specific Morphological Variation among Threespine Sticklebacks (Gasterosteus aculeatus) within a Drainage Basin

PubMed Central

Webster, Mike M.; Atton, Nicola; Hart, Paul J. B.; Ward, Ashley J. W.

2011-01-01

Habitat-specific morphological variation, often corresponding to resource specialization, is well documented in freshwater fishes. In this study we used landmark based morphometric analyses to investigate morphological variation among threespine sticklebacks (Gasterosteus aculeatus L.) from four interconnected habitat types within a single lowland drainage basin in eastern England. These included the upper and lower reaches of the river, the estuary, a connected ditch network and a coastal salt marsh. We found significant habitat-specific differences in morphology, with three axes of variation describing differences in orbit diameter, body depth, caudal peduncle shape and pectoral fin positioning as well as variation in relative dorsal and pelvic spine size. Interestingly, the ditch system, an artificial and heavily managed habitat, is populated by sticklebacks with a characteristic morphology, suggesting that human management of habitats can in some circumstances lead to morphological variation among the animals that inhabit them. We discuss the mechanisms that conceivably underlie the observed morphological variation and the further work necessary to identify them. Finally, we consider the implications of habitat-specific body shape variation for the behavioural ecology of this ecologically generalist species. PMID:21698269

Ethics skills laboratory experience for surgery interns.

PubMed

Moon, Margaret R; Hughes, Mark T; Chen, Jiin-Yu; Khaira, Kiran; Lipsett, Pamela; Carrese, Joseph A

2014-01-01

Ethics curricula are nearly universal in residency training programs, but the content and delivery methods are not well described, and there is still a relative paucity of literature evaluating the effect of ethics curricula. Several commentators have called for more ethics curriculum development at the postgraduate level, and specifically in surgery training. We detail our development and implementation of a clinical ethics curriculum for surgery interns. We developed curricula and simulated patient cases for 2 core clinical ethics skills--breaking bad news and obtaining informed consent. Educational sessions for each topic included (1) framework development (discussion of interns' current experience, development of a consensus framework for ethical practice, and comparison with established frameworks) and (2) practice with simulated patient followed by peer and faculty feedback. At the beginning and end of each session, we administered a test of confidence and knowledge about the topics to assess the effect of the sessions. A total of 98 surgical interns participated in the ethics skills laboratory from Spring 2008 to Spring 2011. We identified significant improvement in confidence regarding the appropriate content of informed consent (<0.001) and capacity to break bad news (<0.001). We also identified significant improvement in overall knowledge regarding informed consent (<0.01), capacity assessment (<0.05), and breaking bad news (0.001). Regarding specific components of informed consent, capacity assessment, and breaking bad news, significant improvement was shown in some areas, while we failed to improve knowledge in others. Through faculty-facilitated small group discussion, surgery interns were able to develop frameworks for ethical practice that paralleled established frameworks. Skills-based training in clinical ethics resulted in an increase in knowledge scores and self-reported confidence. Evaluation of 4 annual cohorts of surgery interns demonstrates significant successes and some areas for improvement in this educational intervention. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

A Clinical Study of Subtype-based Prevalence of Dry Eye.

PubMed

Rege, Aditya; Kulkarni, Varsha; Puthran, Neelam; Khandgave, Tejaswini

2013-10-01

Dry Eye is a multifactorial disease of the tearfilm and the ocular surface which may be due to reduced tear production or excessive tear evaporation resulting in discomfort, visual disturbance, and tear film instability with a potential damage to the ocular surface. Various population-based studies have been done to find out the prevalence and the magnitude of the problem. Women Health Study reported prevalence of 7.8% after screening 36995 subjects above 49 years by interview. The prevalence reported by Blue Mountain Study was 15.3% .The Beaver Dam Study and Shiphai Eye studies are other studies reporting prevalence of 14.5% and 33.7% respectively. McMonnies questionnaire is a widely used screening instrument for Dry-Eye syndromes with sensitivity reportedly varying between 87% and 98% and specificity between 87% and 97%. Prevalence studies use McMonnie's questionnaire for screening individuals for Dry Eye, whereafter tests like Schirmer's test, Tear Film Break Up Time test, Rose Bengal test, Lissamine Green test and Meibomian Gland Dysfunction test are useful for further evaluation. While these tests help to differentiate the subtypes of Dry Eye such as Lipid Anomaly Dry Eye, Aqueous Tear Deficiency and Mucin Layer Deficiency, however, their sensitivity and specificity has not been widely studied. Additionally, very few studies have reported the prevalence of the various subtypes of Dry Eye. To determine the subtype-based prevalence of Dry Eye, to study the specificity and sensitivity of clinical tests for Dry Eye and to correlate McMonnies questionnaire with Dry Eye tests results. A prospective, cross-sectional, observational study, duly approved by the Institutional Ethics Committee, was conducted from October 2010 to April 2012. A total of 4750 subjects above 18 yrs of age were screened by the McMonnies questionnaire. Respondents having a score greater than 14.5 were subjected to clinical Dry Eye tests. The data obtained was analyzed using chi-square test. p value < 0.005 was considered statistically significant.The specificity and sensitivity of each clinical test was calculated using Schirmer's test as gold standard. The prevalence of Dry Eye was 15.4%, with a female preponderance (p = 0.01) and a significant increase with age above 60 years was noted (p<0.0001). Tear Film Break Up Time was the most reliable test with a good sensitivity (68.85%) and specificity (78.32%). Lipid Anomaly Dry Eye was the most prevalent (14.48%) followed by Aqueous Tear Deficiency (13.36%) and Mucin Layer Deficiency (3.51%). A positive correlation between McMonnies score and severity of Dry Eye was seen. This study suggests that Lipid Layer Anomaly is the most prevalent subtype in Dry Eye. Tear Film Break Up Time test is the most likely test to diagnose mild Dry Eye. McMonies Questionnaire can be effectively used for screening of a large population. Tear Film Break Up Time was found to have better sensitivity as well as specificity than other tests used for diagnosing Dry Eye.

The minimal SUSY B - L model: simultaneous Wilson lines and string thresholds

DOE PAGES

Deen, Rehan; Ovrut, Burt A.; Purves, Austin

2016-07-08

In previous work, we presented a statistical scan over the soft supersymmetry breaking parameters of the minimal SUSY B - L model. For specificity of calculation, unification of the gauge parameters was enforced by allowing the two Z 3×Z 3 Wilson lines to have mass scales separated by approximately an order of magnitude. This introduced an additional “left-right” sector below the unification scale. In this paper, for three important reasons, we modify our previous analysis by demanding that the mass scales of the two Wilson lines be simultaneous and equal to an “average unification” mass U >. The present analysismore » is 1) more “natural” than the previous calculations, which were only valid in a very specific region of the Calabi-Yau moduli space, 2) the theory is conceptually simpler in that the left-right sector has been removed and 3) in the present analysis the lack of gauge unification is due to threshold effects — particularly heavy string thresholds, which we calculate statistically in detail. As in our previous work, the theory is renormalization group evolved from U > to the electroweak scale — being subjected, sequentially, to the requirement of radiative B - L and electroweak symmetry breaking, the present experimental lower bounds on the B - L vector boson and sparticle masses, as well as the lightest neutral Higgs mass of ~125 GeV. The subspace of soft supersymmetry breaking masses that satisfies all such constraints is presented and shown to be substantial.« less

Two-stage perceptual learning to break visual crowding.

PubMed

Zhu, Ziyun; Fan, Zhenzhi; Fang, Fang

2016-01-01

When a target is presented with nearby flankers in the peripheral visual field, it becomes harder to identify, which is referred to as crowding. Crowding sets a fundamental limit of object recognition in peripheral vision, preventing us from fully appreciating cluttered visual scenes. We trained adult human subjects on a crowded orientation discrimination task and investigated whether crowding could be completely eliminated by training. We discovered a two-stage learning process with this training task. In the early stage, when the target and flankers were separated beyond a certain distance, subjects acquired a relatively general ability to break crowding, as evidenced by the fact that the breaking of crowding could transfer to another crowded orientation, even a crowded motion stimulus, although the transfer to the opposite visual hemi-field was weak. In the late stage, like many classical perceptual learning effects, subjects' performance gradually improved and showed specificity to the trained orientation. We also found that, when the target and flankers were spaced too finely, training could only reduce, rather than completely eliminate, the crowding effect. This two-stage learning process illustrates a learning strategy for our brain to deal with the notoriously difficult problem of identifying peripheral objects in clutter. The brain first learned to solve the "easy and general" part of the problem (i.e., improving the processing resolution and segmenting the target and flankers) and then tackle the "difficult and specific" part (i.e., refining the representation of the target).

Myosin Heads Are Displaced from Actin Filaments in the In Situ Beating Rat Heart in Early Diabetes

PubMed Central

Jenkins, Mathew J.; Pearson, James T.; Schwenke, Daryl O.; Edgley, Amanda J.; Sonobe, Takashi; Fujii, Yutaka; Ishibashi-Ueda, Hatsue; Kelly, Darren J.; Yagi, Naoto; Shirai, Mikiyasu

2013-01-01

Diabetes is independently associated with a specific cardiomyopathy, characterized by impaired cardiac muscle relaxation and force development. Using synchrotron radiation small-angle x-ray scattering, this study investigated in the in situ heart and in real-time whether changes in cross-bridge disposition and myosin interfilament spacing underlie the early development of diabetic cardiomyopathy. Experiments were conducted using anesthetized Sprague-Dawley rats 3 weeks after treatment with either vehicle (control) or streptozotocin (diabetic). Diffraction patterns were recorded during baseline and dobutamine infusions simultaneous with ventricular pressure-volumetry. From these diffraction patterns myosin mass transfer to actin filaments was assessed as the change in intensity ratio (I1,0/I1,1). In diabetic hearts cross-bridge disposition was most notably abnormal in the diastolic phase (p < 0.05) and to a lesser extent the systolic phase (p < 0.05). In diabetic rats only, there was a transmural gradient of contractile depression. Elevated diabetic end-diastolic intensity ratios were correlated with the suppression of diastolic function (p < 0.05). Furthermore, the expected increase in myosin head transfer by dobutamine was significantly blunted in diabetic animals (p < 0.05). Interfilament spacing did not differ between groups. We reveal that impaired cross-bridge disposition and radial transfer may thus underlie the early decline in ventricular function observed in diabetic cardiomyopathy. PMID:23473489

Genome-wide analysis of genetic susceptibility to language impairment in an isolated Chilean population

PubMed Central

Villanueva, Pia; Newbury, Dianne F; Jara, Lilian; De Barbieri, Zulema; Mirza, Ghazala; Palomino, Hernán M; Fernández, María Angélica; Cazier, Jean-Baptiste; Monaco, Anthony P; Palomino, Hernán

2011-01-01

Specific language impairment (SLI) is an unexpected deficit in the acquisition of language skills and affects between 5 and 8% of pre-school children. Despite its prevalence and high heritability, our understanding of the aetiology of this disorder is only emerging. In this paper, we apply genome-wide techniques to investigate an isolated Chilean population who exhibit an increased frequency of SLI. Loss of heterozygosity (LOH) mapping and parametric and non-parametric linkage analyses indicate that complex genetic factors are likely to underlie susceptibility to SLI in this population. Across all analyses performed, the most consistently implicated locus was on chromosome 7q. This locus achieved highly significant linkage under all three non-parametric models (max NPL=6.73, P=4.0 × 10−11). In addition, it yielded a HLOD of 1.24 in the recessive parametric linkage analyses and contained a segment that was homozygous in two affected individuals. Further, investigation of this region identified a two-SNP haplotype that occurs at an increased frequency in language-impaired individuals (P=0.008). We hypothesise that the linkage regions identified here, in particular that on chromosome 7, may contain variants that underlie the high prevalence of SLI observed in this isolated population and may be of relevance to other populations affected by language impairments. PMID:21248734

Sleep interacts with aβ to modulate intrinsic neuronal excitability.

PubMed

Tabuchi, Masashi; Lone, Shahnaz R; Liu, Sha; Liu, Qili; Zhang, Julia; Spira, Adam P; Wu, Mark N

2015-03-16

Emerging data suggest an important relationship between sleep and Alzheimer's disease (AD), but how poor sleep promotes the development of AD remains unclear. Here, using a Drosophila model of AD, we provide evidence suggesting that changes in neuronal excitability underlie the effects of sleep loss on AD pathogenesis. β-amyloid (Aβ) accumulation leads to reduced and fragmented sleep, while chronic sleep deprivation increases Aβ burden. Moreover, enhancing sleep reduces Aβ deposition. Increasing neuronal excitability phenocopies the effects of reducing sleep on Aβ, and decreasing neuronal activity blocks the elevated Aβ accumulation induced by sleep deprivation. At the single neuron level, we find that chronic sleep deprivation, as well as Aβ expression, enhances intrinsic neuronal excitability. Importantly, these data reveal that sleep loss exacerbates Aβ-induced hyperexcitability and suggest that defects in specific K(+) currents underlie the hyperexcitability caused by sleep loss and Aβ expression. Finally, we show that feeding levetiracetam, an anti-epileptic medication, to Aβ-expressing flies suppresses neuronal excitability and significantly prolongs their lifespan. Our findings directly link sleep loss to changes in neuronal excitability and Aβ accumulation and further suggest that neuronal hyperexcitability is an important mediator of Aβ toxicity. Taken together, these data provide a mechanistic framework for a positive feedback loop, whereby sleep loss and neuronal excitation accelerate the accumulation of Aβ, a key pathogenic step in the development of AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sleep Interacts with Aβ to Modulate Intrinsic Neuronal Excitability

PubMed Central

Tabuchi, Masashi; Lone, Shahnaz R.; Liu, Sha; Liu, Qili; Zhang, Julia; Spira, Adam P.; Wu, Mark N.

2015-01-01

SUMMARY Background Emerging data suggest an important relationship between sleep and Alzheimer’s Disease (AD), but how poor sleep promotes the development of AD remains unclear. Results Here, using a Drosophila model of AD, we provide evidence suggesting that changes in neuronal excitability underlie the effects of sleep loss on AD pathogenesis. β-amyloid (Aβ) accumulation leads to reduced and fragmented sleep, while chronic sleep deprivation increases Aβ burden. Moreover, enhancing sleep reduces Aβ deposition. Increasing neuronal excitability phenocopies the effects of reducing sleep on Aβ, and decreasing neuronal activity blocks the elevated Aβ accumulation induced by sleep deprivation. At the single neuron level, we find that chronic sleep deprivation, as well as Aβ expression, enhances intrinsic neuronal excitability. Importantly, these data reveal that sleep loss exacerbates Aβ–induced hyperexcitability and suggest that defects in specific K+ currents underlie the hyperexcitability caused by sleep loss and Aβ expression. Finally, we show that feeding levetiracetam, an anti-epileptic medication, to Aβ-expressing flies suppresses neuronal excitability and significantly prolongs their lifespan. Conclusions Our findings directly link sleep loss to changes in neuronal excitability and Aβ accumulation and further suggest that neuronal hyperexcitability is an important mediator of Aβ toxicity. Taken together, these data provide a mechanistic framework for a positive feedback loop, whereby sleep loss and neuronal excitation accelerate the accumulation of Aβ, a key pathogenic step in the development of AD. PMID:25754641

The evolution of mollusc shells.

PubMed

McDougall, Carmel; Degnan, Bernard M

2018-05-01

Molluscan shells are externally fabricated by specialized epithelial cells on the dorsal mantle. Although a conserved set of regulatory genes appears to underlie specification of mantle progenitor cells, the genes that contribute to the formation of the mature shell are incredibly diverse. Recent comparative analyses of mantle transcriptomes and shell proteomes of gastropods and bivalves are consistent with shell diversity being underpinned by a rapidly evolving mantle secretome (suite of genes expressed in the mantle that encode secreted proteins) that is the product of (a) high rates of gene co-option into and loss from the mantle gene regulatory network, and (b) the rapid evolution of coding sequences, particular those encoding repetitive low complexity domains. Outside a few conserved genes, such as carbonic anhydrase, a so-called "biomineralization toolkit" has yet to be discovered. Despite this, a common suite of protein domains, which are often associated with the extracellular matrix and immunity, appear to have been independently and often uniquely co-opted into the mantle secretomes of different species. The evolvability of the mantle secretome provides a molecular explanation for the evolution and diversity of molluscan shells. These genomic processes are likely to underlie the evolution of other animal biominerals, including coral and echinoderm skeletons. This article is categorized under: Comparative Development and Evolution > Regulation of Organ Diversity Comparative Development and Evolution > Evolutionary Novelties. © 2018 Wiley Periodicals, Inc.

Uncovering the requirements of cognitive work.

PubMed

Roth, Emilie M

2008-06-01

In this article, the author provides an overview of cognitive analysis methods and how they can be used to inform system analysis and design. Human factors has seen a shift toward modeling and support of cognitively intensive work (e.g., military command and control, medical planning and decision making, supervisory control of automated systems). Cognitive task analysis and cognitive work analysis methods extend traditional task analysis techniques to uncover the knowledge and thought processes that underlie performance in cognitively complex settings. The author reviews the multidisciplinary roots of cognitive analysis and the variety of cognitive task analysis and cognitive work analysis methods that have emerged. Cognitive analysis methods have been used successfully to guide system design, as well as development of function allocation, team structure, and training, so as to enhance performance and reduce the potential for error. A comprehensive characterization of cognitive work requires two mutually informing analyses: (a) examination of domain characteristics and constraints that define cognitive requirements and challenges and (b) examination of practitioner knowledge and strategies that underlie both expert and error-vulnerable performance. A variety of specific methods can be adapted to achieve these aims within the pragmatic constraints of particular projects. Cognitive analysis methods can be used effectively to anticipate cognitive performance problems and specify ways to improve individual and team cognitive performance (be it through new forms of training, user interfaces, or decision aids).

Testing the effects of adolescent alcohol use on adult conflict-related theta dynamics.

PubMed

Harper, Jeremy; Malone, Stephen M; Iacono, William G

2017-11-01

Adolescent alcohol use (AAU) is associated with brain anomalies, but less is known about long-term neurocognitive effects. Despite theoretical models linking AAU to diminished cognitive control, empirical work testing this relationship with specific cognitive control neural correlates (e.g., prefrontal theta-band EEG dynamics) remains scarce. A longitudinal twin design was used to test the hypothesis that greater AAU is associated with reduced conflict-related EEG theta-band dynamics in adulthood, and to examine the genetic/environmental etiology of this association. In a large (N=718) population-based prospective twin sample, AAU was assessed at ages 11/14/17. Twins completed a flanker task at age 29 to elicit EEG theta-band medial frontal cortex (MFC) power and medial-dorsal prefrontal cortex (MFC-dPFC) connectivity. Two complementary analytic methods (cotwin control analysis; biometric modeling) were used to disentangle the genetic/shared environmental risk towards AAU from possible alcohol exposure effects on theta dynamics. AAU was negatively associated with adult cognitive control-related theta-band MFC power and MFC-dPFC functional connectivity. Genetic influences primarily underlie these associations. Findings provide strong evidence that genetic factors underlie the comorbidity between AAU and diminished cognitive control-related theta dynamics in adulthood. Conflict-related theta-band dynamics appear to be candidate brain-based endophenotypes/mechanisms for AAU. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Enamel protein regulation and dental and periodontal physiopathology in MSX2 mutant mice.

PubMed

Molla, Muriel; Descroix, Vianney; Aïoub, Muhanad; Simon, Stéphane; Castañeda, Beatriz; Hotton, Dominique; Bolaños, Alba; Simon, Yohann; Lezot, Frédéric; Goubin, Gérard; Berdal, Ariane

2010-11-01

Signaling pathways that underlie postnatal dental and periodontal physiopathology are less studied than those of early tooth development. Members of the muscle segment homeobox gene (Msx) family encode homeoproteins that show functional redundancy during development and are known to be involved in epithelial-mesenchymal interactions that lead to crown morphogenesis and ameloblast cell differentiation. This study analyzed the MSX2 protein during mouse postnatal growth as well as in the adult. The analysis focused on enamel and periodontal defects and enamel proteins in Msx2-null mutant mice. In the epithelial lifecycle, the levels of MSX2 expression and enamel protein secretion were inversely related. Msx2+/- mice showed increased amelogenin expression, enamel thickness, and rod size. Msx2-/- mice displayed compound phenotypic characteristics of enamel defects, related to both enamel-specific gene mutations (amelogenin and enamelin) in isolated amelogenesis imperfecta, and cell-cell junction elements (laminin 5 and cytokeratin 5) in other syndromes. These effects were also related to ameloblast disappearance, which differed between incisors and molars. In Msx2-/- roots, Malassez cells formed giant islands that overexpressed amelogenin and ameloblastin that grew over months. Aberrant expression of enamel proteins is proposed to underlie the regional osteopetrosis and hyperproduction of cellular cementum. These enamel and periodontal phenotypes of Msx2 mutants constitute the first case report of structural and signaling defects associated with enamel protein overexpression in a postnatal context.

Memory and reward systems coproduce 'nostalgic' experiences in the brain.

PubMed

Oba, Kentaro; Noriuchi, Madoka; Atomi, Tomoaki; Moriguchi, Yoshiya; Kikuchi, Yoshiaki

2016-07-01

People sometimes experience an emotional state known as 'nostalgia', which involves experiencing predominantly positive emotions while remembering autobiographical events. Nostalgia is thought to play an important role in psychological resilience. Previous neuroimaging studies have shown involvement of memory and reward systems in such experiences. However, it remains unclear how these two systems are collaboratively involved with nostalgia experiences. Here, we conducted a functional magnetic resonance imaging study of healthy females to investigate the relationship between memory-reward co-activation and nostalgia, using childhood-related visual stimuli. Moreover, we examined the factors constituting nostalgia and their neural correlates. We confirmed the presence of nostalgia-related activity in both memory and reward systems, including the hippocampus (HPC), substantia nigra/ventral tegmental area (SN/VTA), and ventral striatum (VS). We also found significant HPC-VS co-activation, with its strength correlating with individual 'nostalgia tendencies'. Factor analyses showed that two dimensions underlie nostalgia: emotional and personal significance and chronological remoteness, with the former correlating with caudal SN/VTA and left anterior HPC activity, and the latter correlating with rostral SN/VTA activity. These findings demonstrate the cooperative activity of memory and reward systems, where each system has a specific role in the construction of the factors that underlie the experience of nostalgia. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Neuromolecular responses to social challenge: common mechanisms across mouse, stickleback fish, and honey bee.

PubMed

Rittschof, Clare C; Bukhari, Syed Abbas; Sloofman, Laura G; Troy, Joseph M; Caetano-Anollés, Derek; Cash-Ahmed, Amy; Kent, Molly; Lu, Xiaochen; Sanogo, Yibayiri O; Weisner, Patricia A; Zhang, Huimin; Bell, Alison M; Ma, Jian; Sinha, Saurabh; Robinson, Gene E; Stubbs, Lisa

2014-12-16

Certain complex phenotypes appear repeatedly across diverse species due to processes of evolutionary conservation and convergence. In some contexts like developmental body patterning, there is increased appreciation that common molecular mechanisms underlie common phenotypes; these molecular mechanisms include highly conserved genes and networks that may be modified by lineage-specific mutations. However, the existence of deeply conserved mechanisms for social behaviors has not yet been demonstrated. We used a comparative genomics approach to determine whether shared neuromolecular mechanisms could underlie behavioral response to territory intrusion across species spanning a broad phylogenetic range: house mouse (Mus musculus), stickleback fish (Gasterosteus aculeatus), and honey bee (Apis mellifera). Territory intrusion modulated similar brain functional processes in each species, including those associated with hormone-mediated signal transduction and neurodevelopment. Changes in chromosome organization and energy metabolism appear to be core, conserved processes involved in the response to territory intrusion. We also found that several homologous transcription factors that are typically associated with neural development were modulated across all three species, suggesting that shared neuronal effects may involve transcriptional cascades of evolutionarily conserved genes. Furthermore, immunohistochemical analyses of a subset of these transcription factors in mouse again implicated modulation of energy metabolism in the behavioral response. These results provide support for conserved genetic "toolkits" that are used in independent evolutions of the response to social challenge in diverse taxa.

Geologic map of the Valdez D-1 and D-2 quadrangles (Mount Wrangell Volcano), Alaska

USGS Publications Warehouse

Richter, D.H.; McGimsey, R.G.; Labay, Keith A.; Lanphere, M.A.; Moore, R.B.; Nye, C.J.; Rosenkrans, D.S.; Winkler, G.R.

2016-04-29

This study was directed toward Mount Wrangell volcano and the older Wrangell volcanic field rocks that underlie the volcano. These older lavas include the Chetaslina lavas (867 ka–1,650 ka) and a basaltic andesite–dacite center (1,590 ka–1,640 ka) whose source areas are not well defined. Older Paleozoic and Mesozoic sedimentary, igneous, and metamorphic rocks of the Wrangellia terrane underlie the entire Wrangell volcanic field.

Toughening elastomers with sacrificial bonds and watching them break

NASA Astrophysics Data System (ADS)

Creton, Costantino

2014-03-01

Most unfilled elastomers are relatively brittle, in particular when the average molecular weight between crosslinks is lower than the average molecular weight between entanglements. We created a new class of tough elastomers by introducing isotropically prestretched chains inside ordinary acrylic elastomers by successive swelling and polymerization steps. These new materials combine a high entanglement density with a densely crosslinked structure reaching elastic moduli of 4 MPa and fracture strength of 25 MPa. The highly prestretched chains are the minority in the material and can break in the bulk of the material before catastrophic failure occurs, increasing the toughness of the material by two orders of magnitude up to 5 kJ/m2. To investigate the details of the toughening mechanism we introduced specific sacrificial dioxetane bonds in the prestretched chains that emit light when they break. In uniaxial extension cyclic experiments, we checked that the light emission corresponded exactly and quantitatively to the energy dissipation in each cycle demonstrating that short chains break first and long chains later. We then watched crack propagation in notched samples and mapped spatially the location of bond breakage ahead of the crack tip before and during propagation. This new toughening mechanism for elastomers creates superentangled rubbers and is ideally suited to overcome the trade-off between toughness and stiffness of ordinary elastomers. We gratefully acknowledge funding from DSM Ahead

Kinematic dynamo, supersymmetry breaking, and chaos

NASA Astrophysics Data System (ADS)

Ovchinnikov, Igor V.; Enßlin, Torsten A.

2016-04-01

The kinematic dynamo (KD) describes the growth of magnetic fields generated by the flow of a conducting medium in the limit of vanishing backaction of the fields onto the flow. The KD is therefore an important model system for understanding astrophysical magnetism. Here, the mathematical correspondence between the KD and a specific stochastic differential equation (SDE) viewed from the perspective of the supersymmetric theory of stochastics (STS) is discussed. The STS is a novel, approximation-free framework to investigate SDEs. The correspondence reported here permits insights from the STS to be applied to the theory of KD and vice versa. It was previously known that the fast KD in the idealistic limit of no magnetic diffusion requires chaotic flows. The KD-STS correspondence shows that this is also true for the diffusive KD. From the STS perspective, the KD possesses a topological supersymmetry, and the dynamo effect can be viewed as its spontaneous breakdown. This supersymmetry breaking can be regarded as the stochastic generalization of the concept of dynamical chaos. As this supersymmetry breaking happens in both the diffusive and the nondiffusive cases, the necessity of the underlying SDE being chaotic is given in either case. The observed exponentially growing and oscillating KD modes prove physically that dynamical spectra of the STS evolution operator that break the topological supersymmetry exist with both real and complex ground state eigenvalues. Finally, we comment on the nonexistence of dynamos for scalar quantities.

The highest-ranking rooster has priority to announce the break of dawn.

PubMed

Shimmura, Tsuyoshi; Ohashi, Shosei; Yoshimura, Takashi

2015-07-23

The "cock-a-doodle-doo" crowing of roosters, which symbolizes the break of dawn in many cultures, is controlled by the circadian clock. When one rooster announces the break of dawn, others in the vicinity immediately follow. Chickens are highly social animals, and they develop a linear and fixed hierarchy in small groups. We found that when chickens were housed in small groups, the top-ranking rooster determined the timing of predawn crowing. Specifically, the top-ranking rooster always started to crow first, followed by its subordinates, in descending order of social rank. When the top-ranking rooster was physically removed from a group, the second-ranking rooster initiated crowing. The presence of a dominant rooster significantly reduced the number of predawn crows in subordinates. However, the number of crows induced by external stimuli was independent of social rank, confirming that subordinates have the ability to crow. Although the timing of subordinates' predawn crowing was strongly dependent on that of the top-ranking rooster, free-running periods of body temperature rhythms differed among individuals, and crowing rhythm did not entrain to a crowing sound stimulus. These results indicate that in a group situation, the top-ranking rooster has priority to announce the break of dawn, and that subordinate roosters are patient enough to wait for the top-ranking rooster's first crow every morning and thus compromise their circadian clock for social reasons.

Small Learning Communities Meet School-to-Work: Whole-School Restructuring for Urban Comprehensive High Schools. Report No. 31.

ERIC Educational Resources Information Center

Legters, Nettie E.

This report describes specific reform practices schools are implementing to realize the vision set forth in the National Association of Secondary School Principals document, "Breaking Ranks," which calls for changes in curriculum, instruction, assessment, school organization, professional development, community partnerships, and…

Nudge, Nudge: Teacher Interventions in Task-Based Learner Talk.

ERIC Educational Resources Information Center

Lynch, Tony

1997-01-01

Discusses whether teachers should intervene when communication between learners of English as a Second Language breaks down and, if so, what form that intervention should take. The article concludes that teachers should resist intervention at the outset of communication problems and that any subsequent intervention must be specifically tailored to…

Footing, Resistance and Control: Negotiating a Traffic Citation

ERIC Educational Resources Information Center

Smith, Wendy B.

2010-01-01

The purpose of this article is to demonstrate the micro-interactional processes by which powerful and powerless identities are locally reconstructed. The article specifically examines the interplay between consent and resistance to law-breaking identities. Data consist of transcripts of 45 incidents in which highway patrol officers issue traffic…

Incorporating "omics" in the study of reproduction and development: Virtual Tissue Models in Developmental Toxicity Research

EPA Science Inventory

In recent years, ground breaking research in genomic applications in the area of reproductive and developmental toxicology have been successful in linking changes in the expression of specific genes and their higher-level biological processes to effects induced by drugs or chemic...

Breaking News: Utilizing Video Simulations to Improve Educational Leaders' Public Speaking Skills

ERIC Educational Resources Information Center

Friend, Jennifer; Adams, April; Curry, George

2011-01-01

This article examines specific uses of video simulations in one educational leadership preparation program to advance future school and district leaders' skills related to public speaking and participation in televised news interviews. One faculty member and two advanced educational leadership candidates share their perspectives of several…

Breaking Barriers to Educational Opportunities: A Comparative Analysis of Adolescent Intervention Programs

ERIC Educational Resources Information Center

Walsh, Rachael Mae

2010-01-01

While access to education may be increasing, equity still eludes the U.S. education system, specifically for low socioeconomic status students. Using both educational and deviance theoretical frames, this study examines the effectiveness of adolescent intervention programs with respect to educational attainment and deviant behaviors. The Education…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kornfeldt, H.; Bjoerk, K.O.; Ekstroem, P.

The protection against dynamic effects in connection with potential pipe breaks has been implemented in different ways in the development of BWR reactor designs. First-generation plant designs reflect code requirements in effect at that time which means that no piping restraint systems were designed and built into those plants. Modern designs have, in contrast, implemented full protection against damage in connection with postulated pipe breaks, as required in current codes and regulations. Moderns standards and current regulatory demands can be met for the older plants by backfitting pipe whip restraint hardware. This could lead to several practical difficulties as thesemore » installations were not anticipated in the original plant design and layout. Meeting the new demands by analysis would in this situation have great advantages. Application of leak-before-break criteria gives an alternative opportunity of meeting modem standards in reactor safety design. Analysis takes into account data specific to BWR primary system operation, actual pipe material properties, piping loads and leak detection capability. Special attention must be given to ensure that the data used reflects actual plant conditions.« less

Preparation and mechanical properties of rubber composites reinforced with carbon nanohorns.

PubMed

Isshiki, Tetsuya; Hashimoto, Mikiko; Morii, Masato; Ota, Yuki; Kaneda, Kazuo; Takahashi, Hidetaka; Yudasaka, Masako; Iijima, Sumio; Okino, Fujio

2010-06-01

Nitrile butadiene rubber (NBR) composites with single-wall carbon nanohorns (SWNHs, or simply NHs), hole-opened NHs (h-NHs), and carbon black (CB), the most commonly used nanocarbon rubber filler, were prepared, and their mechanical properties were compared. The NBR composites with h-NHs (NBR/h-NH) showed higher tensile strength than those with NHs (NBR/NH), and the tensile strength of NBR/h-NH or NBR/NH was much greater than those of the NBR composites with CB (NBR/CB). At 5 parts per hundred of rubber (phr), the tensile stresses at break of NBR/h-NH was about 1.8 times larger than those of NBR/CB, and the strain at the break, 1.2 times larger. Similarly, at 20 phr, both the tensile strength and strain at the break of NBR/h-NH were 1.4 times larger than those of NBR/CB. NBR/NH showed the highest hardness while having the smallest specific gravity. The present results indicate that NHs and h-NHs have much superior reinforcement effects to CB for NBR rubber matrix.

Breaking new ground in the study and practice of alcohol brief interventions.

PubMed

Heather, Nick

2010-11-01

This article amplifies the decision to subtitle the INEBRIA2009 Conference 'Breaking New Ground'. The effectiveness of screening and brief intervention (SBI) for hazardous and harmful drinking is now well-established for primary health care and is promising for other medical settings. In addition, significant advances in the implementation of SBI are being made in various parts of the world. But, because of the need to establish efficacy and effectiveness, and perhaps too because of a preoccupation with meta-analysis of existing research findings, progress in other aspects of the theory and practice of SBI has been slower than ideal. There may also be a risk of complacency in the SBI field of study. For these reasons and others, the Conference Organizing Committee decided to focus the conference and invite presentations on a number of specific topics in the field of alcohol SBI and these are listed here followed by a discussion of other areas in which new ground needs to be broken.[Heather N. Breaking new ground in the study and practice of alcohol brief interventions. © 2010 Australasian Professional Society on Alcohol and other Drugs.

Main steam line break accident simulation of APR1400 using the model of ATLAS facility

NASA Astrophysics Data System (ADS)

Ekariansyah, A. S.; Deswandri; Sunaryo, Geni R.

2018-02-01

A main steam line break simulation for APR1400 as an advanced design of PWR has been performed using the RELAP5 code. The simulation was conducted in a model of thermal-hydraulic test facility called as ATLAS, which represents a scaled down facility of the APR1400 design. The main steam line break event is described in a open-access safety report document, in which initial conditions and assumptionsfor the analysis were utilized in performing the simulation and analysis of the selected parameter. The objective of this work was to conduct a benchmark activities by comparing the simulation results of the CESEC-III code as a conservative approach code with the results of RELAP5 as a best-estimate code. Based on the simulation results, a general similarity in the behavior of selected parameters was observed between the two codes. However the degree of accuracy still needs further research an analysis by comparing with the other best-estimate code. Uncertainties arising from the ATLAS model should be minimized by taking into account much more specific data in developing the APR1400 model.

Coal-water slurry sprays from an electronically controlled accumulator fuel injection system: Break-up distances and times

NASA Astrophysics Data System (ADS)

Caton, J. A.; Payne, S. E.; Terracina, D. P.; Kihm, K. D.

Experiments have been completed to characterize coal-water slurry sprays from an electronically-controlled accumulator fuel injection system of a diesel engine. The sprays were injected into a pressurized chamber equipped with windows. High speed movies, fuel pressures, and needle lifts were obtained as a function of time, orifice diameter, coal loading, gas density in the chamber, and accumulator fuel pressure. For the base conditions (50% by mass coal loading, 0.4 mm diameter nozzle hole, coal-water slurry pressure of 82 MPa (12,000 psi), and a chamber density of 25 kg/m(exp 3)), the break-up time was 0.30 ms. An empirical correlation for spray tip penetration, break-up time, and initial jet velocity was developed. For the conditions of this study, the spray tip penetration and initial jet velocity were 15% greater for coal-water slurry than for diesel fuel or water. Results of this study and the correlation are specific to the tested coal-water slurry and are not general for other coal-water slurry fuels.

Give me a better break: Choosing workday break activities to maximize resource recovery.

PubMed

Hunter, Emily M; Wu, Cindy

2016-02-01

Surprisingly little research investigates employee breaks at work, and even less research provides prescriptive suggestions for better workday breaks in terms of when, where, and how break activities are most beneficial. Based on the effort-recovery model and using experience sampling methodology, we examined the characteristics of employee workday breaks with 95 employees across 5 workdays. In addition, we examined resources as a mediator between break characteristics and well-being. Multilevel analysis results indicated that activities that were preferred and earlier in the work shift related to more resource recovery following the break. We also found that resources mediated the influence of preferred break activities and time of break on health symptoms and that resource recovery benefited person-level outcomes of emotional exhaustion, job satisfaction, and organizational citizenship behavior. Finally, break length interacted with the number of breaks per day such that longer breaks and frequent short breaks were associated with more resources than infrequent short breaks. (c) 2016 APA, all rights reserved).

Paleo-earthquake Analysis from the Morphologic Features of Unconsolidated-sediment Fault Scarp: An Example from Dushanzi Thrust Fault in the Northern Tianshan, China

NASA Astrophysics Data System (ADS)

Wei, Z.; He, H.

2016-12-01

Fault scarp is important specific tectonic landform caused by surface-rupture earthquake. The morphology of the fault scarp in unconsolidated sediment could evolve in a predictable, time-dependent diffusion model. As a result, the investigation of fault-generated fault scarps is a prevalent technique used to study fault activity, geomorphic evolution, and the recurrence of faulting events. Addition to obtainment of cumulative displacement, gradient changes, i.e. slope breaks, in the morphology of fault scarps could indicate multiple rupture events along an active fault. In this study, we exacted a large set of densely spaced topographic profiles across fault scarp from LiDAR-derive DEM to detect subtle changes in the fault scarp geometry at the Dushanzi trust fault in the Northern Tianshan, China. Several slope breaks in topographic profiles can be identified, which may represent repeated rupture at the investigated fault. The number of paleo-earthquakes derived from our analysis is 4-3, well in agreement with the investigation results from the paleoseismological trenches. Statistical analysis results show that the scarp height of fault scarp with one slope break is 0.75±0.12 (mean value ±1 standard deviation) m representing the last incremental displacement during earthquakes; the height of fault scarp with two slope breaks is 1.86±0.32 m, and the height of fault scarp with three-four slope break is 6.45±1.44 m. Our approach enables us to obtain paleo-earthquake information from geomorphological analysis of fault scarps, and to assess the multiple rupture history of a complex fault system.

Preliminary biocompatibility experiment of polymer films for laser-assisted tissue welding.

PubMed

Sorg, Brian S; Welch, Ashley J

2003-01-01

The purpose of this study was to examine the impact of a polymer film for liquid solder strength reinforcement on the short term healing of a wound closed by laser-tissue soldering. Full thickness incisions created on the dorsum of Sprague-Dawley rats were closed by laser-tissue soldering: albumin solder with Indocyanine Green (ICG) dye was inserted between the incision edges and photothermally coagulated with a diode laser. A poly(DL-lactic-co-glycolic acid) (PLGA) polymer film was implanted subcutaneously in the bottom of the incision (controls had no film). Specimens were harvested at 0, 3, 7, and 14 days for breaking strength testing and histological analysis. Breaking strengths of the controls at 0 and 14 days were statistically stronger than the specimens with the implanted films (t-test, P < 0.05). A slight difficulty in apposing the wound edges due to the film presence may have contributed to the low acute strengths. Interference with the wound contraction process by the films possibly contributed to the lower breaking strength at 14 days. Wound histology indicated a mild foreign body reaction to the polymer film material. The polymer film was well tolerated by the tissue, and the tissue response to the material was consistent with that seen in the literature. The breaking strength differences between control and film-implanted specimens at 0 and 14 days were probably the result of mechanical complications (tissue apposition and wound contraction) due to the presence of the film, and not due to the film material itself. The use of polymer film patches for liquid solder reinforcement and breaking strength enhancement may have certain application specific issues that need to be addressed. Strategies to account for these issues require further research. Copyright 2003 Wiley-Liss, Inc.

Atypical Role for PhoU in Mutagenic Break Repair under Stress in Escherichia coli

PubMed Central

Aponyi, Ildiko; Vera Cruz, Diana; Ray, Mellanie P.; Rosenberg, Susan M.

2015-01-01

Mechanisms of mutagenesis activated by stress responses drive pathogen/host adaptation, antibiotic and anti-fungal-drug resistance, and perhaps much of evolution generally. In Escherichia coli, repair of double-strand breaks (DSBs) by homologous recombination is high fidelity in unstressed cells, but switches to a mutagenic mode using error-prone DNA polymerases when the both the SOS and general (σS) stress responses are activated. Additionally, the σE response promotes spontaneous DNA breakage that leads to mutagenic break repair (MBR). We identified the regulatory protein PhoU in a genetic screen for functions required for MBR. PhoU negatively regulates the phosphate-transport and utilization (Pho) regulon when phosphate is in excess, including the PstB and PstC subunits of the phosphate-specific ABC transporter PstSCAB. Here, we characterize the PhoU mutation-promoting role. First, some mutations that affect phosphate transport and Pho transcriptional regulation decrease mutagenesis. Second, the mutagenesis and regulon-expression phenotypes do not correspond, revealing an apparent new function(s) for PhoU. Third, the PhoU mutagenic role is not via activation of the σS, SOS or σE responses, because mutations (or DSBs) that restore mutagenesis to cells defective in these stress responses do not restore mutagenesis to phoU cells. Fourth, the mutagenesis defect in phoU-mutant cells is partially restored by deletion of arcA, a gene normally repressed by PhoU, implying that a gene(s) repressed by ArcA promotes mutagenic break repair. The data show a new role for PhoU in regulation, and a new regulatory branch of the stress-response signaling web that activates mutagenic break repair in E. coli. PMID:25961709

A computer-based specification methodology

NASA Technical Reports Server (NTRS)

Munck, Robert G.

1986-01-01

Standard practices for creating and using system specifications are inadequate for large, advanced-technology systems. A need exists to break away from paper documents in favor of documents that are stored in computers and which are read and otherwise used with the help of computers. An SADT-based system, running on the proposed Space Station data management network, could be a powerful tool for doing much of the required technical work of the Station, including creating and operating the network itself.

Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break.

PubMed

Anderson, Carol M; Korkin, Dmitry; Smith, Dana L; Makovets, Svetlana; Seidel, Jeffrey J; Sali, Andrej; Blackburn, Elizabeth H

2008-04-01

The kinases ATM and ATR (Tel1 and Mec1 in the yeast Saccharomyces cerevisiae) control the response to DNA damage. We report that S. cerevisiae Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling. We show that Tel1 and Tel2 interact, and that even when Tel1 protein levels are high, this interaction is specifically required for Tel1 localization to a DNA break and its activation of downstream targets. Computational analysis revealed structural homology between Tel2 and Ddc2 (ATRIP in vertebrates), a partner of Mec1, suggesting a common structural principle used by partners of phoshoinositide 3-kinase-like kinases.

Synthetic antibodies: concepts, potential and practical considerations.

PubMed

Miersch, S; Sidhu, S S

2012-08-01

The last 100 years of enquiry into the fundamental basis of humoral immunity has resulted in the identification of antibodies as key molecular sentinels responsible for the in vivo surveillance, neutralization and clearance of foreign substances. Intense efforts aimed at understanding and exploiting their exquisite molecular specificity have positioned antibodies as a cornerstone supporting basic research, diagnostics and therapeutic applications [1]. More recently, efforts have aimed to circumvent the limitations of developing antibodies in animals by developing wholly in vitro techniques for designing antibodies of tailored specificity. This has been realized with the advent of synthetic antibody libraries that possess diversity outside the scope of natural immune repertoires and are thus capable of yielding specificities not otherwise attainable. This review examines the convergence of technologies that have contributed to the development of combinatorial phage-displayed antibody libraries. It further explores the practical concepts that underlie phage display, antibody diversity and the methods used in the generation of and selection from phage-displayed synthetic antibody libraries, highlighting specific applications in which design approaches gave rise to specificities that could not easily be obtained with libraries based upon natural immune repertories. Copyright © 2012 Elsevier Inc. All rights reserved.

Human seizures couple across spatial scales through travelling wave dynamics

NASA Astrophysics Data System (ADS)

Martinet, L.-E.; Fiddyment, G.; Madsen, J. R.; Eskandar, E. N.; Truccolo, W.; Eden, U. T.; Cash, S. S.; Kramer, M. A.

2017-04-01

Epilepsy--the propensity toward recurrent, unprovoked seizures--is a devastating disease affecting 65 million people worldwide. Understanding and treating this disease remains a challenge, as seizures manifest through mechanisms and features that span spatial and temporal scales. Here we address this challenge through the analysis and modelling of human brain voltage activity recorded simultaneously across microscopic and macroscopic spatial scales. We show that during seizure large-scale neural populations spanning centimetres of cortex coordinate with small neural groups spanning cortical columns, and provide evidence that rapidly propagating waves of activity underlie this increased inter-scale coupling. We develop a corresponding computational model to propose specific mechanisms--namely, the effects of an increased extracellular potassium concentration diffusing in space--that support the observed spatiotemporal dynamics. Understanding the multi-scale, spatiotemporal dynamics of human seizures--and connecting these dynamics to specific biological mechanisms--promises new insights to treat this devastating disease.

Lysyl oxidase: properties, specificity, and biological roles inside and outside of the cell.

PubMed

Kagan, Herbert M; Li, Wande

2003-03-01

Lysyl oxidase (LO) plays a critical role in the formation and repair of the extracellular matrix (ECM) by oxidizing lysine residues in elastin and collagen, thereby initiating the formation of covalent crosslinkages which stabilize these fibrous proteins. Its catalytic activity depends upon both its copper cofactor and a unique carbonyl cofactor and has been shown to extend to a variety of basic globular proteins, including histone H1. Although the three-dimensional structure of LO has yet to be determined, the present treatise offers hypotheses based upon its primary sequence, which may underlie the prominent electrostatic component of its unusual substrate specificity as well as the catalysis-suppressing function of the propeptide domain of prolysyl oxidase. Recent studies have demonstrated that LO appears to function within the cell in a manner, which strongly modifies cellular activity. Newly discovered LO-like proteins also likely play unique roles in biology. Copyright 2002 Wiley-Liss, Inc.

Global Characteristics of Childhood Acute Promyelocytic Leukemia

PubMed Central

Zhang, L; Samad, A; Pombo-de-Oliveira, MS; Scelo, G; Smith, MT; Feusner, J; Wiemels, JL; Metayer, C

2014-01-01

Acute promyelocytic leukemia (APL) comprises approximately 5–10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning >60 countries) identified, variation was apparent—de novo APL represented from 2% (Switzerland) to >50% (Nicaragua) of childhood AML in different geographic regions. Because a limited number of previous studies addressed specific environmental exposures that potentially underlie childhood APL development, we gathered 28 childhood cases of therapy-related APL, which exemplified associations between prior exposures to chemotherapeutic drugs/radiation and APL diagnosis. Future population-based studies examining childhood APL patterns and the potential association with specific environmental exposures and other risk factors are needed. PMID:25445717

Predicting homophobic behavior among heterosexual youth: domain general and sexual orientation-specific factors at the individual and contextual level.

PubMed

Poteat, V Paul; DiGiovanni, Craig D; Scheer, Jillian R

2013-03-01

As a form of bias-based harassment, homophobic behavior remains prominent in schools. Yet, little attention has been given to factors that underlie it, aside from bullying and sexual prejudice. Thus, we examined multiple domain general (empathy, perspective-taking, classroom respect norms) and sexual orientation-specific factors (sexual orientation identity importance, number of sexual minority friends, parents' sexual minority attitudes, media messages). We documented support for a model in which these sets of factors converged to predict homophobic behavior, mediated through bullying and prejudice, among 581 students in grades 9-12 (55 % female). The structural equation model indicated that, with the exception of media messages, these additional factors predicted levels of prejudice and bullying, which in turn predicted the likelihood of students to engage in homophobic behavior. These findings highlight the importance of addressing multiple interrelated factors in efforts to reduce bullying, prejudice, and discrimination among youth.

A neural command circuit for grooming movement control.

PubMed

Hampel, Stefanie; Franconville, Romain; Simpson, Julie H; Seeds, Andrew M

2015-09-07

Animals perform many stereotyped movements, but how nervous systems are organized for controlling specific movements remains unclear. Here we use anatomical, optogenetic, behavioral, and physiological techniques to identify a circuit in Drosophila melanogaster that can elicit stereotyped leg movements that groom the antennae. Mechanosensory chordotonal neurons detect displacements of the antennae and excite three different classes of functionally connected interneurons, which include two classes of brain interneurons and different parallel descending neurons. This multilayered circuit is organized such that neurons within each layer are sufficient to specifically elicit antennal grooming. However, we find differences in the durations of antennal grooming elicited by neurons in the different layers, suggesting that the circuit is organized to both command antennal grooming and control its duration. As similar features underlie stimulus-induced movements in other animals, we infer the possibility of a common circuit organization for movement control that can be dissected in Drosophila.

Preeclampsia and the Future Risk of Hypertension: The Pregnant Evidence

PubMed Central

Garovic, Vesna D.; August, Phyllis

2013-01-01

Cardiovascular death rates continue to rise for women under age 55, underlying the importance of focusing on female-specific conditions that may increase cardiovascular risk, including pregnancy-related disorders. Hypertension complicates about 5–10% of pregnancies. Preeclampsia, a pregnancy-specific condition, is characterized by hypertension and proteinuria after 20 weeks of gestation and remains one of the major causes of maternal deaths in the United States. In addition, preeclampsia may have an impact on women’s health beyond their pregnancies, and has been associated with increased risks for future hypertension and cardiovascular disease, such as coronary heart disease and stroke. In this review, we discuss the evidence supporting the association between preeclampsia and future hypertension; possible mechanisms that underlie this association; current approach to women with a history of preeclampsia; and future research that is needed in this field in order to deliver optimal and timely medical care to the affected women. PMID:23397213

Epigenetic impacts of endocrine disruptors in the brain☆

PubMed Central

Walker, Deena M.; Gore, Andrea C.

2017-01-01

The acquisition of reproductive competence is organized and activated by steroid hormones acting upon the hypothalamus during critical windows of development. This review describes the potential role of epigenetic processes, particularly DNA methylation, in the regulation of sexual differentiation of the hypothalamus by hormones. We examine disruption of these processes by endocrine-disrupting chemicals (EDCs) in an age-, sex-, and region-specific manner, focusing on how perinatal EDCs act through epigenetic mechanisms to reprogram DNA methylation and sex steroid hormone receptor expression throughout life. These receptors are necessary for brain sexual differentiation and their altered expression may underlie disrupted reproductive physiology and behavior. Finally, we review the literature on histone modifications and non-coding RNA involvement in brain sexual differentiation and their perturbation by EDCs. By putting these data into a sex and developmental context we conclude that perinatal EDC exposure alters the developmental trajectory of reproductive neuroendocrine systems in a sex-specific manner. PMID:27663243

Theta-burst microstimulation in the human entorhinal area improves memory specificity.

PubMed

Titiz, Ali S; Hill, Michael R H; Mankin, Emily A; M Aghajan, Zahra; Eliashiv, Dawn; Tchemodanov, Natalia; Maoz, Uri; Stern, John; Tran, Michelle E; Schuette, Peter; Behnke, Eric; Suthana, Nanthia A; Fried, Itzhak

2017-10-24

The hippocampus is critical for episodic memory, and synaptic changes induced by long-term potentiation (LTP) are thought to underlie memory formation. In rodents, hippocampal LTP may be induced through electrical stimulation of the perforant path. To test whether similar techniques could improve episodic memory in humans, we implemented a microstimulation technique that allowed delivery of low-current electrical stimulation via 100 μm -diameter microelectrodes. As thirteen neurosurgical patients performed a person recognition task, microstimulation was applied in a theta-burst pattern, shown to optimally induce LTP. Microstimulation in the right entorhinal area during learning significantly improved subsequent memory specificity for novel portraits; participants were able both to recognize previously-viewed photos and reject similar lures. These results suggest that microstimulation with physiologic level currents-a radical departure from commonly used deep brain stimulation protocols-is sufficient to modulate human behavior and provides an avenue for refined interrogation of the circuits involved in human memory.

Biosynthesis of Modular Ascarosides in C. elegans

PubMed Central

Panda, Oishika; Akagi, Allison E.; Artyukhin, Alexander B.; Judkins, Joshua C.; Le, Henry H.; Mahanti, Parag; Cohen, Sarah M.; Sternberg, Paul W.

2017-01-01

The nematode Caenorhabditis elegans uses simple building blocks from primary metabolism and a strategy of modular assembly to build a great diversity of signaling molecules, the ascarosides, which function as a chemical language in this model organism. In the ascarosides, the dideoxysugar ascarylose serves as a scaffold to which diverse moieties from lipid, amino acid, neurotransmitter, and nucleoside metabolism are attached. However, the mechanisms that underlie the highly specific assembly of ascarosides are not understood. We show that the acyl-CoA synthetase ACS-7, which localizes to lysosome-related organelles, is specifically required for the attachment of different building blocks to the 4′-position of ascr#9. We further show that mutants lacking lysosome-related organelles are defective in the production of all 4′-modified ascarosides, thus identifying the waste disposal system of the cell as a hotspot for ascaroside biosynthesis. PMID:28371259

Brain Oscillations, Hypnosis, and Hypnotizability

PubMed Central

Jensen, Mark P.; Adachi, Tomonori; Hakimian, Shahin

2014-01-01

In this article, we summarize the state-of-science knowledge regarding the associations between hypnosis and brain oscillations. Brain oscillations represent the combined electrical activity of neuronal assemblies, and are usually measured as specific frequencies representing slower (delta, theta, alpha) and faster (beta, gamma) oscillations. Hypnosis has been most closely linked to power in the theta band and changes in gamma activity. These oscillations are thought to play a critical role in both the recording and recall of declarative memory and emotional limbic circuits. Here we propose that it is this role that may be the mechanistic link between theta (and perhaps gamma) oscillations and hypnosis; specifically that theta oscillations may facilitate, and that changes in gamma activity observed with hypnosis may underlie, some hypnotic responses. If these hypotheses are supported, they have important implications for both understanding the effects of hypnosis, and for enhancing response to hypnotic treatments. PMID:25792761

Interregional synaptic maps among engram cells underlie memory formation.

PubMed

Choi, Jun-Hyeok; Sim, Su-Eon; Kim, Ji-Il; Choi, Dong Il; Oh, Jihae; Ye, Sanghyun; Lee, Jaehyun; Kim, TaeHyun; Ko, Hyoung-Gon; Lim, Chae-Seok; Kaang, Bong-Kiun

2018-04-27

Memory resides in engram cells distributed across the brain. However, the site-specific substrate within these engram cells remains theoretical, even though it is generally accepted that synaptic plasticity encodes memories. We developed the dual-eGRASP (green fluorescent protein reconstitution across synaptic partners) technique to examine synapses between engram cells to identify the specific neuronal site for memory storage. We found an increased number and size of spines on CA1 engram cells receiving input from CA3 engram cells. In contextual fear conditioning, this enhanced connectivity between engram cells encoded memory strength. CA3 engram to CA1 engram projections strongly occluded long-term potentiation. These results indicate that enhanced structural and functional connectivity between engram cells across two directly connected brain regions forms the synaptic correlate for memory formation. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Tissue-specific mechanical and geometrical control of cell viability and actin cytoskeleton alignment

NASA Astrophysics Data System (ADS)

Wang, Dong; Zheng, Wenfu; Xie, Yunyan; Gong, Peiyuan; Zhao, Fang; Yuan, Bo; Ma, Wanshun; Cui, Yan; Liu, Wenwen; Sun, Yi; Piel, Matthieu; Zhang, Wei; Jiang, Xingyu

2014-08-01

Different tissues have specific mechanical properties and cells of different geometries, such as elongated muscle cells and polygonal endothelial cells, which are precisely regulated during embryo development. However, the mechanisms that underlie these processes are not clear. Here, we built an in vitro model to mimic the cellular microenvironment of muscle by combining both mechanical stretch and geometrical control. We found that mechanical stretch was a key factor that determined the optimal geometry of myoblast C2C12 cells under stretch, whereas vascular endothelial cells and fibroblasts had no such dependency. We presented the first experimental evidence that can explain why myoblasts are destined to take the elongated geometry so as to survive and maintain parallel actin filaments along the stretching direction. The study is not only meaningful for the research on myogenesis but also has potential application in regenerative medicine.

Interpreting sperm DNA damage in a diverse range of mammalian sperm by means of the two-tailed comet assay

PubMed Central

Cortés-Gutiérrez, Elva I.; López-Fernández, Carmen; Fernández, José Luis; Dávila-Rodríguez, Martha I.; Johnston, Stephen D.; Gosálvez, Jaime

2014-01-01

Key Concepts The two-dimensional Two-Tailed Comet assay (TT-comet) protocol is a valuable technique to differentiate between single-stranded (SSBs) and double-stranded DNA breaks (DSBs) on the same sperm cell.Protein lysis inherent with the TT-comet protocol accounts for differences in sperm protamine composition at a species-specific level to produce reliable visualization of sperm DNA damage.Alkaline treatment may break the sugar–phosphate backbone in abasic sites or at sites with deoxyribose damage, transforming these lesions into DNA breaks that are also converted into ssDNA. These lesions are known as Alkali Labile Sites “ALSs.”DBD–FISH permits the in situ visualization of DNA breaks, abasic sites or alkaline-sensitive DNA regions.The alkaline comet single assay reveals that all mammalian species display constitutive ALS related with the requirement of the sperm to undergo transient changes in DNA structure linked with chromatin packing.Sperm DNA damage is associated with fertilization failure, impaired pre-and post- embryo implantation and poor pregnancy outcome.The TT is a valuable tool for identifying SSBs or DSBs in sperm cells with DNA fragmentation and can be therefore used for the purposes of fertility assessment. Sperm DNA damage is associated with fertilization failure, impaired pre-and post- embryo implantation and poor pregnancy outcome. A series of methodologies to assess DNA damage in spermatozoa have been developed but most are unable to differentiate between single-stranded DNA breaks (SSBs) and double-stranded DNA breaks (DSBs) on the same sperm cell. The two-dimensional Two-Tailed Comet assay (TT-comet) protocol highlighted in this review overcomes this limitation and emphasizes the importance in accounting for the difference in sperm protamine composition at a species-specific level for the appropriate preparation of the assay. The TT-comet is a modification of the original comet assay that uses a two dimensional electrophoresis to allow for the simultaneous evaluation of DSBs and SSBs in mammalian spermatozoa. Here we have compiled a retrospective overview of how the TT-comet assay has been used to investigate the structure and function of sperm DNA across a diverse range of mammalian species (eutheria, metatheria, and prototheria). When conducted as part of the TT-comet assay, we illustrate (a) how the alkaline comet single assay has been used to help understand the constitutive and transient changes in DNA structure associated with chromatin packing, (b) the capacity of the TT-comet to differentiate between the presence of SSBs and DSBs (c) and the possible implications of SSBs or DSBs for the assessment of infertility. PMID:25505901

Plant developmental responses to climate change.

PubMed

Gray, Sharon B; Brady, Siobhan M

2016-11-01

Climate change is multi-faceted, and includes changing concentrations of greenhouse gases in the atmosphere, rising temperatures, changes in precipitation patterns, and increasing frequency of extreme weather events. Here, we focus on the effects of rising atmospheric CO 2 concentrations, rising temperature, and drought stress and their interaction on plant developmental processes in leaves, roots, and in reproductive structures. While in some cases these responses are conserved across species, such as decreased root elongation, perturbation of root growth angle and reduced seed yield in response to drought, or an increase in root biomass in shallow soil in response to elevated CO 2 , most responses are variable within and between species and are dependent on developmental stage. These variable responses include species-specific thresholds that arrest development of reproductive structures, reduce root growth rate and the rate of leaf initiation and expansion in response to elevated temperature. Leaf developmental responses to elevated CO 2 vary by cell type and by species. Variability also exists between C 3 and C 4 species in response to elevated CO 2 , especially in terms of growth and seed yield stimulation. At the molecular level, significantly less is understood regarding conservation and variability in molecular mechanisms underlying these traits. Abscisic acid-mediated changes in cell wall expansion likely underlie reductions in growth rate in response to drought, and changes in known regulators of flowering time likely underlie altered reproductive transitions in response to elevated temperature and CO 2 . Genes that underlie most other organ or tissue-level responses have largely only been identified in a single species in response to a single stress and their level of conservation is unknown. We conclude that there is a need for further research regarding the molecular mechanisms of plant developmental responses to climate change factors in general, and that this lack of data is particularly prevalent in the case of interactive effects of multiple climate change factors. As future growing conditions will likely expose plants to multiple climate change factors simultaneously, with a sum negative influence on global agriculture, further research in this area is critical. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Phosphorylation of FMRP and alterations of FMRP complex underlie enhanced mLTD in adult rats triggered by early life seizures.

PubMed

Bernard, Paul B; Castano, Anna M; O'Leary, Heather; Simpson, Kameron; Browning, Michael D; Benke, Tim A

2013-11-01

Outside of Fragile X syndrome (FXS), the role of Fragile-X Mental Retardation Protein (FMRP) in mediating neuropsychological abnormalities is not clear. FMRP, p70-S6 kinase (S6K) and protein phosphatase 2A (PP2A) are thought to cooperate as a dynamic signaling complex. In our prior work, adult rats have enhanced CA1 hippocampal long-term depression (LTD) following an early life seizure (ELS). We now show that mGluR-mediated LTD (mLTD) is specifically enhanced following ELS, similar to FMRP knock-outs. Total FMRP expression is unchanged but S6K is hyperphosphorylated, consistent with S6K overactivation. We postulated that either disruption of the FMRP-S6K-PP2A complex and/or removal of this complex from synapses could explain our findings. Using subcellular fractionation, we were surprised to find that concentrations of FMRP and PP2A were undisturbed in the synaptosomal compartment but reduced in parallel in the cytosolic compartment. Following ELS FMRP phosphorylation was reduced in the cytosolic compartment and increased in the synaptic compartment, in parallel with the compartmentalization of S6K activation. Furthermore, FMRP and PP2A remain bound following ELS. In contrast, the interaction of S6K with FMRP is reduced by ELS. Blockade of PP2A results in enhanced mLTD; this is occluded by ELS. This suggests a critical role for the location and function of the FMRP-S6K-PP2A signaling complex in limiting the amount of mLTD. Specifically, non-synaptic targeting and the function of the complex may influence the "set-point" for regulating mLTD. Consistent with this, striatal-enriched protein tyrosine phosphatase (STEP), an FMRP "target" which regulates mLTD expression, is specifically increased in the synaptosomal compartment following ELS. Further, we provide behavioral data to suggest that FMRP complex dysfunction may underlie altered socialization, a symptom associated and observed in other rodent models of autism, including FXS. © 2013.

PIERCE1 is critical for specification of left-right asymmetry in mice.

PubMed

Sung, Young Hoon; Baek, In-Jeoung; Kim, Yong Hwan; Gho, Yong Song; Oh, S Paul; Lee, Young Jae; Lee, Han-Woong

2016-06-16

The specification of left-right asymmetry of the visceral organs is precisely regulated. The earliest breakage of left-right symmetry occurs as the result of leftward flow generated by asymmetric beating of nodal cilia, which eventually induces asymmetric Nodal/Lefty/Pitx2 expression on the left side of the lateral plate mesoderm. PIERCE1 has been identified as a p53 target gene involved in the DNA damage response. In this study, we found that Pierce1-null mice exhibit severe laterality defects, including situs inversus totalis and heterotaxy with randomized situs and left and right isomerisms. The spectrum of laterality defects was closely correlated with randomized expression of Nodal and its downstream genes, Lefty1/2 and Pitx2. The phenotype of Pierce1-null mice most closely resembled that of mutant mice with impaired ciliogenesis and/or ciliary motility of the node. We also found the loss of asymmetric expression of Cerl2, the earliest flow-responding gene in the node of Pierce1-null embryos. The results suggest that Pierce1-null embryos have defects in generating a symmetry breaking signal including leftward nodal flow. This is the first report implicating a role for PIERCE1 in the symmetry-breaking step of left-right asymmetry specification.

Breaking open the set top box

NASA Astrophysics Data System (ADS)

Banks, David; Wiley, Anthony; Catania, Nicolas; Coles, Alastair N.; Smith, Duncan; Baynham, Simon; Deliot, Eric; Chidzey, Rod

1998-02-01

In this paper we describe the work being done at HP Labs Bristol in the area of home networks and gateways. This work is based on the idea of breaking open the set top box by physically separating the access network specific functions from the application specific functions. The access network specific functions reside in an access network gateway that can be shared by many end user devices. The first section of the paper present the philosophy behind this approach. The end user devices and the access network gateways must be interconnected by a high bandwidth network which can offer a bounded delay service for delay sensitive traffic. We are advocating the use of IEEE 1394 for this network, and the next section of the paper gives a brief introduction to this technology. We then describe a prototype digital video broadcasting satellite compliant gateway that we have built. This gateway could be used, for example, by a PC for receiving a data service or by a digital TV for receiving an MPEG-2 video service. A control architecture is the presented which uses a PC application to provide a web based user interface to the system. Finally, we provide details of our work on extending the reach of IEEE 1394 and its standardization status.

Sites of instability in the human TCF3 (E2A) gene adopt G-quadruplex DNA structures in vitro

PubMed Central

Williams, Jonathan D.; Fleetwood, Sara; Berroyer, Alexandra; Kim, Nayun; Larson, Erik D.

2015-01-01

The formation of highly stable four-stranded DNA, called G-quadruplex (G4), promotes site-specific genome instability. G4 DNA structures fold from repetitive guanine sequences, and increasing experimental evidence connects G4 sequence motifs with specific gene rearrangements. The human transcription factor 3 (TCF3) gene (also termed E2A) is subject to genetic instability associated with severe disease, most notably a common translocation event t(1;19) associated with acute lymphoblastic leukemia. The sites of instability in TCF3 are not randomly distributed, but focused to certain sequences. We asked if G4 DNA formation could explain why TCF3 is prone to recombination and mutagenesis. Here we demonstrate that sequences surrounding the major t(1;19) break site and a region associated with copy number variations both contain G4 sequence motifs. The motifs identified readily adopt G4 DNA structures that are stable enough to interfere with DNA synthesis in physiological salt conditions in vitro. When introduced into the yeast genome, TCF3 G4 motifs promoted gross chromosomal rearrangements in a transcription-dependent manner. Our results provide a molecular rationale for the site-specific instability of human TCF3, suggesting that G4 DNA structures contribute to oncogenic DNA breaks and recombination. PMID:26029241

Meiotic Recombination Initiated by a Double-Strand Break in Rad50Δ Yeast Cells Otherwise Unable to Initiate Meiotic Recombination

PubMed Central

Malkova, A.; Ross, L.; Dawson, D.; Hoekstra, M. F.; Haber, J. E.

1996-01-01

Meiotic recombination in Saccharomyces cerevisiae is initiated by double-strand breaks (DSBs). We have developed a system to compare the properties of meiotic DSBs with those created by the site-specific HO endonuclease. HO endonuclease was expressed under the control of the meiotic-specific SPO13 promoter, creating a DSB at a single site on one of yeast's 16 chromosomes. In Rad(+) strains the times of appearance of the HO-induced DSBs and of subsequent recombinants are coincident with those induced by normal meiotic DSBs. Physical monitoring of DNA showed that SPO13::HO induced gene conversions both in Rad(+) and in rad50Δ cells that cannot initiate normal meiotic DSBs. We find that the RAD50 gene is important, but not essential, for recombination even after a DSB has been created in a meiotic cell. In rad50Δ cells, some DSBs are not repaired until a broken chromosome has been packaged into a spore and is subsequently germinated. This suggests that a broken chromosome does not signal an arrest of progression through meiosis. The recombination defect in rad50Δ diploids is not, however, meiotic specific, as mitotic rad50 diploids, experiencing an HO-induced DSB, exhibit similar departures from wild-type recombination. PMID:8725223

Prediction and redesign of protein–protein interactions

PubMed Central

Lua, Rhonald C.; Marciano, David C.; Katsonis, Panagiotis; Adikesavan, Anbu K.; Wilkins, Angela D.; Lichtarge, Olivier

2014-01-01

Understanding the molecular basis of protein function remains a central goal of biology, with the hope to elucidate the role of human genes in health and in disease, and to rationally design therapies through targeted molecular perturbations. We review here some of the computational techniques and resources available for characterizing a critical aspect of protein function – those mediated by protein–protein interactions (PPI). We describe several applications and recent successes of the Evolutionary Trace (ET) in identifying molecular events and shapes that underlie protein function and specificity in both eukaryotes and prokaryotes. ET is a part of analytical approaches based on the successes and failures of evolution that enable the rational control of PPI. PMID:24878423

Shift in speed selectivity of visual cortical neurons: A neural basis of perceived motion contrast

PubMed Central

Li, Chao-Yi; Lei, Jing-Jiang; Yao, Hai-Shan

1999-01-01

The perceived speed of motion in one part of the visual field is influenced by the speed of motion in its surrounding fields. Little is known about the cellular mechanisms causing this phenomenon. Recordings from mammalian visual cortex revealed that speed preference of the cortical cells could be changed by displaying a contrast speed in the field surrounding the cell’s classical receptive field. The neuron’s selectivity shifted to prefer faster speed if the contextual surround motion was set at a relatively lower speed, and vice versa. These specific center–surround interactions may underlie the perceptual enhancement of speed contrast between adjacent fields. PMID:10097161

The dynamic lift of developmental process.

PubMed

Smith, Linda B; Breazeal, Cynthia

2007-01-01

What are the essential properties of human intelligence, currently unparalleled in its power relative to other biological forms and relative to artificial forms of intelligence? We suggest that answering this question depends critically on understanding developmental process. This paper considers three principles potentially essential to building human-like intelligence: the heterogeneity of the component processes, the embedding of development in a social world, and developmental processes that change the cognitive system as a function of the history of soft-assemblies of these heterogeneous processes in specific tasks. The paper uses examples from human development and from developmental robotics to show how these processes also may underlie biological intelligence and enable us to generate more advanced forms of artificial intelligence.

Perceptual processing affects conceptual processing.

PubMed

Van Dantzig, Saskia; Pecher, Diane; Zeelenberg, René; Barsalou, Lawrence W

2008-04-05

According to the Perceptual Symbols Theory of cognition (Barsalou, 1999), modality-specific simulations underlie the representation of concepts. A strong prediction of this view is that perceptual processing affects conceptual processing. In this study, participants performed a perceptual detection task and a conceptual property-verification task in alternation. Responses on the property-verification task were slower for those trials that were preceded by a perceptual trial in a different modality than for those that were preceded by a perceptual trial in the same modality. This finding of a modality-switch effect across perceptual processing and conceptual processing supports the hypothesis that perceptual and conceptual representations are partially based on the same systems. 2008 Cognitive Science Society, Inc.

Consciousness and body image: lessons from phantom limbs, Capgras syndrome and pain asymbolia.

PubMed Central

Ramachandran, V S

1998-01-01

Words such as 'consciousness' and 'self' actually encompass a number of distinct phenomena that are loosely lumped together. The study of neurological syndromes allows us to explore the neural mechanisms that might underlie different aspects of self, such as body image and emotional responses to sensory stimuli, and perhaps even laughter and humour. Mapping the 'functional logic' of the many different attributes of human nature on to specific neural circuits in the brain offers the best hope of understanding how the activity of neurons gives rise to conscious experience. We consider three neurological syndromes (phantom limbs, Capgras delusion and pain asymbolia) to illustrate this idea. PMID:9854257

Understanding complex host-microbe interactions in Hydra

PubMed Central

Bosch, Thomas C.G.

2012-01-01

Any multicellular organism may be considered a metaorganism or holobiont—comprised of the macroscopic host and synergistic interdependence with bacteria, archaea, fungi, viruses, and numerous other microbial and eukaryotic species including algal symbionts. Defining the individual microbe-host conversations in these consortia is a challenging but necessary step on the path to understanding the function of the associations as a whole. Dissecting the fundamental principles that underlie all host-microbe interactions requires simple animal models with only a few specific bacterial species. Here I present Hydra as such a model with one of the simplest epithelia in the animal kingdom, with the availability of a fully sequenced genome and numerous genomic tools, and with few associated bacterial species. PMID:22688725

Stirring images: fear, not happiness or arousal, makes art more sublime.

PubMed

Eskine, Kendall J; Kacinik, Natalie A; Prinz, Jesse J

2012-10-01

Which emotions underlie our positive experiences of art? Although recent evidence from neuroscience suggests that emotions play a critical role in art perception, no research to date has explored the extent to which specific emotional states affect aesthetic experiences or whether general physiological arousal is sufficient. Participants were assigned to one of five conditions-sitting normally, engaging in 15 or 30 jumping jacks, or viewing a happy or scary video-prior to rating abstract works of art. Only the fear condition resulted in significantly more positive judgments about the art. These striking findings provide the first evidence that fear uniquely inspires positively valenced aesthetic judgments. The results are discussed in the context of embodied cognition.

Synapse Specificity of Long-Term Potentiation Breaks Down with Aging

ERIC Educational Resources Information Center

Ris, Laurence; Godaux, Emile

2007-01-01

Memory shows age-related decline. According to the current prevailing theoretical model, encoding of memories relies on modifications in the strength of the synapses connecting the different cells within a neuronal network. The selective increases in synaptic weight are thought to be biologically implemented by long-term potentiation (LTP). Here,…

The Research Proposal in Biomechanical and Biological Engineering Courses

ERIC Educational Resources Information Center

Harrison, Roger G.; Nollert, Matthias U.; Schmidtke, David W.; Sikavitsas, Vassilios I.

2006-01-01

Students in four biochemical and biological engineering courses for upper-­level undergraduates and graduate students were required to write a research proposal. Breaking the requirements down into segments (such as a summary with specific aims, rough draft, and final draft) due on different dates helped make the assignment more manageable for the…

Identification of Proteins Required for Repair of Double-Strand Chromosome Breaks, a Predisposing Factor in Breast Cancer

DTIC Science & Technology

2001-06-01

enzymatic apparatus needed to initiate DNA replication on recombination intermediates. Escherichia coli PriA protein was found to play a critical function in...the transition from recombination to DNA replication . PriA specifically binds to forked DNA structures created by recombination or replication fork

Assessment of Matrix Multiplication Learning with a Rule-Based Analytical Model--"A Bayesian Network Representation"

ERIC Educational Resources Information Center

Zhang, Zhidong

2016-01-01

This study explored an alternative assessment procedure to examine learning trajectories of matrix multiplication. It took rule-based analytical and cognitive task analysis methods specifically to break down operation rules for a given matrix multiplication. Based on the analysis results, a hierarchical Bayesian network, an assessment model,…

Reaching Out: A Break from Traditional Forensic Events. "On Interpretation Analysis."

ERIC Educational Resources Information Center

Seney, Ronald J.

In recent years a new event called "Interpretation Analysis" has appeared at certain forensic events. The objective is for the student, through analysis and performance, to study a piece of literature and to communicate his or her understanding of that literature to a specific audience. Perhaps there is room within the established…

Breaking the Silence: The Unionization of Postdoctoral Workers at the University of California

ERIC Educational Resources Information Center

Camacho, Sayil; Rhoads, Robert A.

2015-01-01

This article examines the postdoctoral unionization movement at the University of California (UC) using case study methodology. More specifically, we examine postdoctoral union organizers involved in the United Automobile Workers of America (UAW) Local 5810, focusing on their efforts to unionize postdoctoral employees at the UC. The study is…

One World Is Not Enough: Examining the Implications of Historical Objectivity

ERIC Educational Resources Information Center

Perrier, Craig J.

2007-01-01

Contemporary secondary education is marked by the standardization of both content and testing. The effect of this characterization on history, the humanities, and social studies results in a break from the spirit of these disciplines. Regarding history, the specific implications include objectification of causation and "the truth" about the past,…

Exploring the Role of Alternative Break Programs in Students' Career Development

ERIC Educational Resources Information Center

Niehaus, Elizabeth; Kurotsuchi Inkelas, Karen

2015-01-01

Higher education institutions play a key role in helping to shape students' interests and career plans; as such, student affairs practitioners should understand how the co-curricular environments in their domain contribute to students' career development. The purpose of this study is to explore how one specific co-curricular experience,…

Directed Self-Inquiry: A Scaffold for Teaching Laboratory Report Writing

ERIC Educational Resources Information Center

Deiner, L. Jay; Newsome, Daniel; Samaroo, Diana

2012-01-01

A scaffold was created for the explicit instruction of laboratory report writing. The scaffold breaks the laboratory report into sections and teaches students to ask and answer questions in order to generate section-appropriate content and language. Implementation of the scaffold is done through a series of section-specific worksheets that are…

NetWork News. Number 21, Fall 2005

ERIC Educational Resources Information Center

Learning Point Associates / North Central Regional Educational Laboratory (NCREL), 2005

2005-01-01

An Interview With Kiley Walsh In her ground-breaking study, titled "After the Test: How Schools Are Using Data to Close the Achievement Gap", researcher Kiley Walsh shows clear evidence of specific work being done to close achievement gaps. Walsh selected 32 schools across six counties in the San Francisco Bay Area and compared those…

DNA Repair Mechanisms and Their Biological Roles in the Malaria Parasite Plasmodium falciparum

PubMed Central

Lee, Andrew H.; Symington, Lorraine S.

2014-01-01

SUMMARY Research into the complex genetic underpinnings of the malaria parasite Plasmodium falciparum is entering a new era with the arrival of site-specific genome engineering. Previously restricted only to model systems but now expanded to most laboratory organisms, and even to humans for experimental gene therapy studies, this technology allows researchers to rapidly generate previously unattainable genetic modifications. This technological advance is dependent on DNA double-strand break repair (DSBR), specifically homologous recombination in the case of Plasmodium. Our understanding of DSBR in malaria parasites, however, is based largely on assumptions and knowledge taken from other model systems, which do not always hold true in Plasmodium. Here we describe the causes of double-strand breaks, the mechanisms of DSBR, and the differences between model systems and P. falciparum. These mechanisms drive basic parasite functions, such as meiosis, antigen diversification, and copy number variation, and allow the parasite to continually evolve in the contexts of host immune pressure and drug selection. Finally, we discuss the new technologies that leverage DSBR mechanisms to accelerate genetic investigations into this global infectious pathogen. PMID:25184562

Identifying and Retaining Quality Naval Officers: A Quantitative Analysis of Job Matching and Lateral Transfers

DTIC Science & Technology

2017-03-01

Mundell, 2016, p. 49). 22 For the sake of this thesis, it is important to note the specifics of Mundell’s (2016) research , as to provide a comparative ...his research did not first break out designation changes by specific community or year, but rather grouped all transfers at the four-, six-, and... compared to Naval Academy graduates, regardless of URL or RL/Staff community designation . 55 Table 13. MSR Retention Model Results by

Aeronautical Situational Awareness - Airport Surface

NASA Technical Reports Server (NTRS)

Linetsky, Vladimir M.; Ivancic, William D.; Vaden, Karl R.

2017-01-01

This paper advocates for a specific design approach, based on simple principals, yet addresses challenges faced by the system engineers when designing complex data and information infrastructure. The document provides guidance for breaking out various work elements in the overall network architecture design, so that communication systems are conceived and effectively realized regardless of their location, size and local specifics. Although targeted at the Global Airspace System (GAS) and National Airspace System (NAS), this framework can be applied to any network-centric architecture.

Dynamic breaking of a single gold bond

NASA Astrophysics Data System (ADS)

Pobelov, Ilya V.; Lauritzen, Kasper Primdal; Yoshida, Koji; Jensen, Anders; Mészáros, Gábor; Jacobsen, Karsten W.; Strange, Mikkel; Wandlowski, Thomas; Solomon, Gemma C.

2017-07-01

While one might assume that the force to break a chemical bond gives a measure of the bond strength, this intuition is misleading. If the force is loaded slowly, thermal fluctuations may break the bond before it is maximally stretched, and the breaking force will be less than the bond can sustain. Conversely, if the force is loaded rapidly it is more likely that the maximum breaking force is measured. Paradoxically, no clear differences in breaking force were observed in experiments on gold nanowires, despite being conducted under very different conditions. Here we explore the breaking behaviour of a single Au-Au bond and show that the breaking force is dependent on the loading rate. We probe the temperature and structural dependencies of breaking and suggest that the paradox can be explained by fast breaking of atomic wires and slow breaking of point contacts giving very similar breaking forces.

The cellular immune response of Daphnia magna under host-parasite genetic variation and variation in initial dose.

PubMed

Auld, Stuart K J R; Edel, Kai H; Little, Tom J

2012-10-01

In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

The Trail Less Traveled: Individual Decision-Making and Its Effect on Group Behavior

PubMed Central

Lanan, Michele C.; Dornhaus, Anna; Jones, Emily I.; Waser, Andrew; Bronstein, Judith L.

2012-01-01

Social insect colonies are complex systems in which the interactions of many individuals lead to colony-level collective behaviors such as foraging. However, the emergent properties of collective behaviors may not necessarily be adaptive. Here, we examine symmetry breaking, an emergent pattern exhibited by some social insects that can lead colonies to focus their foraging effort on only one of several available food patches. Symmetry breaking has been reported to occur in several ant species. However, it is not clear whether it arises as an unavoidable epiphenomenon of pheromone recruitment, or whether it is an adaptive behavior that can be controlled through modification of the individual behavior of workers. In this paper, we used a simulation model to test how symmetry breaking is affected by the degree of non-linearity of recruitment, the specific mechanism used by individuals to choose between patches, patch size, and forager number. The model shows that foraging intensity on different trails becomes increasingly asymmetric as the recruitment response of individuals varies from linear to highly non-linear, supporting the predictions of previous work. Surprisingly, we also found that the direction of the relationship between forager number (i.e., colony size) and asymmetry varied depending on the specific details of the decision rule used by individuals. Limiting the size of the resource produced a damping effect on asymmetry, but only at high forager numbers. Variation in the rule used by individual ants to choose trails is a likely mechanism that could cause variation among the foraging behaviors of species, and is a behavior upon which selection could act. PMID:23112880

Human Langerhans cells use an IL-15R-α/IL-15/pSTAT5-dependent mechanism to break T-cell tolerance against the self-differentiation tumor antigen WT1.

PubMed

Romano, Emanuela; Cotari, Jesse W; Barreira da Silva, Rosa; Betts, Brian C; Chung, David J; Avogadri, Francesca; Fink, Mitsu J; St Angelo, Erin T; Mehrara, Babak; Heller, Glenn; Münz, Christian; Altan-Bonnet, Gregoire; Young, James W

2012-05-31

Human CD34(+) progenitor-derived Langerhans-type dendritic cells (LCs) are more potent stimulators of T-cell immunity against tumor and viral antigens in vitro than are monocyte-derived DCs (moDCs). The exact mechanisms have remained elusive until now, however. LCs synthesize the highest amounts of IL-15R-α mRNA and protein, which binds IL-15 for presentation to responder lymphocytes, thereby signaling the phosphorylation of signal transducer and activator of transcription 5 (pSTAT5). LCs electroporated with Wilms tumor 1 (WT1) mRNA achieve sufficiently sustained presentation of antigenic peptides, which together with IL-15R-α/IL-15, break tolerance against WT1 by stimulating robust autologous, WT1-specific cytolytic T-lymphocytes (CTLs). These CTLs develop from healthy persons after only 7 days' stimulation without exogenous cytokines and lyse MHC-restricted tumor targets, which include primary WT1(+) leukemic blasts. In contrast, moDCs require exogenous rhuIL-15 to phosphorylate STAT5 and attain stimulatory capacity comparable to LCs. LCs therefore provide a more potent costimulatory cytokine milieu for T-cell activation than do moDCs, thus accounting for their superior stimulation of MHC-restricted Ag-specific CTLs without need for exogenous cytokines. These data support the use of mRNA-electroporated LCs, or moDCs supplemented with exogenous rhuIL-15, as vaccines for cancer immunotherapy to break tolerance against self-differentiation antigens shared by tumors.

Analysis of Heavy Ion-Induced Chromosome Aberrations in Human Fibroblast Cells Using In Situ Hybridization

NASA Technical Reports Server (NTRS)

Wu, Honglu; Durante, Marco; Furusawa, Yoshiya; George, Kerry; Kawata, Tetsuya; Cucinotta, Francis A.

2003-01-01

Confluent human fibroblast cells (AG1522) were irradiated with gamma rays, 490 MeV/nucleon Si, or with Fe ions at either 200 or 500 MeV/nucleon. The cells were allowed to repair at 37 0 C for 24 hours after exposure, and a chemically induced premature chromosome condensation (PCC) technique was used to condense chromosomes in the G2 phase of the cell cycle. Unrejoined chromosomal breaks and complex exchanges were analyzed in the irradiated samples. In order to verify that chromosomal breaks were truly unrejoined, chromosome aberrations were analyzed using a combination of whole chromosome specific probes and probes specific for the telomere region of the chromosome. Results showed that the frequency of unrejoined chromosome breaks was higher after high-LET radiation, and consequently, the ratio of incomplete to complete exchanges increased steadily with LET up to 440 keV/micron, the highest LET value in the present study. For samples exposed to 200 MeV/nucleon Fe ions, chromosome aberrations were analyzed using the multicolor FISH (mFISH) technique that allows identification of both complex and truly incomplete exchanges. Results of the mFISH study showed that 0.7 and 3 Gy dose of the Fe ions produced similar ratios of complex to simple exchanges and incomplete to complete exchanges, values for which were higher than those obtained after a 6 Gy gamma exposure. After 0.7 Gy of Fe ions, most complex aberrations were found to involve three or four chromosomes, indicating the maximum number of chromosome domains traversed by a single Fe ion track. 2

Fluid losses and hydration status of industrial workers under thermal stress working extended shifts

PubMed Central

Brake, D; Bates, G

2003-01-01

Aims: To assess whether workers under significant thermal stress necessarily dehydrated during their exposure and whether "involuntary dehydration" was inevitable, as supported by ISO 9866 and other authorities. Other objectives were to quantify sweat rates against recommended occupational limits, to develop a dehydration protocol to assist with managing heat exposures, and to understand the role of meal breaks on extended shifts in terms of fluid replacement. Methods: A field investigation to examine the fluid consumption, sweat rates, and changes in the hydration state of industrial workers on extended (10, 12, and 12.5 hour) shifts under significant levels of thermal stress (wet bulb globe temperature (WBGT) >28°C) was conducted on 39 male underground miners. Urinary specific gravity was measured before, during, and at the completion of the working shift. Environmental conditions were measured hourly during the shift. Fluid replacement was measured during the working periods and during the meal breaks. Results: Average environmental conditions were severe (WBGT 30.9°C (SD 2.0°C), range 25.7–35.2°C). Fluid intake averaged 0.8 l/h during exposure (SD 0.3 l/h, range 0.3–1.5 l/h). Average urinary specific gravity at start, mid, and end of shift was 1.0251, 1.0248, and 1.0254 respectively; the differences between start and mid shift, mid and end shift, and start and end shift were not significant. However, a majority of workers were coming to work in a moderately hypohydrated state (average urinary specific gravity 1.024 (SD 0.0059)). A combined dehydration and heat illness protocol was developed. Urinary specific gravity limits of 1.022 for start of shift and 1.030 for end of shift were selected; workers exceeding these values were not allowed into the workplace (if the start of shift limit was exceeded) or were retested prior to their next working shift (if the end of shift limit was exceeded). A target of 1.015 as a euhydrated state for start of shift was adopted for workforce education. Conclusions: This study found that "involuntary dehydration" did not occur in well informed workers, which has implications for heat stress standards that do not make provision for full fluid replacement during heat exposure. Fluid replacement during meal breaks was not significantly increased above fluid replacement rates during work time, with implications for the duration and spacing of meal breaks on long shifts. Testing of urinary specific gravity was found to be a good indication of hydration status and a practical method of improving workforce awareness and understanding of this important risk factor. Approximately 10 000 dehydration tests have been conducted under the dehydration protocol in a workforce of 2000 persons exposed to thermal stress and has proved practical and reliable. PMID:12554834

Evidence for broken Galilean invariance at the quantum spin Hall edge

NASA Astrophysics Data System (ADS)

Geissler, Florian; Crépin, François; Trauzettel, Björn

2015-12-01

We study transport properties of the helical edge channels of a quantum spin Hall insulator, in the presence of electron-electron interactions and weak, local Rashba spin-orbit coupling. The combination of the two allows for inelastic backscattering that does not break time-reversal symmetry, resulting in interaction-dependent power-law corrections to the conductance. Here, we use a nonequilibrium Keldysh formalism to describe the situation of a long, one-dimensional edge channel coupled to external reservoirs, where the applied bias is the leading energy scale. By calculating explicitly the corrections to the conductance up to fourth order of the impurity strength, we analyze correlated single- and two-particle backscattering processes on a microscopic level. Interestingly, we show that the modeling of the leads together with the breaking of Galilean invariance has important effects on the transport properties. Such breaking occurs because the Galilean invariance of the bulk spectrum transforms into an emergent Lorentz invariance of the edge spectrum. With this broken Galilean invariance at the quantum spin Hall edge, we find a contribution to single-particle backscattering with a very low power scaling, while in the presence of Galilean invariance the leading contribution will be due to correlated two-particle backscattering only. This difference is further reflected in the different values of the Fano factor of the shot noise, an experimentally observable quantity. The described behavior is specific to the Rashba scatterer and does not occur in the case of backscattering off a time-reversal-breaking, magnetic impurity.

Breaking difficult news in a newborn setting: Down syndrome as a paradigm.

PubMed

Dent, Karin M; Carey, John C

2006-08-15

Breaking the difficult news of an unexpected diagnosis to parents in the newborn setting is a common occurrence in genetic counseling. Many clinical geneticists and genetic counselors have had the challenge of delivering a postnatal diagnosis of Down syndrome to parents of newborns. Down syndrome is a common chromosome condition occurring in approximately 1 in 800 live births. Presenting the diagnosis to families must be accomplished in a supportive, positive, caring, and honest manner. However, there are few scientific data and little instruction in training programs on how best to convey this news in an appropriate manner. Several articles in the literature over the last three decades have proposed various guidelines for the so-called informing interview. Discussions of parents' preferences and experiences in receiving this news have also been documented. Few reports, however, have focused on breaking difficult news of the diagnosis of a genetic condition to parents in a newborn setting in the genetics literature. In this paper, we will review the medical literature on delivering difficult news, specifically focused on that regarding the diagnosis of Down syndrome in the newborn setting. We propose a theoretical framework from which the informing interview can be planned and future outcome data can be measured. In this way, researchers of this theme can investigate the process, including the healthcare professionals' delivery of difficult news and make recommendations for continued improvement of the process. Our model can be generalized to breaking difficult news for a variety of other congenital conditions.

The highest-ranking rooster has priority to announce the break of dawn

PubMed Central

Shimmura, Tsuyoshi; Ohashi, Shosei; Yoshimura, Takashi

2015-01-01

The “cock-a-doodle-doo” crowing of roosters, which symbolizes the break of dawn in many cultures, is controlled by the circadian clock. When one rooster announces the break of dawn, others in the vicinity immediately follow. Chickens are highly social animals, and they develop a linear and fixed hierarchy in small groups. We found that when chickens were housed in small groups, the top-ranking rooster determined the timing of predawn crowing. Specifically, the top-ranking rooster always started to crow first, followed by its subordinates, in descending order of social rank. When the top-ranking rooster was physically removed from a group, the second-ranking rooster initiated crowing. The presence of a dominant rooster significantly reduced the number of predawn crows in subordinates. However, the number of crows induced by external stimuli was independent of social rank, confirming that subordinates have the ability to crow. Although the timing of subordinates’ predawn crowing was strongly dependent on that of the top-ranking rooster, free-running periods of body temperature rhythms differed among individuals, and crowing rhythm did not entrain to a crowing sound stimulus. These results indicate that in a group situation, the top-ranking rooster has priority to announce the break of dawn, and that subordinate roosters are patient enough to wait for the top-ranking rooster’s first crow every morning and thus compromise their circadian clock for social reasons. PMID:26203594

DNA strand-exchange patterns associated with double-strand break-induced and spontaneous mitotic crossovers in Saccharomyces cerevisiae

PubMed Central

2018-01-01

Mitotic recombination can result in loss of heterozygosity and chromosomal rearrangements that shape genome structure and initiate human disease. Engineered double-strand breaks (DSBs) are a potent initiator of recombination, but whether spontaneous events initiate with the breakage of one or both DNA strands remains unclear. In the current study, a crossover (CO)-specific assay was used to compare heteroduplex DNA (hetDNA) profiles, which reflect strand exchange intermediates, associated with DSB-induced versus spontaneous events in yeast. Most DSB-induced CO products had the two-sided hetDNA predicted by the canonical DSB repair model, with a switch in hetDNA position from one product to the other at the position of the break. Approximately 40% of COs, however, had hetDNA on only one side of the initiating break. This anomaly can be explained by a modified model in which there is frequent processing of an early invasion (D-loop) intermediate prior to extension of the invading end. Finally, hetDNA tracts exhibited complexities consistent with frequent expansion of the DSB into a gap, migration of strand-exchange junctions, and template switching during gap-filling reactions. hetDNA patterns in spontaneous COs isolated in either a wild-type background or in a background with elevated levels of reactive oxygen species (tsa1Δ mutant) were similar to those associated with the DSB-induced events, suggesting that DSBs are the major instigator of spontaneous mitotic recombination in yeast. PMID:29579095

Sibling rivalry: competition between Pol X family members in V(D)J recombination and general double strand break repair.

PubMed

Nick McElhinny, Stephanie A; Ramsden, Dale A

2004-08-01

The nonhomologous end-joining pathway is a major means for repairing double-strand breaks (DSBs) in all mitotic cell types. This repair pathway is also the only efficient means for resolving DSB intermediates in V(D)J recombination, a lymphocyte-specific genome rearrangement required for assembly of antigen receptors. A role for polymerases in end-joining has been well established. They are a major factor in determining the character of repair junctions but, in contrast to 'core' end-joining factors, typically appear to have a subtle impact on the efficiency of end-joining. Recent work implicates several members of the Pol X family in end-joining and suggests surprising complexity in the control of how these different polymerases are employed in this pathway.

Repair of DNA damage induced by accelerated heavy ions--a mini review.

PubMed

Okayasu, Ryuichi

2012-03-01

Increasing use of heavy ions for cancer therapy and concerns from exposure to heavy charged particles in space necessitate the study of the basic biological mechanisms associated with exposure to heavy ions. As the most critical damage induced by ionizing radiation is DNA double strand break (DSB), this review focuses on DSBs induced by heavy ions and their repair processes. Compared with X- or gamma-rays, high-linear energy transfer (LET) heavy ion radiation induces more complex DNA damage, categorized into DSBs and non-DSB oxidative clustered DNA lesions (OCDL). This complexity makes the DNA repair process more difficult, partially due to retarded enzymatic activities, leading to increased chromosome aberrations and cell death. In general, the repair process following heavy ion exposure is LET-dependent, but with nonhomologous end joining defective cells, this trend is less emphasized. The variation in cell survival levels throughout the cell cycle is less prominent in cells exposed to high-LET heavy ions when compared with low LET, but this mechanism has not been well understood until recently. Involvement of several DSB repair proteins is suggested to underlie this interesting phenomenon. Recent improvements in radiation-induced foci studies combined with high-LET heavy ion exposure could provide a useful opportunity for more in depth study of DSB repair processes. Accelerated heavy ions have become valuable tools to investigate the molecular mechanisms underlying repair of DNA DSBs, the most crucial form of DNA damage induced by radiation and various chemotherapeutic agents. Copyright © 2011 UICC.

A Preliminary Investigation of Caffeinated Alcohol Use During Spring Break.

PubMed

Linden-Carmichael, Ashley N; Lau-Barraco, Cathy

2016-06-06

Caffeinated alcoholic beverages (e.g., Red Bull and vodka) are popular but associated with negative consequences. CABs may be particularly popular during Spring Break, a potentially risky social event. We aimed to identify the prevalence of Spring Break caffeinated alcohol use, determine how caffeinated alcohol use Spring Break drinking habits differ from usual, and examine the association between Spring Break caffeinated alcohol use and alcohol-related problems. Data were collected from 95 college students during March of 2013 and 2014. Students completed questionnaires of their alcohol and caffeinated alcohol use before and during Spring Break and Spring Break alcohol-related problems. Approximately 54% of students used caffeinated alcohol during Spring Break. Spring Break caffeinated alcohol use was associated with more alcohol-related problems, even after controlling for other alcohol consumed and Spring Break vacation status. Caffeinated alcoholic beverages are commonly consumed during Spring Break and their use uniquely predicted harms. Prevention efforts placed on caffeinated alcoholic beverage users may be helpful in reducing Spring Break-related harms.

Reorganization of Motor Cortex by Vagus Nerve Stimulation Requires Cholinergic Innervation.

PubMed

Hulsey, Daniel R; Hays, Seth A; Khodaparast, Navid; Ruiz, Andrea; Das, Priyanka; Rennaker, Robert L; Kilgard, Michael P

2016-01-01

Vagus nerve stimulation (VNS) paired with forelimb training drives robust, specific reorganization of movement representations in the motor cortex. The mechanisms that underlie VNS-dependent enhancement of map plasticity are largely unknown. The cholinergic nucleus basalis (NB) is a critical substrate in cortical plasticity, and several studies suggest that VNS activates cholinergic circuitry. We examined whether the NB is required for VNS-dependent enhancement of map plasticity in the motor cortex. Rats were trained to perform a lever pressing task and then received injections of the immunotoxin 192-IgG-saporin to selectively lesion cholinergic neurons of the NB. After lesion, rats underwent five days of motor training during which VNS was paired with successful trials. At the conclusion of behavioral training, intracortical microstimulation was used to document movement representations in motor cortex. VNS paired with forelimb training resulted in a substantial increase in the representation of proximal forelimb in rats with an intact NB compared to untrained controls. NB lesions prevent this VNS-dependent increase in proximal forelimb area and result in representations similar to untrained controls. Motor performance was similar between groups, suggesting that differences in forelimb function cannot account for the difference in proximal forelimb representation. Together, these findings indicate that the NB is required for VNS-dependent enhancement of plasticity in the motor cortex and may provide insight into the mechanisms that underlie the benefits of VNS therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

The lifespan-reproduction trade-off under dietary restriction is sex-specific and context-dependent.

PubMed

Adler, Margo I; Cassidy, Elizabeth J; Fricke, Claudia; Bonduriansky, Russell

2013-06-01

Adult dietary restriction (DR) extends lifespan, but the mechanisms that underlie this effect are not well understood. Many DR studies have demonstrated that lifespan extension tends to be accompanied by a reduction in female fecundity - a correlation widely interpreted as evidence that DR triggers an adaptive re - allocation of resources from reproduction to somatic maintenance. Yet, recent evidence suggests that survival and fecundity need not always trade off under DR, calling the re-allocation hypothesis into question. Because the effects of DR on both survival and reproduction have rarely been tested in both sexes, or under a range of ecologically-relevant environments, the generality of this trade-off remains unclear. We examined the effects of DR on survival and reproduction in both sexes and across a range of environments (larval diet quality and adult sex ratio) in the neriid fly Telostylinus angusticollis. We found that the lifespan-reproduction trade-off is both context- and sex-dependent. Although DR extended lifespan in both sexes by 65% and rendered females completely infertile, costs of DR on male fecundity were subtle and evident only in particular environmental combinations. Our findings suggest that a re-allocation of resources may not underlie the lifespan extension response to DR. Instead, full feeding may be associated with increased costs in comparison to DR, such that lifespan extension may be achieved without an increased resource investment to the soma. Copyright © 2013 Elsevier Inc. All rights reserved.

Mental Disorders among Persons with Heart Disease - Results from the World Mental Health Surveys

PubMed Central

Ormel, Johan; Von Korff, Michael; Burger, Huibert; Scott, Kate; Demyttenaere, Koen; Huang, Yue-qin; Posada-Villa, José; Lepine, Jean Pierre; Angermeyer, Matthias C.; Levinson, Daphna; de Girolamo, Giovanni; Kawakami, Norito; Karam, Elie; Medina-Mora, María Elena; Gureje, Oye; Williams, David; Haro, Josep Maria; Bromet, Evelyn J.; Alonso, Jordi; Kessler, Ron

2007-01-01

Objective While in western countries depression and heart disease often co-occur, less is known about the association of anxiety and alcohol use disorders with heart disease and about the cross-cultural consistency of these associations. Consistency across emotional disorders and cultures would suggest that relatively universal mechanisms underlie the association. Method Surveys in 18 random population samples of household-residing adults in 17 countries in Europe, the Americas, the Middle East, Africa, Asia and the South Pacific. Medically recognized heart disease was ascertained by self-report. Mental disorders were assessed with the WMH-CIDI, a fully structured diagnostic interview. Results Specific mood and anxiety disorders occurred among persons with heart disease at higher rates than among persons without heart disease. Adjusted for gender and age, the pooled odds ratios (95% CI) were 2.1 (1.9,2.5) for mood disorders, 2.2 (1.9,2.5) for anxiety disorders, and 1.4 (1.0,1.9) for alcohol abuse/dependence among persons with versus without heart disease. This pattern was similar across countries. Conclusions An excess of anxiety disorders, as well as mood disorders, is found among persons with heart disease. These associations hold across countries despite substantial between-country differences in culture and mental disorder prevalence rates. These results suggest that similar mechanisms underlie the associations and that a broad spectrum of mood-anxiety disorders should be considered in research on the comorbidity of mental disorders and heart disease. PMID:17591509

Quantitative trait loci for response to ethanol in an intercontinental set of recombinant inbred lines of Drosophila melanogaster.

PubMed

Defays, Raquel; Bertoli, Carlos Ignacio

2012-12-01

Alcohol, a drug widely abused, impacts the central nervous system functioning of diverse organisms. The behavioral responses to acute alcohol exposure are remarkably similar among humans and fruit flies. In its natural environment, rich in fermentation products, the fruit fly Drosophila melanogaster encounters relatively high levels of ethanol. The effects of ethanol and its metabolites on Drosophila have been studied for decades, as a model for adaptive evolution. Although extensive work has been done for elucidating patterns of genetic variation, substantially less is known about the genomic regions or genes that underlie the genetic variation of this important trait. To identify regions containing genes involved in the responses to ethanol, we used a mapping population of recombinant inbred (RIL) lines to map quantitative trait loci (QTL) that affect variation in resistance and recovery from ethanol sedation in adults and ethanol resistance in larvae. We mapped fourteen QTL affecting the response to ethanol on the three chromosomes. Seven of the QTL influence the resistance to ethanol in adults, two QTL are related to ethanol-coma recovery in adults and five affect the survival to ethanol in larvae. Most of the QTL were trait specific, suggesting that overlapping but generally unique genetic architectures underlie each trait. Each QTL explained up to 16.8% of the genetic variance among lines. Potential candidate loci contained within our QTL regions were identified and analyzed. Copyright © 2012 Elsevier Inc. All rights reserved.

A twin study of the genetics of fear conditioning.

PubMed

Hettema, John M; Annas, Peter; Neale, Michael C; Kendler, Kenneth S; Fredrikson, Mats

2003-07-01

Fear conditioning is a traditional model for the acquisition of fears and phobias. Studies of the genetic architecture of fear conditioning may inform gene-finding strategies for anxiety disorders. The objective of this study was to determine the genetic and environmental sources of individual differences in fear conditioning by means of a twin sample. Classic fear conditioning data were experimentally obtained from 173 same-sex twin pairs (90 monozygotic and 83 dizygotic). Sequences of evolutionary fear-relevant (snakes and spiders) and fear-irrelevant (circles and triangles) pictorial stimuli served as conditioned stimuli paired with a mild electric shock serving as the unconditioned stimulus. The outcome measure was the electrodermal skin conductance response. We applied structural equation modeling methods to the 3 conditioning phases of habituation, acquisition, and extinction to determine the extent to which genetic and environmental factors underlie individual variation in associative and nonassociative learning. All components of the fear conditioning process in humans demonstrated moderate heritability, in the range of 35% to 45%. Best-fitting multivariate models suggest that 2 sets of genes may underlie the trait of fear conditioning: one that most strongly affects nonassociative processes of habituation that also is shared with acquisition and extinction, and a second that appears related to associative fear conditioning processes. In addition, these data provide tentative evidence of differences in heritability based on the fear relevance of the stimuli. Genes represent a significant source of individual variation in the habituation, acquisition, and extinction of fears, and genetic effects specific to fear conditioning are involved.

Enamel Protein Regulation and Dental and Periodontal Physiopathology in Msx2 Mutant Mice

PubMed Central

Molla, Muriel; Descroix, Vianney; Aïoub, Muhanad; Simon, Stéphane; Castañeda, Beatriz; Hotton, Dominique; Bolaños, Alba; Simon, Yohann; Lezot, Frédéric; Goubin, Gérard; Berdal, Ariane

2010-01-01

Signaling pathways that underlie postnatal dental and periodontal physiopathology are less studied than those of early tooth development. Members of the muscle segment homeobox gene (Msx) family encode homeoproteins that show functional redundancy during development and are known to be involved in epithelial-mesenchymal interactions that lead to crown morphogenesis and ameloblast cell differentiation. This study analyzed the MSX2 protein during mouse postnatal growth as well as in the adult. The analysis focused on enamel and periodontal defects and enamel proteins in Msx2-null mutant mice. In the epithelial lifecycle, the levels of MSX2 expression and enamel protein secretion were inversely related. Msx2+/− mice showed increased amelogenin expression, enamel thickness, and rod size. Msx2−/− mice displayed compound phenotypic characteristics of enamel defects, related to both enamel-specific gene mutations (amelogenin and enamelin) in isolated amelogenesis imperfecta, and cell-cell junction elements (laminin 5 and cytokeratin 5) in other syndromes. These effects were also related to ameloblast disappearance, which differed between incisors and molars. In Msx2−/− roots, Malassez cells formed giant islands that overexpressed amelogenin and ameloblastin that grew over months. Aberrant expression of enamel proteins is proposed to underlie the regional osteopetrosis and hyperproduction of cellular cementum. These enamel and periodontal phenotypes of Msx2 mutants constitute the first case report of structural and signaling defects associated with enamel protein overexpression in a postnatal context. PMID:20934968

Characterization of glioma stem cells through multiple stem cell markers and their specific sensitization to double-strand break-inducing agents by pharmacological inhibition of ataxia telangiectasia mutated protein.

PubMed

Raso, Alessandro; Vecchio, Donatella; Cappelli, Enrico; Ropolo, Monica; Poggi, Alessandro; Nozza, Paolo; Biassoni, Roberto; Mascelli, Samantha; Capra, Valeria; Kalfas, Fotios; Severi, Paolo; Frosina, Guido

2012-09-01

Previous studies have shown that tumor-driving glioma stem cells (GSC) may promote radio-resistance by constitutive activation of the DNA damage response started by the ataxia telangiectasia mutated (ATM) protein. We have investigated whether GSC may be specifically sensitized to ionizing radiation by inhibiting the DNA damage response. Two grade IV glioma cell lines (BORRU and DR177) were characterized for a number of immunocytochemical, karyotypic, proliferative and differentiative parameters. In particular, the expression of a panel of nine stem cell markers was quantified by reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. Overall, BORRU and DR177 displayed pronounced and poor stem phenotypes, respectively. In order to improve the therapeutic efficacy of radiation on GSC, the cells were preincubated with a nontoxic concentration of the ATM inhibitors KU-55933 and KU-60019 and then irradiated. BORRU cells were sensitized to radiation and radio-mimetic chemicals by ATM inhibitors whereas DR177 were protected under the same conditions. No sensitization was observed after cell differentiation or to drugs unable to induce double-strand breaks (DSB), indicating that ATM inhibitors specifically sensitize glioma cells possessing stem phenotype to DSB-inducing agents. In conclusion, pharmacological inhibition of ATM may specifically sensitize GSC to DSB-inducing agents while sparing nonstem cells. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

Intestinal Master Transcription Factor CDX2 Controls Chromatin Access for Partner Transcription Factor Binding

PubMed Central

Verzi, Michael P.; Shin, Hyunjin; San Roman, Adrianna K.

2013-01-01

Tissue-specific gene expression requires modulation of nucleosomes, allowing transcription factors to occupy cis elements that are accessible only in selected tissues. Master transcription factors control cell-specific genes and define cellular identities, but it is unclear if they possess special abilities to regulate cell-specific chromatin and if such abilities might underlie lineage determination and maintenance. One prevailing view is that several transcription factors enable chromatin access in combination. The homeodomain protein CDX2 specifies the embryonic intestinal epithelium, through unknown mechanisms, and partners with transcription factors such as HNF4A in the adult intestine. We examined enhancer chromatin and gene expression following Cdx2 or Hnf4a excision in mouse intestines. HNF4A loss did not affect CDX2 binding or chromatin, whereas CDX2 depletion modified chromatin significantly at CDX2-bound enhancers, disrupted HNF4A occupancy, and abrogated expression of neighboring genes. Thus, CDX2 maintains transcription-permissive chromatin, illustrating a powerful and dominant effect on enhancer configuration in an adult tissue. Similar, hierarchical control of cell-specific chromatin states is probably a general property of master transcription factors. PMID:23129810

The crown-of-thorns starfish genome as a guide for biocontrol of this coral reef pest.

PubMed

Hall, Michael R; Kocot, Kevin M; Baughman, Kenneth W; Fernandez-Valverde, Selene L; Gauthier, Marie E A; Hatleberg, William L; Krishnan, Arunkumar; McDougall, Carmel; Motti, Cherie A; Shoguchi, Eiichi; Wang, Tianfang; Xiang, Xueyan; Zhao, Min; Bose, Utpal; Shinzato, Chuya; Hisata, Kanako; Fujie, Manabu; Kanda, Miyuki; Cummins, Scott F; Satoh, Noriyuki; Degnan, Sandie M; Degnan, Bernard M

2017-04-05

The crown-of-thorns starfish (COTS, the Acanthaster planci species group) is a highly fecund predator of reef-building corals throughout the Indo-Pacific region. COTS population outbreaks cause substantial loss of coral cover, diminishing the integrity and resilience of reef ecosystems. Here we sequenced genomes of COTS from the Great Barrier Reef, Australia and Okinawa, Japan to identify gene products that underlie species-specific communication and could potentially be used in biocontrol strategies. We focused on water-borne chemical plumes released from aggregating COTS, which make the normally sedentary starfish become highly active. Peptide sequences detected in these plumes by mass spectrometry are encoded in the COTS genome and expressed in external tissues. The exoproteome released by aggregating COTS consists largely of signalling factors and hydrolytic enzymes, and includes an expanded and rapidly evolving set of starfish-specific ependymin-related proteins. These secreted proteins may be detected by members of a large family of olfactory-receptor-like G-protein-coupled receptors that are expressed externally, sometimes in a sex-specific manner. This study provides insights into COTS-specific communication that may guide the generation of peptide mimetics for use on reefs with COTS outbreaks.

Classification of Genes and Putative Biomarker Identification Using Distribution Metrics on Expression Profiles

PubMed Central

Huang, Hung-Chung; Jupiter, Daniel; VanBuren, Vincent

2010-01-01

Background Identification of genes with switch-like properties will facilitate discovery of regulatory mechanisms that underlie these properties, and will provide knowledge for the appropriate application of Boolean networks in gene regulatory models. As switch-like behavior is likely associated with tissue-specific expression, these gene products are expected to be plausible candidates as tissue-specific biomarkers. Methodology/Principal Findings In a systematic classification of genes and search for biomarkers, gene expression profiles (GEPs) of more than 16,000 genes from 2,145 mouse array samples were analyzed. Four distribution metrics (mean, standard deviation, kurtosis and skewness) were used to classify GEPs into four categories: predominantly-off, predominantly-on, graded (rheostatic), and switch-like genes. The arrays under study were also grouped and examined by tissue type. For example, arrays were categorized as ‘brain group’ and ‘non-brain group’; the Kolmogorov-Smirnov distance and Pearson correlation coefficient were then used to compare GEPs between brain and non-brain for each gene. We were thus able to identify tissue-specific biomarker candidate genes. Conclusions/Significance The methodology employed here may be used to facilitate disease-specific biomarker discovery. PMID:20140228

Allele Mining in Barley Genetic Resources Reveals Genes of Race-Non-Specific Powdery Mildew Resistance

PubMed Central

Spies, Annika; Korzun, Viktor; Bayles, Rosemary; Rajaraman, Jeyaraman; Himmelbach, Axel; Hedley, Pete E.; Schweizer, Patrick

2012-01-01

Race-non-specific, or quantitative, pathogen resistance is of high importance to plant breeders due to its expected durability. However, it is usually controlled by multiple quantitative trait loci (QTL) and therefore difficult to handle in practice. Knowing the genes that underlie race-non-specific resistance (NR) would allow its exploitation in a more targeted manner. Here, we performed an association-genetic study in a customized worldwide collection of spring barley accessions for candidate genes of race-NR to the powdery mildew fungus Blumeria graminis f. sp. hordei (Bgh) and combined data with results from QTL mapping as well as functional-genomics approaches. This led to the identification of 11 associated genes with converging evidence for an important role in race-NR in the presence of the Mlo gene for basal susceptibility. Outstanding in this respect was the gene encoding the transcription factor WRKY2. The results suggest that unlocking plant genetic resources and integrating functional-genomic with genetic approaches can accelerate the discovery of genes underlying race-NR in barley and other crop plants. PMID:22629270

Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio

PubMed Central

Weidmann, Chase A; Qiu, Chen; Arvola, René M; Lou, Tzu-Fang; Killingsworth, Jordan; Campbell, Zachary T; Tanaka Hall, Traci M; Goldstrohm, Aaron C

2016-01-01

Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAs that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics. DOI: http://dx.doi.org/10.7554/eLife.17096.001 PMID:27482653

Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio

DOE PAGES

Weidmann, Chase A.; Qiu, Chen; Arvola, René M.; ...

2016-08-02

Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAsmore » that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.« less

An electrostatic selection mechanism controls sequential kinase signaling downstream of the T cell receptor

PubMed Central

Shah, Neel H; Wang, Qi; Yan, Qingrong; Karandur, Deepti; Kadlecek, Theresa A; Fallahee, Ian R; Russ, William P; Ranganathan, Rama; Weiss, Arthur; Kuriyan, John

2016-01-01

The sequence of events that initiates T cell signaling is dictated by the specificities and order of activation of the tyrosine kinases that signal downstream of the T cell receptor. Using a platform that combines exhaustive point-mutagenesis of peptide substrates, bacterial surface-display, cell sorting, and deep sequencing, we have defined the specificities of the first two kinases in this pathway, Lck and ZAP-70, for the T cell receptor ζ chain and the scaffold proteins LAT and SLP-76. We find that ZAP-70 selects its substrates by utilizing an electrostatic mechanism that excludes substrates with positively-charged residues and favors LAT and SLP-76 phosphosites that are surrounded by negatively-charged residues. This mechanism prevents ZAP-70 from phosphorylating its own activation loop, thereby enforcing its strict dependence on Lck for activation. The sequence features in ZAP-70, LAT, and SLP-76 that underlie electrostatic selectivity likely contribute to the specific response of T cells to foreign antigens. DOI: http://dx.doi.org/10.7554/eLife.20105.001 PMID:27700984

Regulation of hippocampus-dependent memory by the zinc finger protein Zbtb20 in mature CA1 neurons.

PubMed

Ren, Anjing; Zhang, Huan; Xie, Zhifang; Ma, Xianhua; Ji, Wenli; He, David Z Z; Yuan, Wenjun; Ding, Yu-Qiang; Zhang, Xiao-Hui; Zhang, Weiping J

2012-10-01

The mammalian hippocampus harbours neural circuitry that is crucial for associative learning and memory. The mechanisms that underlie the development and regulation of this complex circuitry are not fully understood. Our previous study established an essential role for the zinc finger protein Zbtb20 in the specification of CA1 field identity in the developing hippocampus. Here, we show that conditionally deleting Zbtb20 specifically in mature CA1 pyramidal neurons impaired hippocampus-dependent memory formation, without affecting hippocampal architecture or the survival, identity and basal excitatory synaptic activity of CA1 pyramidal neurons. We demonstrate that mature CA1-specific Zbtb20 knockout mice exhibited reductions in long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated excitatory post-synaptic currents. Furthermore, we show that activity-induced phosphorylation of ERK and CREB is impaired in the hippocampal CA1 of Zbtb20 mutant mice. Collectively, these results indicate that Zbtb20 in mature CA1 plays an important role in LTP and memory by regulating NMDAR activity, and activation of ERK and CREB.

Drosophila Nanos acts as a molecular clamp that modulates the RNA-binding and repression activities of Pumilio

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weidmann, Chase A.; Qiu, Chen; Arvola, René M.

Collaboration among the multitude of RNA-binding proteins (RBPs) is ubiquitous, yet our understanding of these key regulatory complexes has been limited to single RBPs. We investigated combinatorial translational regulation by Drosophila Pumilio (Pum) and Nanos (Nos), which control development, fertility, and neuronal functions. Our results show how the specificity of one RBP (Pum) is modulated by cooperative RNA recognition with a second RBP (Nos) to synergistically repress mRNAs. Crystal structures of Nos-Pum-RNA complexes reveal that Nos embraces Pum and RNA, contributes sequence-specific contacts, and increases Pum RNA-binding affinity. Nos shifts the recognition sequence and promotes repression complex formation on mRNAsmore » that are not stably bound by Pum alone, explaining the preponderance of sub-optimal Pum sites regulated in vivo. Our results illuminate the molecular mechanism of a regulatory switch controlling crucial gene expression programs, and provide a framework for understanding how the partnering of RBPs evokes changes in binding specificity that underlie regulatory network dynamics.« less

Phospho-selective mechanisms of arrestin conformations and functions revealed by unnatural amino acid incorporation and 19F-NMR

PubMed Central

Yang, Fan; Yu, Xiao; Liu, Chuan; Qu, Chang-Xiu; Gong, Zheng; Liu, Hong-Da; Li, Fa-Hui; Wang, Hong-Mei; He, Dong-Fang; Yi, Fan; Song, Chen; Tian, Chang-Lin; Xiao, Kun-Hong; Wang, Jiang-Yun; Sun, Jin-Peng

2015-01-01

Specific arrestin conformations are coupled to distinct downstream effectors, which underlie the functions of many G-protein-coupled receptors (GPCRs). Here, using unnatural amino acid incorporation and fluorine-19 nuclear magnetic resonance (19F-NMR) spectroscopy, we demonstrate that distinct receptor phospho-barcodes are translated to specific β-arrestin-1 conformations and direct selective signalling. With its phosphate-binding concave surface, β-arrestin-1 ‘reads' the message in the receptor phospho-C-tails and distinct phospho-interaction patterns are revealed by 19F-NMR. Whereas all functional phosphopeptides interact with a common phosphate binding site and induce the movements of finger and middle loops, different phospho-interaction patterns induce distinct structural states of β-arrestin-1 that are coupled to distinct arrestin functions. Only clathrin recognizes and stabilizes GRK2-specific β-arrestin-1 conformations. The identified receptor-phospho-selective mechanism for arrestin conformation and the spacing of the multiple phosphate-binding sites in the arrestin enable arrestin to recognize plethora phosphorylation states of numerous GPCRs, contributing to the functional diversity of receptors. PMID:26347956

The Control of the Specificity of CD4 T Cell Responses: Thresholds, Breakpoints, and Ceilings

PubMed Central

Sant, Andrea J.; Chaves, Francisco A.; Leddon, Scott A.; Tung, Jacqueline

2013-01-01

It has been known for over 25 years that CD4 T cell responses are restricted to a finite number of peptide epitopes within pathogens or protein vaccines. These selected peptide epitopes are termed “immunodominant.” Other peptides within the antigen that can bind to host MHC molecules and recruit CD4 T cells as single peptides are termed “cryptic” because they fail to induce responses when expressed in complex proteins or when in competition with other peptides during the immune response. In the last decade, our laboratory has evaluated the mechanisms that underlie the preferential specificity of CD4 T cells and have discovered that both intracellular events within antigen presenting cells, particular selective DM editing, and intercellular regulatory pathways, involving IFN-γ, indoleamine 2,3-dioxygenase, and regulatory T cells, play a role in selecting the final peptide specificity of CD4 T cells. In this review, we summarize our findings, discuss the implications of this work on responses to pathogens and vaccines and speculate on the logic of these regulatory events. PMID:24167504

Beyond Columnar Organization: Cell Type- and Target Layer-Specific Principles of Horizontal Axon Projection Patterns in Rat Vibrissal Cortex

PubMed Central

Narayanan, Rajeevan T.; Egger, Robert; Johnson, Andrew S.; Mansvelder, Huibert D.; Sakmann, Bert; de Kock, Christiaan P.J.; Oberlaender, Marcel

2015-01-01

Vertical thalamocortical afferents give rise to the elementary functional units of sensory cortex, cortical columns. Principles that underlie communication between columns remain however unknown. Here we unravel these by reconstructing in vivo-labeled neurons from all excitatory cell types in the vibrissal part of rat primary somatosensory cortex (vS1). Integrating the morphologies into an exact 3D model of vS1 revealed that the majority of intracortical (IC) axons project far beyond the borders of the principal column. We defined the corresponding innervation volume as the IC-unit. Deconstructing this structural cortical unit into its cell type-specific components, we found asymmetric projections that innervate columns of either the same whisker row or arc, and which subdivide vS1 into 2 orthogonal [supra-]granular and infragranular strata. We show that such organization could be most effective for encoding multi whisker inputs. Communication between columns is thus organized by multiple highly specific horizontal projection patterns, rendering IC-units as the primary structural entities for processing complex sensory stimuli. PMID:25838038

Idiotypic Cascades in Cancer Patients Treated with Monoclonal Antibody CO17-1A

NASA Astrophysics Data System (ADS)

Wettendorff, Martine; Iliopoulos, Dimitrios; Tempero, Margaret; Kay, David; Defreitas, Elaine; Koprowski, Hilary; Herlyn, Dorothee

1989-05-01

We have previously shown that gastrointestinal cancer patients treated with monoclonal antibody CO17-1A (Ab1) developed anti-idiotypic antibodies (Ab2) to the Ab1. We now demonstrate that patients produce anti-anti-idiotypic antibodies (Ab3) to their autologous Ab2. Ab3 were demonstrated in culture supernatants of peripheral blood mononuclear cells from five Ab1-treated patients after stimulation of the cells with heterologous Ab2 that functionally mimicked the tumor antigen (Ag) defined by Ab1 and immunologically cross reacted with the patients' Ab2. Ab3 shared idiotopes with Ab1 and were Ab1-like in their binding specificities to tumor cells, Ag, and Ab2. Such antibodies were also elicited by stimulating cells with Ag. However, they were not produced by stimulating posttreatment mononuclear cells with control proteins or by stimulating pretreatment cells with either Ag or Ab2. Our results demonstrate idiotypic cascades in cancer patients treated with monoclonal antibody. Ag-specific Ab3 responses may underlie delayed clinical responses often observed in cancer patients treated with monoclonal antibodies of various specificities.

Breaking of axial symmetry in excited heavy nuclei as identified in giant dipole resonance data

DOE PAGES

Grosse, E.; Junghans, A. R.; Massarczyk, R.

2017-11-28

Here, a recent theoretical prediction of a breaking of axial symmetry in quasi all heavy nuclei is confronted to a new critical analysis of photon strength functions of nuclei in the valley of stability. For the photon strength in the isovector giant dipole resonance (IVGDR) regime a parameterization of GDR shapes by the sum of three Lorentzians (TLO) is extrapolated to energies below and above the IVGDR. The impact of non-GDR modes adding to the low energy slope of photon strength is discussed including recent data on photon scattering and other radiative processes. These are shown to be concentrated inmore » energy regions where various model calculations predict intermediate collective strength; thus they are obviously separate from the IVGDR tail. The triple Lorentzian (TLO) ansatz for giant dipole resonances is normalized in accordance to the dipole sum rule. The nuclear droplet model with surface dissipation accounts well for positions and widths without local, nuclide specific, parameters. Very few and only global parameters are needed when a breaking of axial symmetry already in the valley of stability is admitted and hence a reliable prediction for electric dipole strength functions also outside of it is expected.« less

Non-abelian vector boson dark matter, its unified route and signatures at the LHC

NASA Astrophysics Data System (ADS)

Barman, Basabendu; Bhattacharya, Subhaditya; Patra, Sunando Kumar; Chakrabortty, Joydeep

2017-12-01

Vector boson dark matter (DM) appears in SU(2)N extension (N stands for neutral) of Standard Model (SM) where an additional global U(1)P symmetry is assumed and results in a generalized lepton number defined as: L=P+T3N. Breaking of U(1)P leads to the breaking of L to (‑1)L, thus stabilizing DM through modified R=(‑1)3B+L+2J. This model, already discussed in literature, offers several novel features to elaborate upon. For example, t-channel annihilation and dominant s-channel direct search, along with co-annihilation, helps the DM to evade stringent direct search bounds from LUX and XENON1T after satisfying relic density constraints. On the other hand, the exotic particles of the model can be produced at the Large Hadron Collider (LHC) yielding multilepton final states. Hadronically quiet four lepton signal with large missing energy, in specific, is shown to provide a smoking gun signature of such a framework. We study the details of E(6) → SM SU(2)N breaking patterns (through D-parity odd/even cases) which yield important phenomenological consequences.

Classification of NLO operators for composite Higgs models

NASA Astrophysics Data System (ADS)

Alanne, Tommi; Bizot, Nicolas; Cacciapaglia, Giacomo; Sannino, Francesco

2018-04-01

We provide a general classification of template operators, up to next-to-leading order, that appear in chiral perturbation theories based on the two flavor patterns of spontaneous symmetry breaking SU (NF)/Sp (NF) and SU (NF)/SO (NF). All possible explicit-breaking sources parametrized by spurions transforming in the fundamental and in the two-index representations of the flavor symmetry are included. While our general framework can be applied to any model of strong dynamics, we specialize to composite-Higgs models, where the main explicit breaking sources are a current mass, the gauging of flavor symmetries, and the Yukawa couplings (for the top). For the top, we consider both bilinear couplings and linear ones à la partial compositeness. Our templates provide a basis for lattice calculations in specific models. As a special example, we consider the SU (4 )/Sp (4 )≅SO (6 )/SO (5 ) pattern which corresponds to the minimal fundamental composite-Higgs model. We further revisit issues related to the misalignment of the vacuum. In particular, we shed light on the physical properties of the singlet η , showing that it cannot develop a vacuum expectation value without explicit C P violation in the underlying theory.

Breaking of axial symmetry in excited heavy nuclei as identified in giant dipole resonance data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grosse, E.; Junghans, A. R.; Massarczyk, R.

Here, a recent theoretical prediction of a breaking of axial symmetry in quasi all heavy nuclei is confronted to a new critical analysis of photon strength functions of nuclei in the valley of stability. For the photon strength in the isovector giant dipole resonance (IVGDR) regime a parameterization of GDR shapes by the sum of three Lorentzians (TLO) is extrapolated to energies below and above the IVGDR. The impact of non-GDR modes adding to the low energy slope of photon strength is discussed including recent data on photon scattering and other radiative processes. These are shown to be concentrated inmore » energy regions where various model calculations predict intermediate collective strength; thus they are obviously separate from the IVGDR tail. The triple Lorentzian (TLO) ansatz for giant dipole resonances is normalized in accordance to the dipole sum rule. The nuclear droplet model with surface dissipation accounts well for positions and widths without local, nuclide specific, parameters. Very few and only global parameters are needed when a breaking of axial symmetry already in the valley of stability is admitted and hence a reliable prediction for electric dipole strength functions also outside of it is expected.« less

UT simulation using a fully automated 3D hybrid model: Application to planar backwall breaking defects inspection

NASA Astrophysics Data System (ADS)

Imperiale, Alexandre; Chatillon, Sylvain; Darmon, Michel; Leymarie, Nicolas; Demaldent, Edouard

2018-04-01

The high frequency models gathered in the CIVA software allow fast computations and provide satisfactory quantitative predictions in a wide range of situations. However, the domain of validity of these models is limited since they do not accurately predict the ultrasound response in configurations involving subwavelength complex phenomena. In addition, when modelling backwall breaking defects inspection, an important challenge remains to capture the propagation of the creeping waves that are generated at the critical angle. Hybrid models combining numerical and asymptotic methods have already been shown to be an effective strategy to overcome these limitations in 2D [1]. However, 3D simulations remain a crucial issue for industrial applications because of the computational cost of the numerical solver. A dedicated three dimensional high order finite element model combined with a domain decomposition method has been recently proposed to tackle 3D limitations [2]. In this communication, we will focus on the specific case of planar backwall breaking defects, with an adapted coupling strategy in order to efficiently model the propagation of creeping waves. Numerical and experimental validations will be proposed on various configurations.

Spin rotational symmetry breaking by orbital current patterns in two-leg Cu-O Hubbard ladders

NASA Astrophysics Data System (ADS)

Chudzinski, Piotr; Gabay, Marc; Giamarchi, Thierry

2010-03-01

In the weak-coupling limit, we study, as a function of doping, two-leg ladders with a unit cell containing both Cu and O atoms. For purely repulsive interactions, using bosonization and a novel RG scheme, we find that in a broad region of the phase diagram, the ground state consists of a pattern of orbital currents (OCP) defined on the top of an incommensurate density wave. The internal symmetry of the OCP is specific for the ladder structure, different than the ones suggested up to now for 2D cuprates. We focus on this OCP and look for measurable signals of its existence: we compute magnetic fields induced within the ladder and we check what kind of changes in the phase diagram one may expect due to SU(2) spin-rotational symmetry breaking. We also investigate a single impurity problem (incl. OCP): we discuss if Kondo physics is at play, and make qualitative predictions about the nature of impurity backscattering. This enables us to show the influence of SU(2) symmetry breaking on conductivity. We estimate the value of gap opened due to the OCP, give analytic expressions for correlation functions and discuss magnetic properties of a new phase.

Regression among Students with Autism Spectrum Disorders: An Examination of Extended School Year Programming

ERIC Educational Resources Information Center

Cross, Emily R.

2013-01-01

The effects of long school breaks, such as summer vacation, on students' achievement has been an area of interest among educators and researchers for many years (e.g. Austin, Rogers & Walbesser, 1972; Ballinger, 1987, 1988; Borman, Benson & Overman, 2005; White, 1906). Research specific to children and youth with disabilities and the…

Breaking Ground: Improving Undergraduate Engineering Projects through Flipped Teaching of Literature Search Techniques

ERIC Educational Resources Information Center

Maddison, Tasha; Beneteau, Donna; Sokoloski, Brandy

2014-01-01

This case study describes the use of flipped teaching for information literacy instruction in a new course, "Drill, Blast, and Excavate GeoE 498," within the mining option for geological engineering (GeoE) students. These students will enter the mining industry with less discipline-specific knowledge than a student that graduated with a…

Off-road vehicle trends

Treesearch

Garrell E. Nicholes

1980-01-01

Today I would like to start this part of my program by generally describing the vehicles, the users, and the current problems. Later on I will break out specifically motorcycles and snowmobiles to discuss. When I was asked, approximately a year ago, to fill this assignment, I began by telephoning those I knew in public and private ORV management positions. I sent...

The Good Writing Guide for Education Students. Second Edition

ERIC Educational Resources Information Center

Wyse, Dominic

2007-01-01

Whether you are returning to studying after a break, or need help adjusting your writing skills to meet the needs of your education course, this practical, down-to-earth guide will help you improve your literacy skills. Aimed specifically at students in education courses, this book uses examples of students' work to highlight common problems, and…

Somatic recombination in wheat stem rust leads to virulence for Ug99-effective SR50 resistance

USDA-ARS?s Scientific Manuscript database

Race-specific resistance genes protect much of the global wheat crop from stem rust disease caused by Puccinia graminis f. sp. tritici (Pgt), but often break down due to evolution of new virulent pathogen races. To understand the molecular mechanisms of virulence evolution in Pgt we identified the p...

Extensiveness--Accuracy of Parent Information about Virginia Beach 45-15 Pilot Program.

ERIC Educational Resources Information Center

Schlechty Associates, Chapel Hill, NC.

A preliminary analysis of parent responses to questions related to factual information about the Virginia Beach 45-15 pilot elementary school program, where students attend classes 45 days and break 15 days year round, is provided. Specifically, the information component of the Virginia Beach 45-15 Pilot Project Questionnaire, which consists of…

TACSAT-4 Early Flight Operations Including Lessons From Integration, Test, and Launch Processing

DTIC Science & Technology

2012-08-01

Healy used TacSat-4 as it returned from the Bering Sea from its ice breaking mission with the Russian tanker Renda to deliver emergency fuel supplies to...required extra design and verification work for the electrical power system, but it provided real benefits at the launch range. Specifically, it eliminated

Power Factors that Define Gender Inequity within the Missouri Public School Superintendency

ERIC Educational Resources Information Center

Alexander, Kristina; Grispino, Frank D.; Messner, Phillip E.

2004-01-01

Although women have access to the superintendency power position, evidence has shown that women have not been able to consistently break the glass ceiling. A review of related literature failed to identify specific and practical employment factors that must be resolved or overcome if women are to reach power parity in Missouri. This study was…

Learning Together: How Families Responded to Education Incentives in New York City's Conditional Cash Transfer Program

ERIC Educational Resources Information Center

Greenberg, David; Dechausay, Nadine; Fraker, Carolyn

2011-01-01

In 2007, New York City's Center for Economic Opportunity launched Opportunity NYC-Family Rewards, an experimental, privately funded, conditional cash transfer (CCT) program to help families break the cycle of poverty. Family Rewards provided payments to low-income families in six of the city's poorest communities for achieving specific goals…

In Search of a Break in the Clouds: An Ethnographic Study of Academic and Student Affairs Cultures

ERIC Educational Resources Information Center

Arcelus, Victor J.

2008-01-01

This study investigates the cultures of the academic and student affairs divisions within one selective residential liberal arts institution. Specifically, the study investigates how faculty and student affairs personnel perceive their own and each other's roles as educators on the campus and how these perceptions influence the potential for…

Multi-Species Genome Comparison Sheds New Light on Evolutionary Processes, Cancer Mutations

ERIC Educational Resources Information Center

Journal of College Science Teaching, 2005

2005-01-01

An international team that includes researchers from the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), has discovered that mammalian chromosomes have evolved by breaking at specific sites rather than randomly as long thought--and that many of the breakage hot spots are also involved in human…

Ripples and Breaks: Reflecting on Learning Ecologies in Career and Technical Education

ERIC Educational Resources Information Center

Jocson, Korina M.

2016-01-01

In this paper, the author reflects on a year-long ethnography to point out contextual factors situated in career and technical education (CTE) and specifically how a CTE teacher and a university researcher shaped learning opportunities to support students' interests in the arts, technology, and multimedia communications. The discussion arched by a…

Dismantling the Context and Breaking Free from Contextual Oppositions: How Teacher Education Programs Can Combat Homophobia

ERIC Educational Resources Information Center

Jones, Joseph R.

2012-01-01

In exploring homophobia in schools, the author discusses a qualitative research study conducted with a group of teachers from New York State. The article examines how the group of teachers (participating in professional development program) discusses their perceptions of homophobia in their classrooms and schools. Specifically, the teachers…

Meta-analysis of the association between rumination and reduced autobiographical memory specificity.

PubMed

Chiu, Connie P Y; Griffith, James W; Lenaert, Bert; Raes, Filip; Hermans, Dirk; Barry, Tom J

2018-05-16

The CaRFAX model, proposed by Williams J. M. G. (2006. Capture and rumination, functional avoidance, and executive control (CaRFAX): Three processes that underlie overgeneral memory. Cognition and Emotion, 20, 548-568. doi: 10.1080/02699930500450465 ; Williams, J. M. G., Barnhofer, T., Crane, C., Herman, D., Raes, F., Watkins, E., & Dalgleish, T. (2007). Autobiographical memory specificity and emotional disorder. Psychological Bulletin, 133(1), 122-148. doi: 10.1037/0033-2909.133.1.122 ) posits that reduced autobiographical memory specificity, a key factor associated with the emergence and maintenance of emotional disorders, may result from heightened rumination. We provide the first meta-analysis of the relation between autobiographical memory specificity and trait rumination. PsycINFO, PsycARTICLES and MEDLINE databases were searched and the following were extracted: the correlation between the number of specific memories recalled in the Autobiographical Memory Test and self-reported trait rumination scores, and its sub-factors - brooding and reflection. The pooled effect size for the correlation between memory specificity and trait rumination was small (d = -.05) and did not differ significantly from zero (p = .09). The effect sizes for the correlation with brooding and reflection were not significantly different from zero. There is limited support for the association between trait rumination and memory specificity suggested in CaRFAX.

Break the "wall" and become creative: Enacting embodied metaphors in virtual reality.

PubMed

Wang, Xinyue; Lu, Kelong; Runco, Mark A; Hao, Ning

2018-07-01

This study investigated whether the experience of "breaking the walls", the embodiment of the metaphor "breaking the rules", could enhance creative performance. The virtual reality technology was used to simulate the scenario where participants could "break the walls" while walking in a corridor. Participants were asked to solve the creativity-demanding problems (ie., alternative uses tasks, AUT) in either the "break" condition in which they had to break the walls to move forward in VR, or the "no-break" condition where no barrier walls would appear. Results showed higher AUT originality and AUT fluency in the "break" condition than in the "no-break" condition. Moreover, the effects of "breaking the walls" on AUT originality were fully mediated by cognitive flexibility and persistence. These findings may indicate that enacting metaphors such as "breaking the rules" contribute to creative performance. The enhanced cognitive flexibility and persistence may account for the benefits. Copyright © 2018 Elsevier Inc. All rights reserved.

Moving beyond traditional fire management practices to better minimize community vulnerability to wildfire in southern California

NASA Astrophysics Data System (ADS)

Syphard, A. D.; Keeley, J. E.; Brennan, T. J.

2010-12-01

Wildfires are an important natural process in southern California, but they also present a major hazard for human life and property. The region leads the nation in fire-related losses, and since 2001, wildfires have damaged or destroyed more than 10,000 homes. As human ignitions have increased along with urban development and population growth, fire frequency has also surged, and most home losses occur in large fires when ignitions coincide with Santa Ana windstorms. As the region accommodates more growth in the future, the wildfire threat promises to continue. We will thus explore how a broader, more comprehensive approach to fire management could improve upon traditional approaches for reducing community vulnerability. The traditional approach to mitigating fire risk, in addition to fire suppression, has been to reduce fuel through construction of fuel breaks. Despite increasing expenditure on these treatments, there has been little empirical study of their role in controlling large fires. We will present the results of a study in which we constructed and analyzed a spatial database of fuel breaks in southern California national forests. Our objective was to better understand characteristics of fuel breaks that affect the behavior of large fires and to map where fires and fuel breaks most commonly intersect. We found that fires stopped at fuel breaks 22-47% of the time, depending on the forest, and the reason fires stopped was invariably related to firefighter access and management activities. Fire weather and fuel break condition were also important. The study illustrates the importance of strategic location of fuel breaks because they have been most effective where they provided access for firefighting activities. While fuel breaks have played a role in controlling wildfires at the Wildland Urban Interface, we are evaluating alternative approaches for reducing community vulnerability, including land use planning. Recent research shows that the amount and spatial arrangement of human infrastructure, such as roads and housing developments, strongly influences wildfire patterns. Therefore, we hypothesize that the spatial arrangement and location of housing development is likely to affect the susceptibility of lives and property to fire. In other words, potential for urban loss may be greatest at specific housing densities, spatial patterns of development, and locations of development. If these risk factors can be identified, mapped, and modeled, it is possible that vulnerability to wildfire could be substantially minimized through careful planning for future development - especially because future development will likely increase the region’s fire risk. To address these possibilities, we are evaluating past housing loss in relation to land use planning, in conjunction with other variables that influence fire patterns. We are also exploring alternative future scenarios to identify optimum land use planning strategies for minimizing fire risk.

Stop and revive? The effectiveness of nap and active rest breaks for reducing driver sleepiness.

PubMed

Watling, Christopher N; Smith, Simon S; Horswill, Mark S

2014-11-01

The purpose of this study was to compare the effects of two commonly utilized sleepiness countermeasures: a nap break and an active rest break. The effects of the countermeasures were evaluated by physiological (EEG), subjective, and driving performance measures. Participants completed 2 h of simulated driving, followed by a 15-min nap break or a 15-min active rest break, then completed the final hour of simulated driving. The nap break reduced EEG and subjective sleepiness. The active rest break did not reduce EEG sleepiness, with sleepiness levels eventually increasing, and resulted in an immediate reduction of subjective sleepiness. No difference was found between the two breaks for the driving performance measure. The immediate reduction of subjective sleepiness after the active rest break could leave drivers with erroneous perceptions of their sleepiness, particularly with increases of physiological sleepiness after the break. Copyright © 2014 Society for Psychophysiological Research.

A Methodology for Modeling the Flow of Military Personnel Across Air Force Active and Reserve Components

DTIC Science & Technology

2016-01-01

user, the model will use surplus inventory in one category to fill shortfalls in other categories. The TFBL model also has the capability to allow...the total force. As shown in Table 2.1, we used five-character AFSCs (four digits plus the suffix) to break out pilots in the current force as...Training Unit 4th digit Suffix 4th digit Suffix 4th digit 4th digit 2 or 3 Matches a specific aircraft designation 3 Does not match a specific

Breaking a virus: Identifying molecular level failure modes of a viral capsid by multiscale modeling

NASA Astrophysics Data System (ADS)

Krishnamani, V.; Globisch, C.; Peter, C.; Deserno, M.

2016-10-01

We use coarse-grained (CG) simulations to study the deformation of empty Cowpea Chlorotic Mottle Virus (CCMV) capsids under uniaxial compression, from the initial elastic response up to capsid breakage. Our CG model is based on the MARTINI force field and has been amended by a stabilizing elastic network, acting only within individual proteins, that was tuned to capture the fluctuation spectrum of capsid protein dimers, obtained from all atom simulations. We have previously shown that this model predicts force-compression curves that match AFM indentation experiments on empty CCMV capsids. Here we investigate details of the actual breaking events when the CCMV capsid finally fails. We present a symmetry classification of all relevant protein contacts and show that they differ significantly in terms of stability. Specifically, we show that interfaces which break readily are precisely those which are believed to form last during assembly, even though some of them might share the same contacts as other non-breaking interfaces. In particular, the interfaces that form pentamers of dimers never break, while the virtually identical interfaces within hexamers of dimers readily do. Since these units differ in the large-scale geometry and, most noticeably, the cone-angle at the center of the 5- or 6-fold vertex, we propose that the hexameric unit fails because it is pre-stressed. This not only suggests that hexamers of dimers form less frequently during the early stages of assembly; it also offers a natural explanation for the well-known β-barrel motif at the hexameric center as a post-aggregation stabilization mechanism. Finally, we identify those amino acid contacts within all key protein interfaces that are most persistent during compressive deformation of the capsid, thereby providing potential targets for mutation studies aiming to elucidate the key contacts upon which overall stability rests.

REM sleep deprivation produces a motivational deficit for food reward that is reversed by intra-accumbens amphetamine in rats

PubMed Central

Hanlon, Erin C.; Benca, Ruth M.; Baldo, Brian A.; Kelley, Ann E.

2010-01-01

Prolonged sleep deprivation in rats produces a characteristic syndrome of increase in food intake accompanied by, paradoxically, decrease in weight, suggesting a potential alteration in motivation for food reward. Using the multiple platform method to produce REM sleep deprivation (REMSD), we investigated the effect of REMSD on motivation for food reinforcement with a progressive ratio operant task, which yields a measure of the motor effort that a hungry animal is willing to expend to obtain food (the point at which the animal quits responding is termed the “break-point”). We found that REMSD rats decreased the break-point for sucrose pellet reinforcement in comparison to controls, as revealed by a within-session decline in responding. This behavioral deficit is similar to that observed in rats with diminished dopamine transmission within the nucleus accumbens (Acb), and, considering that stimulants are frequently used in the clinical setting to reverse the effects of sleepiness, we examined the effect of systemic or intra-Acb amphetamine on break-point in REMSD rats. Animals were given either systemic or intra-Acb amphetamine injections on days 3 and 5 of REMSD. Systemic amphetamine (0.1, 0.5, or 2.5 mg/kg) did not increase break point in REMSD rats. In contrast, intra-Acb infusions of amphetamine (1, 10, or 30 µg/ 0.5 µl bilaterally) reversed the REMSD-induced suppression of progressive ratio responding. Specifically, the two higher doses of intra-Acb amphetamine were able to prolong responding within the session (resulting in an increased break-point) on day 3 of REMSD while only the highest dose was sufficient following 5 days of REMSD. These data suggest that decreased motivation for food reward caused by REMSD may result from a suppression of dopamine function in the Acb. PMID:20619322

REM sleep deprivation produces a motivational deficit for food reward that is reversed by intra-accumbens amphetamine in rats.

PubMed

Hanlon, Erin C; Benca, Ruth M; Baldo, Brian A; Kelley, Ann E

2010-10-30

Prolonged sleep deprivation in rats produces a characteristic syndrome of increase in food intake accompanied by, paradoxically, decrease in weight, suggesting a potential alteration in motivation for food reward. Using the multiple platform method to produce REM sleep deprivation (REMSD), we investigated the effect of REMSD on motivation for food reinforcement with a progressive ratio operant task, which yields a measure of the motor effort that a hungry animal is willing to expend to obtain food (the point at which the animal quits responding is termed the "break-point"). We found that REMSD rats decreased the break point for sucrose pellet reinforcement in comparison to controls, as revealed by a within-session decline in responding. This behavioral deficit is similar to that observed in rats with diminished dopamine transmission within the nucleus accumbens (Acb), and, considering that stimulants are frequently used in the clinical setting to reverse the effects of sleepiness, we examined the effect of systemic or intra-Acb amphetamine on break point in REMSD rats. Animals were given either systemic or intra-Acb amphetamine injections on days 3 and 5 of REMSD. Systemic amphetamine (0.1, 0.5, or 2.5mg/kg) did not increase break point in REMSD rats. In contrast, intra-Acb infusions of amphetamine (1, 10, or 30μg/0.5μl bilaterally) reversed the REMSD-induced suppression of progressive ratio responding. Specifically, the two higher doses of intra-Acb amphetamine were able to prolong responding within the session (resulting in an increased break point) on day 3 of REMSD while only the highest dose was sufficient following 5 days of REMSD. These data suggest that decreased motivation for food reward caused by REMSD may result from a suppression of dopamine function in the Acb. Copyright © 2010 Elsevier Inc. All rights reserved.

Break-even analysis of costs for controlling Toxoplasma gondii infections in slaughter pigs via a serological surveillance program in the Netherlands.

PubMed

van Asseldonk, M; van Wagenberg, C P A; Wisselink, H J

2017-03-01

Toxoplasma gondii (T. gondii) is a food safety hazard which causes a substantial human disease burden and cost-of-illness. Infected pig meat is a common source of toxoplasmosis. A break-even analysis was conducted to estimate the point for which the intervention cost at fattening pig farms equaled the cost of averted human disease burden and cost-of-illness minus the costs of a T. gondii surveillance program. The surveillance program comprised serological testing of blood samples taken at slaughter. Break-even points were determined given alternative levels of the effectiveness of the intervention program (10% up to 90% in steps of 10%), the value of an averted DALY (20,000, 50,000 and 80,000 Euro), and threshold of sample prevalence for a farm to be under intervention (5% up to 50% out of 20 samples in steps of 5%). Since test characteristics are a determining factor in the break-even analysis, and literature is inconclusive concerning sensitivity (se) and specificity (sp) of the serological test kit used, two alternative sets of assumptions were analysed. The estimated maximum costs of an intervention if only benefits for domestic consumers were accounted amounted approximately 2981 Euro (se=98.9% and sp=92.7%) versus 4389 Euro (se=65.2% and sp=97.4%) per year per fattening pig farm under intervention assuming an effectiveness of 50%, 50,000 Euro per averted DALY and threshold T. gondii sample prevalence of 5% for a farm to be under intervention. Since almost 80% of the gross domestic production is exported corresponding break-even values increased up to 12,034 Euro and 18,366 Euro if benefits for consumers abroad were included as well. Empirical research to strengthen the knowledge about the efficacy of a farm intervention measures is recommended. Copyright © 2017 Elsevier B.V. All rights reserved.

Bovine immunity - a driver for diversity in Theileria parasites?

PubMed

McKeever, Declan J

2009-06-01

Theileria parva and Theileria annulata are tick-borne parasites of cattle that infect and transform leukocytes, causing severe and often fatal parasitic leukoses. Both species provoke strong immunity against subsequent infection. However, considerable diversity is observed in field populations of each parasite and protection is only assured against homologous challenge. The life cycles of these parasites are complex and involve prolonged exposure to host and vector defence mechanisms. Although the relevant vector mechanisms are poorly defined, protective responses of cattle seem to be tightly focused and variable in their specificity between individuals. This review considers whether bovine immunity acts as a driver for diversity in T. parva and T. annulata and explores other factors that might underlie genetic variation in these parasites.

Preliminary Support for a Generalized Arousal Model of Political Conservatism

PubMed Central

Tritt, Shona M.; Inzlicht, Michael; Peterson, Jordan B.

2013-01-01

It is widely held that negative emotions such as threat, anxiety, and disgust represent the core psychological factors that enhance conservative political beliefs. We put forward an alternative hypothesis: that conservatism is fundamentally motivated by arousal, and that, in this context, the effect of negative emotion is due to engaging intensely arousing states. Here we show that study participants agreed more with right but not left-wing political speeches after being exposed to positive as well as negative emotion-inducing film-clips. No such effect emerged for neutral-content videos. A follow-up study replicated and extended this effect. These results are consistent with the idea that emotional arousal, in general, and not negative valence, specifically, may underlie political conservatism. PMID:24376687

Clinical applications of advanced magnetic resonance imaging techniques for arthritis evaluation

PubMed Central

Martín Noguerol, Teodoro; Luna, Antonio; Gómez Cabrera, Marta; Riofrio, Alexie D

2017-01-01

Magnetic resonance imaging (MRI) has allowed a comprehensive evaluation of articular disease, increasing the detection of early cartilage involvement, bone erosions, and edema in soft tissue and bone marrow compared to other imaging techniques. In the era of functional imaging, new advanced MRI sequences are being successfully applied for articular evaluation in cases of inflammatory, infectious, and degenerative arthropathies. Diffusion weighted imaging, new fat suppression techniques such as DIXON, dynamic contrast enhanced-MRI, and specific T2 mapping cartilage sequences allow a better understanding of the physiopathological processes that underlie these different arthropathies. They provide valuable quantitative information that aids in their differentiation and can be used as potential biomarkers of articular disease course and treatment response. PMID:28979849

The Neural Correlates of Race

PubMed Central

Ito, Tiffany A.; Bartholow, Bruce D.

2009-01-01

Behavioral analyses are a natural choice for understanding the wide-ranging behavioral consequences of racial stereotyping and prejudice. However, neuroimaging and electrophysiological research has recently considered the neural mechanisms that underlie racial categorization and the activation and application of racial stereotypes and prejudice, revealing exciting new insights. Work reviewed here points to the importance of neural structures previously associated with face processing, semantic knowledge activation, evaluation, and self-regulatory behavioral control, allowing for the specification of a neural model of race processing. We show how research on the neural correlates of race can serve to link otherwise disparate lines of evidence on the neural underpinnings of a broad array of social-cognitive phenomena, and consider implications for effecting change in race relations. PMID:19896410